MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Midrin® may be confused with midodrine, Mydfrin®
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
U.S. BRAND NAMES — Amidrine [DSC]; Duradrin® [DSC]; Epidrin; Midrin®; Migquin [DSC]; Migratine; Migrazone® [DSC]; Migrin-A [DSC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
DOSING: ADULTS
Migraine headache: Oral: 2 capsules to start, followed by 1 capsule every hour until relief is obtained (maximum: 5 capsules/12 hours)
Tension headache: Oral: 1-2 capsules every 4 hours (maximum: 8 capsules/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: Acetaminophen 325 mg, isometheptene mucate 65 mg, dichloralphenazone 100 mg [DSC]
Amidrine [DSC], Duradrin® [DSC], Epidrin, Midrin®, Migquin [DSC], Migrazone® [DSC], Migratine, Migrin-A [DSC]: Acetaminophen 325 mg, isometheptene mucate 65 mg, and dichloralphenazone 100 mg
DOSAGE FORMS: CONCISE
Capsule:
Epidrin, Midrin®, Migratine: Acetaminophen 325 mg, isometheptene 65 mg, and dichloralphenazone 100 mg
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Relief of migraine and tension headache
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Central nervous system: Dizziness (transient)
Dermatological: Rash
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, isometheptene, dichloralphenazone, or any component of the formulation; glaucoma; severe renal disease; hypertension; organic heart disease; hepatic disease; MAO inhibitor therapy
RESTRICTIONS — C-IV
METABOLISM / TRANSPORT EFFECTS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
DRUG INTERACTIONS
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Beta-Blockers: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Risk D: Consider therapy modification
Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Primarily with oral administration of phenylephrine. Risk D: Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
LACTATION — Excretion in breast milk unknown/use caution
BREAST-FEEDING CONSIDERATIONS — Acetaminophen and dichloralphenazone are excreted in breast milk; excretion of isometheptene is not known.
PRICING — (data from drugstore.com)
Capsules (Epidrin)
325-65-100 mg (100): $63.99
Capsules (Isometheptene-APAP-Dichloral)
65-325-100 mg (30): $22.99
Capsules (Migratine)
325-65-100 mg (100): $37.57
Showing posts with label Acetaminophen. Show all posts
Showing posts with label Acetaminophen. Show all posts
Monday, May 17, 2010
Acetaminophen, diphenhydramine, and phenylephrine
MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Benadryl® Allergy and Cold [OTC]; Benadryl® Allergy and Sinus Headache [OTC]; Benadry® Maximum Strength Severe Allergy and Sinus Headache [OTC]; Cold Control PE [OTC]; Sudafed PE® Nighttime Cold [OTC]; Sudafed PE® Severe Cold [OTC]; Theraflu® Nighttime Severe Cold & Cough [OTC]; Theraflu® Sugar-Free Nighttime Severe Cold & Cough [OTC]; Theraflu® Warming Relief Flu & Sore Throat [OTC]; Theraflu® Warming Relief Nighttime Severe Cold & Cough [OTC]; Tylenol® Allergy Multi-Symptom Nighttime [OTC]; Tylenol® Children's Plus Cold and Allergy [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Decongestant
Histamine H1 Antagonist
DOSING: ADULTS — Hay fever/cold symptoms: Oral: General dosing guidelines; refer to specific product labeling (Benadryl® Allergy and Cold, Benadryl® Allergy and Sinus Headache, Sudafed PE® Nighttime Cold, Sudafed PE® Severe Cold, Tylenol® Allergy Multi-Symptom Nighttime): Two caplets every 4 hours as needed; maximum: 12 caplets/24 hours
DOSING: PEDIATRIC — Hay fever/cold symptoms: Oral: General dosing guidelines; refer to specific product labeling:
Children 6-11 years (Benadryl® Allergy and Cold, Benadryl® Allergy and Sinus Headache, Sudafed PE® Severe Cold): One caplet every 4 hours as needed; maximum: 5 caplets/24 hours
Children 6-11 years; 48-95 lbs (Tylenol® Children's Plus Cold and Allergy): 10 mL every 4 hours as needed; maximum: 5 doses/24 hours
Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:
Benadryl® Allergy and Cold, Benadryl® Allergy and Sinus Headache, Sudafed PE® Severe Cold: Acetaminophen 325 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 5 mg
Benadry® Maximum Strength Severe Allergy and Sinus Headache: Acetaminophen 325 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 5 mg
Cold Control PE: Acetaminophen 650 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 10 mg
Sudafed PE® Nighttime Cold: Acetaminophen 325 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 5 mg
Tylenol® Allergy Multi-Symptom Nighttime: Acetaminophen 325 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Liquid:
Tylenol® Children's Plus Cold and Allergy: Acetaminophen 160 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (120 mL) [contains sodium benzoate; bubble gum flavor]
Powder for solution, oral:
Theraflu® Nighttime Severe Cold & Cough: Acetaminophen 650 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [contains phenylalanine 13 mg, potassium 10 mg, and sodium 23 mg per packet; honey lemon flavor]
Theraflu® Sugar-Free Nighttime Severe Cold & Cough: Acetaminophen 650 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [sugar free; contains phenylalanine 13 mg, potassium 10 mg, and sodium 23 mg per packet; honey lemon flavor]
Syrup, oral:
Theraflu® Warming Relief Flu & Sore Throat: Acetaminophen 325 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol, potassium 5 mg/15 mL, propylene glycol, sodium 5 mg/15 mL, sodium benzoate; cherry flavor]
Theraflu® Warming Relief Nighttime Severe Cold & Cough: Acetaminophen 325 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol 10%, potassium 5 mg/15 mL, propylene glycol, sodium 5 mg/15 mL, sodium benzoate; cherry flavor]
DOSAGE FORMS: CONCISE
Caplet:
Benadryl® Allergy and Cold [OTC], Benadryl® Allergy and Sinus Headache [OTC], Sudafed PE® Severe Cold [OTC]: Acetaminophen 325 mg, diphenhydramine 12.5 mg, and phenylephrine 5 mg
Benadry® Maximum Strength Severe Allergy and Sinus Headache, Sudafed PE® Nighttime Cold [OTC], Tylenol® Allergy Multi-Symptom Nighttime [OTC]: Acetaminophen 325 mg, diphenhydramine 25 mg, and phenylephrine 5 mg
Cold Control PE: Acetaminophen 650 mg, diphenhydramine 25 mg, and phenylephrine 10 mg
Liquid:
Tylenol® Children's Plus Cold and Allergy [OTC]: Acetaminophen 160 mg, diphenhydramine 12.5 mg, and phenylephrine 2.5 mg per 5 mL
Powder for solution, oral:
Theraflu® Nighttime Severe Cold & Cough [OTC], Theraflu® Sugar-Free Nighttime Severe Cold & Cough [OTC]: Acetaminophen 650 mg, diphenhydramine 25 mg, and phenylephrine 10 mg per packet (6s)
Syrup, oral:
Theraflu® Warming Relief Flu & Sore Throat [OTC], Theraflu® Warming Relief Nighttime Severe Cold & Cough [OTC]: Acetaminophen 325 mg, diphenhydramine 12.5 mg, and phenylephrine 5 mg per 15 mL (245.5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to meals.
Liquid: Shake well before use. Only use enclosed dosing cup; do not use other devices.
Tylenol® Allergy Multi-Symptom Nighttime: Swallow whole; do not crush, chew, or dissolve.
USE — Temporary relief of symptoms of hay fever and the common cold, including sinus/nasal congestion and pain/pressure, headache, sneezing, runny nose, itchy/watery eyes, sore throat, cough, and minor aches and pains
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use with or within 14 days of MAO inhibitor therapy; concurrent use with other products containing acetaminophen, diphenhydramine (including topical) or phenylephrine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days in adults (or >5 days in children) during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult healthcare provider. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk D: Consider therapy modification
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
DIETARY CONSIDERATIONS — Theraflu® Nighttime Severe Cold & Cough, Theraflu® Sugar-Free Nighttime Severe Cold & Cough: Powder for oral solution contains: Phenylalanine 13 mg per packet and sodium 23 mg per packet
MECHANISM OF ACTION
Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation.
Diphenhydramine is an H1-receptor antagonist.
Phenylephrine causes vasoconstriction of the arterioles of the nasal mucosa.
PHARMACODYNAMICS / KINETICS — See individual agents.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Benadryl® Allergy and Cold [OTC]; Benadryl® Allergy and Sinus Headache [OTC]; Benadry® Maximum Strength Severe Allergy and Sinus Headache [OTC]; Cold Control PE [OTC]; Sudafed PE® Nighttime Cold [OTC]; Sudafed PE® Severe Cold [OTC]; Theraflu® Nighttime Severe Cold & Cough [OTC]; Theraflu® Sugar-Free Nighttime Severe Cold & Cough [OTC]; Theraflu® Warming Relief Flu & Sore Throat [OTC]; Theraflu® Warming Relief Nighttime Severe Cold & Cough [OTC]; Tylenol® Allergy Multi-Symptom Nighttime [OTC]; Tylenol® Children's Plus Cold and Allergy [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Decongestant
Histamine H1 Antagonist
DOSING: ADULTS — Hay fever/cold symptoms: Oral: General dosing guidelines; refer to specific product labeling (Benadryl® Allergy and Cold, Benadryl® Allergy and Sinus Headache, Sudafed PE® Nighttime Cold, Sudafed PE® Severe Cold, Tylenol® Allergy Multi-Symptom Nighttime): Two caplets every 4 hours as needed; maximum: 12 caplets/24 hours
DOSING: PEDIATRIC — Hay fever/cold symptoms: Oral: General dosing guidelines; refer to specific product labeling:
Children 6-11 years (Benadryl® Allergy and Cold, Benadryl® Allergy and Sinus Headache, Sudafed PE® Severe Cold): One caplet every 4 hours as needed; maximum: 5 caplets/24 hours
Children 6-11 years; 48-95 lbs (Tylenol® Children's Plus Cold and Allergy): 10 mL every 4 hours as needed; maximum: 5 doses/24 hours
Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:
Benadryl® Allergy and Cold, Benadryl® Allergy and Sinus Headache, Sudafed PE® Severe Cold: Acetaminophen 325 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 5 mg
Benadry® Maximum Strength Severe Allergy and Sinus Headache: Acetaminophen 325 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 5 mg
Cold Control PE: Acetaminophen 650 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 10 mg
Sudafed PE® Nighttime Cold: Acetaminophen 325 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 5 mg
Tylenol® Allergy Multi-Symptom Nighttime: Acetaminophen 325 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Liquid:
Tylenol® Children's Plus Cold and Allergy: Acetaminophen 160 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (120 mL) [contains sodium benzoate; bubble gum flavor]
Powder for solution, oral:
Theraflu® Nighttime Severe Cold & Cough: Acetaminophen 650 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [contains phenylalanine 13 mg, potassium 10 mg, and sodium 23 mg per packet; honey lemon flavor]
Theraflu® Sugar-Free Nighttime Severe Cold & Cough: Acetaminophen 650 mg, diphenhydramine hydrochloride 25 mg, and phenylephrine hydrochloride 10 mg per packet (6s) [sugar free; contains phenylalanine 13 mg, potassium 10 mg, and sodium 23 mg per packet; honey lemon flavor]
Syrup, oral:
Theraflu® Warming Relief Flu & Sore Throat: Acetaminophen 325 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol, potassium 5 mg/15 mL, propylene glycol, sodium 5 mg/15 mL, sodium benzoate; cherry flavor]
Theraflu® Warming Relief Nighttime Severe Cold & Cough: Acetaminophen 325 mg, diphenhydramine hydrochloride 12.5 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol 10%, potassium 5 mg/15 mL, propylene glycol, sodium 5 mg/15 mL, sodium benzoate; cherry flavor]
DOSAGE FORMS: CONCISE
Caplet:
Benadryl® Allergy and Cold [OTC], Benadryl® Allergy and Sinus Headache [OTC], Sudafed PE® Severe Cold [OTC]: Acetaminophen 325 mg, diphenhydramine 12.5 mg, and phenylephrine 5 mg
Benadry® Maximum Strength Severe Allergy and Sinus Headache, Sudafed PE® Nighttime Cold [OTC], Tylenol® Allergy Multi-Symptom Nighttime [OTC]: Acetaminophen 325 mg, diphenhydramine 25 mg, and phenylephrine 5 mg
Cold Control PE: Acetaminophen 650 mg, diphenhydramine 25 mg, and phenylephrine 10 mg
Liquid:
Tylenol® Children's Plus Cold and Allergy [OTC]: Acetaminophen 160 mg, diphenhydramine 12.5 mg, and phenylephrine 2.5 mg per 5 mL
Powder for solution, oral:
Theraflu® Nighttime Severe Cold & Cough [OTC], Theraflu® Sugar-Free Nighttime Severe Cold & Cough [OTC]: Acetaminophen 650 mg, diphenhydramine 25 mg, and phenylephrine 10 mg per packet (6s)
Syrup, oral:
Theraflu® Warming Relief Flu & Sore Throat [OTC], Theraflu® Warming Relief Nighttime Severe Cold & Cough [OTC]: Acetaminophen 325 mg, diphenhydramine 12.5 mg, and phenylephrine 5 mg per 15 mL (245.5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to meals.
Liquid: Shake well before use. Only use enclosed dosing cup; do not use other devices.
Tylenol® Allergy Multi-Symptom Nighttime: Swallow whole; do not crush, chew, or dissolve.
USE — Temporary relief of symptoms of hay fever and the common cold, including sinus/nasal congestion and pain/pressure, headache, sneezing, runny nose, itchy/watery eyes, sore throat, cough, and minor aches and pains
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use with or within 14 days of MAO inhibitor therapy; concurrent use with other products containing acetaminophen, diphenhydramine (including topical) or phenylephrine
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days in adults (or >5 days in children) during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult healthcare provider. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk D: Consider therapy modification
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — See individual agents.
DIETARY CONSIDERATIONS — Theraflu® Nighttime Severe Cold & Cough, Theraflu® Sugar-Free Nighttime Severe Cold & Cough: Powder for oral solution contains: Phenylalanine 13 mg per packet and sodium 23 mg per packet
MECHANISM OF ACTION
Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation.
Diphenhydramine is an H1-receptor antagonist.
Phenylephrine causes vasoconstriction of the arterioles of the nasal mucosa.
PHARMACODYNAMICS / KINETICS — See individual agents.
Acetaminophen, dextromethorphan, doxylamine, and pseudoephedrine
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — All-Nite Multi-Symptom Cold/Flu [OTC]; Vicks® NyQuil® D Cold & Flu Multi-Symptom [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Decongestant
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Relief of cold and flu symptoms: Oral: 30 mL every 6 hours (maximum: 120 mL/24 hours)
DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid:
All-Nite Multi-Symptom Cold/Flu: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL (296 mL) [contains sodium 17 mg/15 mL, ethanol 10%, and propylene glycol]
Vicks® NyQuil® D Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL (295 mL) [contains sodium 18 mg/15 mL, ethanol 10%, and propylene glycol]
DOSAGE FORMS: CONCISE
Liquid:
All-Nite Multi-Symptom Cold/Flu [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL
Vicks® NyQuil® D Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer orally; only use enclosed dosing cup or tablespoon to administer; do not use other devices.
USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, congestion, runny nose, sneezing, sore throat)
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use of MAO inhibitors within 14 days, concurrent use with other products containing acetaminophen
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.
Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS
All-Nite Cold contains sodium 17 mg per 15 mL.
Vicks® NyQuil® D Cold & Flu Multi-Symptom contains sodium 18 mg per 15 mL.
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — All-Nite Multi-Symptom Cold/Flu [OTC]; Vicks® NyQuil® D Cold & Flu Multi-Symptom [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Decongestant
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Relief of cold and flu symptoms: Oral: 30 mL every 6 hours (maximum: 120 mL/24 hours)
DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid:
All-Nite Multi-Symptom Cold/Flu: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL (296 mL) [contains sodium 17 mg/15 mL, ethanol 10%, and propylene glycol]
Vicks® NyQuil® D Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL (295 mL) [contains sodium 18 mg/15 mL, ethanol 10%, and propylene glycol]
DOSAGE FORMS: CONCISE
Liquid:
All-Nite Multi-Symptom Cold/Flu [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL
Vicks® NyQuil® D Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, doxylamine succinate 6.25 mg and pseudoephedrine hydrochloride 30 mg per 15 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Administer orally; only use enclosed dosing cup or tablespoon to administer; do not use other devices.
USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, congestion, runny nose, sneezing, sore throat)
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use of MAO inhibitors within 14 days, concurrent use with other products containing acetaminophen
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.
Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS
All-Nite Cold contains sodium 17 mg per 15 mL.
Vicks® NyQuil® D Cold & Flu Multi-Symptom contains sodium 18 mg per 15 mL.
Acetaminophen, dextromethorphan, and phenylephrin
MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Alka-Seltzer Plus® Day Cold [OTC]; Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief [OTC]; Mapap® Multi-Symptom Cold [OTC]; Theraflu® Daytime Severe Cold & Cough [OTC]; Theraflu® Warming Relief Daytime Severe Cold & Cough [OTC]; Tylenol® Cold Head Congestion Daytime [OTC]; Tylenol® Cold Multi-Symptom Daytime [OTC]; Vicks® DayQuil® Cold/Flu Multi-Symptom [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Decongestant
DOSING: ADULTS — Product labeling: Relief of cold and flu symptoms: Oral:
Alka-Seltzer Plus® Day Cold: 2 capsules or 20 mL every 4 hours (maximum: 6 doses/24 hours)
Tylenol® Cold Head Congestion Daytime: 2 caplets every 4 hours (maximum: 6 doses/24 hours)
Tylenol® Cold Multi-Symptom Daytime: 2 caplets/gelcaps or 30 mL every 4 hours (maximum: 6 doses/24 hours)
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief LiquiCaps: 2 capsules every 4 hours (maximum: 6 doses/24 hours)
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief Liquid: 30 mL every 4 hours (maximum: 6 doses/24 hours)
DOSING: PEDIATRIC — Product labeling: Relief of cold and flu symptoms: Oral:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief Liquid:
Children 6-11 years: 15 mL every 4 hours, up to 5 doses/day (maximum: 75 mL/24 hours)
Children ≥ 12 years: Refer to adult dosing.
Alka-Seltzer Plus® Day Cold, Tylenol® Cold Head Congestion Daytime, Tylenol® Cold Multi-Symptom Daytime, Vicks® DayQuil® Cold/Flu Multi-Symptom Relief LiquiCaps: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:
Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Mapap® Multi-Symptom Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Theraflu® Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Tylenol® Cold Head Congestion Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Capsule, liquid gel:
Alka-Seltzer Plus® Day Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Capsule, liquicap:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Gelcap:
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Liquid:
Alka-Seltzer Plus® Day Cold: Acetaminophen 162.5 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (180 mL) [alcohol free; contains sodium 3 mg/5 mL, propylene glycol, and sodium benzoate; berry flavor]
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (240 mL) [contains sodium 5 mg/15 mL, sodium benzoate, and propylene glycol; Citrus Burst™ flavor]
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (180 mL, 300 mL) [contains sodium 71 mg/15 mL and propylene glycol]
Powder for solution:
Theraflu® Daytime Severe Cold & Cough: Acetaminophen 650 mg, dextromethorphan 20 mg, and phenylephrine hydrochloride 10 mg/packet (6s) [contains phenylalanine 14 mg, potassium 10 mg, and sodium 20 mg/packet; berry flavor]
Syrup:
Theraflu® Warming Relief Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol, propylene glycol, sodium 8 mg/15 mL, sodium benzoate; cherry flavor]
DOSAGE FORMS: CONCISE
Caplet:
Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief [OTC], Mapap® Multi-Symptom Cold [OTC], Theraflu® Daytime Severe Cold & Cough [OTC], Tylenol® Cold Head Congestion Daytime [OTC], Tylenol® Cold Multi-Symptom Daytime [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Capsule, liquid gel:
Alka-Seltzer Plus® Day Cold [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Capsule, liquicap:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Gelcap:
Tylenol® Cold Multi-Symptom Daytime [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Liquid:
Alka-Seltzer Plus® Day Cold [OTC]: Acetaminophen 162.5 mg, dextromethorphan 5 mg, and phenylephrine 2.5 mg per 5 mL
Tylenol® Cold Multi-Symptom Daytime [OTC], Vicks® DayQuil® Cold/Flu Multi-Symptom Relief [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg per 15 mL
Powder for solution:
Theraflu® Daytime Severe Cold & Cough [OTC]: Acetaminophen 650 mg, dextromethorphan 20 mg, and phenylephrine 10 mg/packet (6s)
Syrup:
Theraflu® Warming Relief Daytime Severe Cold & Cough [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg per 15 mL
GENERIC EQUIVALENT AVAILABLE — Yes: Caplet
ADMINISTRATION — Solid dosage forms should be swallowed whole; do not crush, chew or dissolve. Administer liquid capsule formulations with water.
USE — Temporary relief of common cold and flu symptoms (eg, pain, fever, cough, congestion)
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, dextromethorphan, phenylephrine, or any component of the formulation; use of MAO inhibitors within 14 days
WARNINGS / PRECAUTIONS
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Special populations: Elderly: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics. Pediatrics: Use with caution in children; do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.
Dosage form specific issues: Phenylalanine: Some products may contain phenylalanine. Sodium: Some products may contain sodium; use with caution in sodium restricted patients.
Other warnings/precautions: OTC labeling: Patients with hypertension, hyperthyroidism, diabetes mellitus, glaucoma, cardiovascular disease, or prostatic hyperplasia should consult a physician prior to use. Patients with chronic cough (associated with COPD or smoking) and/or productive cough (eg, copious amounts of phlegm) should be evaluated by a healthcare provider prior to use. Products containing acetaminophen are not recommended in patients consuming ≥ 3 alcoholic beverages/day; consult a physician. If pain, nasal congestion, or cough increases in severity or persists >7 days in adults (or >5 days in children) during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. Do not use in children <2 years of age.
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Dextromethorphan: Substrate of CYP2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)
DRUG INTERACTIONS
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS
Alka-Seltzer Plus® Day Cold liquid contains sodium 3 mg per 5 mL.
Theraflu® Daytime Severe Cold & Cough (powder for solution) contains phenylalanine 14 mg and sodium 20 mg per packet.
Theraflu® Warming Relief Daytime Severe Cold & Cough syrup contains sodium 8 mg per 15 mL.
Tylenol® Cold Multi-Symptom Daytime liquid contains sodium 5 mg per 15 mL.
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief liquid contains sodium 71 mg per 15 mL.
INTERNATIONAL BRAND NAMES — Tusedex (PH)
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Alka-Seltzer Plus® Day Cold [OTC]; Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief [OTC]; Mapap® Multi-Symptom Cold [OTC]; Theraflu® Daytime Severe Cold & Cough [OTC]; Theraflu® Warming Relief Daytime Severe Cold & Cough [OTC]; Tylenol® Cold Head Congestion Daytime [OTC]; Tylenol® Cold Multi-Symptom Daytime [OTC]; Vicks® DayQuil® Cold/Flu Multi-Symptom [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Decongestant
DOSING: ADULTS — Product labeling: Relief of cold and flu symptoms: Oral:
Alka-Seltzer Plus® Day Cold: 2 capsules or 20 mL every 4 hours (maximum: 6 doses/24 hours)
Tylenol® Cold Head Congestion Daytime: 2 caplets every 4 hours (maximum: 6 doses/24 hours)
Tylenol® Cold Multi-Symptom Daytime: 2 caplets/gelcaps or 30 mL every 4 hours (maximum: 6 doses/24 hours)
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief LiquiCaps: 2 capsules every 4 hours (maximum: 6 doses/24 hours)
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief Liquid: 30 mL every 4 hours (maximum: 6 doses/24 hours)
DOSING: PEDIATRIC — Product labeling: Relief of cold and flu symptoms: Oral:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief Liquid:
Children 6-11 years: 15 mL every 4 hours, up to 5 doses/day (maximum: 75 mL/24 hours)
Children ≥ 12 years: Refer to adult dosing.
Alka-Seltzer Plus® Day Cold, Tylenol® Cold Head Congestion Daytime, Tylenol® Cold Multi-Symptom Daytime, Vicks® DayQuil® Cold/Flu Multi-Symptom Relief LiquiCaps: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:
Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Mapap® Multi-Symptom Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Theraflu® Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Tylenol® Cold Head Congestion Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg [Cool Burst™ flavor]
Capsule, liquid gel:
Alka-Seltzer Plus® Day Cold: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Capsule, liquicap:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Gelcap:
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg
Liquid:
Alka-Seltzer Plus® Day Cold: Acetaminophen 162.5 mg, dextromethorphan hydrobromide 5 mg, and phenylephrine hydrochloride 2.5 mg per 5 mL (180 mL) [alcohol free; contains sodium 3 mg/5 mL, propylene glycol, and sodium benzoate; berry flavor]
Tylenol® Cold Multi-Symptom Daytime: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (240 mL) [contains sodium 5 mg/15 mL, sodium benzoate, and propylene glycol; Citrus Burst™ flavor]
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (180 mL, 300 mL) [contains sodium 71 mg/15 mL and propylene glycol]
Powder for solution:
Theraflu® Daytime Severe Cold & Cough: Acetaminophen 650 mg, dextromethorphan 20 mg, and phenylephrine hydrochloride 10 mg/packet (6s) [contains phenylalanine 14 mg, potassium 10 mg, and sodium 20 mg/packet; berry flavor]
Syrup:
Theraflu® Warming Relief Daytime Severe Cold & Cough: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and phenylephrine hydrochloride 5 mg per 15 mL (245.5 mL) [contains ethanol, propylene glycol, sodium 8 mg/15 mL, sodium benzoate; cherry flavor]
DOSAGE FORMS: CONCISE
Caplet:
Comtrex® Maximum Strength, Non-Drowsy Cold & Cough Relief [OTC], Mapap® Multi-Symptom Cold [OTC], Theraflu® Daytime Severe Cold & Cough [OTC], Tylenol® Cold Head Congestion Daytime [OTC], Tylenol® Cold Multi-Symptom Daytime [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Capsule, liquid gel:
Alka-Seltzer Plus® Day Cold [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Capsule, liquicap:
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Gelcap:
Tylenol® Cold Multi-Symptom Daytime [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg
Liquid:
Alka-Seltzer Plus® Day Cold [OTC]: Acetaminophen 162.5 mg, dextromethorphan 5 mg, and phenylephrine 2.5 mg per 5 mL
Tylenol® Cold Multi-Symptom Daytime [OTC], Vicks® DayQuil® Cold/Flu Multi-Symptom Relief [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg per 15 mL
Powder for solution:
Theraflu® Daytime Severe Cold & Cough [OTC]: Acetaminophen 650 mg, dextromethorphan 20 mg, and phenylephrine 10 mg/packet (6s)
Syrup:
Theraflu® Warming Relief Daytime Severe Cold & Cough [OTC]: Acetaminophen 325 mg, dextromethorphan 10 mg, and phenylephrine 5 mg per 15 mL
GENERIC EQUIVALENT AVAILABLE — Yes: Caplet
ADMINISTRATION — Solid dosage forms should be swallowed whole; do not crush, chew or dissolve. Administer liquid capsule formulations with water.
USE — Temporary relief of common cold and flu symptoms (eg, pain, fever, cough, congestion)
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, dextromethorphan, phenylephrine, or any component of the formulation; use of MAO inhibitors within 14 days
WARNINGS / PRECAUTIONS
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Special populations: Elderly: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics. Pediatrics: Use with caution in children; do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician.
Dosage form specific issues: Phenylalanine: Some products may contain phenylalanine. Sodium: Some products may contain sodium; use with caution in sodium restricted patients.
Other warnings/precautions: OTC labeling: Patients with hypertension, hyperthyroidism, diabetes mellitus, glaucoma, cardiovascular disease, or prostatic hyperplasia should consult a physician prior to use. Patients with chronic cough (associated with COPD or smoking) and/or productive cough (eg, copious amounts of phlegm) should be evaluated by a healthcare provider prior to use. Products containing acetaminophen are not recommended in patients consuming ≥ 3 alcoholic beverages/day; consult a physician. If pain, nasal congestion, or cough increases in severity or persists >7 days in adults (or >5 days in children) during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. Do not use in children <2 years of age.
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Dextromethorphan: Substrate of CYP2B6 (minor), 2C9 (minor), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2D6 (weak)
DRUG INTERACTIONS
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS
Alka-Seltzer Plus® Day Cold liquid contains sodium 3 mg per 5 mL.
Theraflu® Daytime Severe Cold & Cough (powder for solution) contains phenylalanine 14 mg and sodium 20 mg per packet.
Theraflu® Warming Relief Daytime Severe Cold & Cough syrup contains sodium 8 mg per 15 mL.
Tylenol® Cold Multi-Symptom Daytime liquid contains sodium 5 mg per 15 mL.
Vicks® DayQuil® Cold/Flu Multi-Symptom Relief liquid contains sodium 71 mg per 15 mL.
INTERNATIONAL BRAND NAMES — Tusedex (PH)
Acetaminophen, codeine, and doxylamine
MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Analgesic, Opioid
Antitussive
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Oral: 1-2 tablets every 4 hours as needed; total dose should not exceed 12 tablets in a 24-hour period
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: HEPATIC IMPAIRMENT
Acetaminophen: Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
Codeine: Dosage adjustment of codeine is probably necessary in hepatic insufficiency; no specific guidelines available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet:
Mersyndol® With Codeine [CAN]: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet:
Mersyndol® With Codeine [CAN]: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg [not available in the U.S.]
USE — Relief of headache, cold symptoms, neuralgia, and muscular aches/pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, doxylamine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension/hypotension and tachycardia). CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Gastrointestinal motility disorders: Use with caution in patients with gastrointestinal motility disorders; avoid in paralytic ileus. Glaucoma: Use with caution in patients with angle-closure glaucoma and/or increased intraocular pressure. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Pyloroduodenal obstruction: Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer). Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children <12 years of age. Surgical patients: Use with caution in postoperative patients following thoracotomy or laparotomy due to suppression of cough.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — CDSA-1; Not available in U.S.
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Codeine: Substrate of CYP2D6 (major), 3A4 (minor); Inhibits CYP2D6 (weak)
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Somatostatin Analogs: May decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Should not be used in pregnancy unless the potential benefit to the mother justifies possible harm to the fetus. Refer to Codeine monograph.
LACTATION — No data available.
BREAST-FEEDING CONSIDERATIONS — Doxylamine may be excreted in breast milk, potentially resulting in sedative effects in nursing infants. Refer to Codeine monograph.
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
CANADIAN BRAND NAMES — Mersyndol® With Codeine
INTERNATIONAL BRAND NAMES — Mersyndol With Codeine (CA)
MECHANISM OF ACTION — Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center. Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Doxylamine competes with histamine for H1-receptor sites on effector cells; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity.
PHARMACODYNAMICS / KINETICS — See individual agents.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Analgesic, Opioid
Antitussive
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Oral: 1-2 tablets every 4 hours as needed; total dose should not exceed 12 tablets in a 24-hour period
DOSING: PEDIATRIC — Children >12 years: Refer to adult dosing.
DOSING: RENAL IMPAIRMENT — No dosage adjustment required.
DOSING: HEPATIC IMPAIRMENT
Acetaminophen: Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
Codeine: Dosage adjustment of codeine is probably necessary in hepatic insufficiency; no specific guidelines available.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Tablet:
Mersyndol® With Codeine [CAN]: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg [not available in the U.S.]
DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name
Tablet:
Mersyndol® With Codeine [CAN]: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg [not available in the U.S.]
USE — Relief of headache, cold symptoms, neuralgia, and muscular aches/pain
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, codeine, doxylamine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension/hypotension and tachycardia). CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Gastrointestinal motility disorders: Use with caution in patients with gastrointestinal motility disorders; avoid in paralytic ileus. Glaucoma: Use with caution in patients with angle-closure glaucoma and/or increased intraocular pressure. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Pyloroduodenal obstruction: Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer). Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children <12 years of age. Surgical patients: Use with caution in postoperative patients following thoracotomy or laparotomy due to suppression of cough.
Other warnings/precautions: Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — CDSA-1; Not available in U.S.
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Codeine: Substrate of CYP2D6 (major), 3A4 (minor); Inhibits CYP2D6 (weak)
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Somatostatin Analogs: May decrease the metabolism of Codeine. The formation of two major codeine metabolites (morphine and norcodeine) may be impaired by somatostatin analogs. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
PREGNANCY IMPLICATIONS — There are no adequate and well-controlled studies in pregnant women. Should not be used in pregnancy unless the potential benefit to the mother justifies possible harm to the fetus. Refer to Codeine monograph.
LACTATION — No data available.
BREAST-FEEDING CONSIDERATIONS — Doxylamine may be excreted in breast milk, potentially resulting in sedative effects in nursing infants. Refer to Codeine monograph.
MONITORING PARAMETERS — Relief of pain, respiratory and mental status, blood pressure, bowel function
CANADIAN BRAND NAMES — Mersyndol® With Codeine
INTERNATIONAL BRAND NAMES — Mersyndol With Codeine (CA)
MECHANISM OF ACTION — Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center. Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Doxylamine competes with histamine for H1-receptor sites on effector cells; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity.
PHARMACODYNAMICS / KINETICS — See individual agents.
Acetaminophen, dextromethorphan, and doxylamine
MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — All-Nite [OTC]; Tylenol® Cough & Sore Throat Nighttime [OTC]; Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Relief of cold and flu symptoms: Oral: Two capsules/caplets or 30 mL every 6 hours (maximum: 8 capsules or 240 mL/24 hours)
DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg [contains vitamin C]
Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg
Liquid:
All-Nite: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (177 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; cherry flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; Cool Burst™ flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; honey lemon flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; original flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 19 mg/15 mL, ethanol, and propylene glycol; cherry flavor]
DOSAGE FORMS: CONCISE
Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg dextromethorphan 15 mg, and doxylamine 6.25 mg
Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg
Liquid:
All-Nite [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Tylenol® Cough & Sore Throat Nighttime [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Liquid: Only use enclosed dosing cup or tablespoon to administer; do not use other devices.
USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, runny nose, sneezing, sore throat)
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use of MAO inhibitors within 14 days; concurrent use with other products containing acetaminophen; pediatric sedation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician. Do not use in children <4 years of age.
Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS
All-Nite contains sodium 18 mg per 15 mL.
Tylenol® Cough & Sore Throat Nighttime contains sodium 11 mg per 15 mL.
Vicks® NyQuil® Cold & Flu Multi-Symptom liquid contains sodium 18 mg per 15 mL (original flavor) or 19 mg per 15 mL (cherry flavor).
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — All-Nite [OTC]; Tylenol® Cough & Sore Throat Nighttime [OTC]; Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]
PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous
Antitussive
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Relief of cold and flu symptoms: Oral: Two capsules/caplets or 30 mL every 6 hours (maximum: 8 capsules or 240 mL/24 hours)
DOSING: PEDIATRIC — Relief of cold and flu symptoms: Oral: Children ≥ 12 years: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg [contains vitamin C]
Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg
Liquid:
All-Nite: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (177 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; cherry flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; Cool Burst™ flavor]
Tylenol® Cough & Sore Throat Nighttime: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (240 mL) [contains sodium 11 mg/15 mL, propylene glycol, and sodium benzoate; honey lemon flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 18 mg/15 mL, ethanol, and propylene glycol; original flavor]
Vicks® NyQuil® Cold & Flu Multi-Symptom: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL (180 mL, 300 mL, 360 mL) [contains sodium 19 mg/15 mL, ethanol, and propylene glycol; cherry flavor]
DOSAGE FORMS: CONCISE
Caplet:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg dextromethorphan 15 mg, and doxylamine 6.25 mg
Capsule, liquicap:
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg
Liquid:
All-Nite [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Tylenol® Cough & Sore Throat Nighttime [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and doxylamine 6.25 mg per 15 mL
Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and doxylamine succinate 6.25 mg per 15 mL
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION — Liquid: Only use enclosed dosing cup or tablespoon to administer; do not use other devices.
USE — Temporary relief of common cold and flu symptoms (eg, minor aches and pain, fever, cough, runny nose, sneezing, sore throat)
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use of MAO inhibitors within 14 days; concurrent use with other products containing acetaminophen; pediatric sedation
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations exist on OTC labeling for patient's age, the product should not be administered without the guidance of a physician. Do not use in children <4 years of age.
Dosage form specific issues: Sodium: Some products may contain sodium; use with caution in sodium-restricted patients.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days during use, consult a physician. If redness, swelling, or rash occurs or if fever worsens or persists >3 days during therapy, consult a physician. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or last >2 days, discontinue use and consult healthcare provider.
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QuiNIDine: May decrease the metabolism of Dextromethorphan. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the adverse/toxic effect of Dextromethorphan. Exceptions: Fluvoxamine. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
DIETARY CONSIDERATIONS
All-Nite contains sodium 18 mg per 15 mL.
Tylenol® Cough & Sore Throat Nighttime contains sodium 11 mg per 15 mL.
Vicks® NyQuil® Cold & Flu Multi-Symptom liquid contains sodium 18 mg per 15 mL (original flavor) or 19 mg per 15 mL (cherry flavor).
Acetaminophen, chlorpheniramine, and pseudoephedrine
MEDICATION SAFETY ISSUES
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Drinex [OTC]; Relief-SF®
PHARMACOLOGIC CATEGORY
Alpha/Beta Agonist
Analgesic, Miscellaneous
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Relief of cold, allergy, and sinus symptoms: Oral: Product labeling:
Drinex: 1 tablet 3-4 times/day (maximum: 4 tablets/24 hours); do not take for >7 days
Relief-SF®: 1-2 caplets every 6 hours (maximum: 8 caplets/24 hours)
DOSING: PEDIATRIC
Relief of cold, allergy, and sinus symptoms: Oral: Children ≥ 12 years of age: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Relief-SF®: Acetaminophen 500 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Tablet:
Drinex: Acetaminophen 650 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE
Caplet: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Relief-SF®: Acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Tablet:
Drinex [OTC]: Acetaminophen 650 mg, chlorpheniramine 4 mg, and pseudoephedrine 60 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Temporary relief of cold, allergy, or sinus symptoms
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use of MAO inhibitors within 14 days; concurrent use with other products containing acetaminophen
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression which may impair physical or mental abilities; patients must be cautioned about performing tasks which require metal alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Elderly: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics. Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations for patient's age exist on OTC labeling, the product should not be administered without the guidance of a physician.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days in adults (>5 days in children) during use, consult a physician. If redness, swelling, or rash occurs, or if fever worsens or persists >3 days during therapy, consult healthcare provider. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or lasts >2 days, discontinue use and consult healthcare provider.
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Chlorpheniramine: Substrate of CYP2D6 (minor), 3A4 (major); Inhibits CYP2D6 (weak)
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
INTERNATIONAL BRAND NAMES — Coldrex Night (NZ); Panadol Allergy Sinus (AU); Sinumax Allergy Sinus (ZA)
PHARMACODYNAMICS / KINETICS — See individual agents.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
SPECIAL ALERTS
Health Canada: Labeling Changes for OTC Cough and Cold Preparations - December, 2008
Health Canada has issued an advisory to Canadian consumers regarding upcoming labeling changes for the use of over-the-counter (OTC) cough and cold medicines in children. Specific labeling changes as well as other important information may be found at http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2008/2008_184-eng.php.
Manufacturers Voluntarily Change Pediatric OTC Product Labeling - October 7, 2008
Leading manufacturers of over-the-counter (OTC) pediatric cough and cold products, in consultation with the Food and Drug Administration (FDA), have announced that they are voluntarily transitioning product labeling as it relates to children <4 years of age. The decision to change the labeling followed a meeting on October 2, 2008, conducted by the FDA to gather additional information related to the use of these products in children. The safety of the ingredients in these products was not in question. It was found that dosing errors and accidental ingestions were the leading cause of rare adverse events in children. The new product labeling will state "Do not use in children under four years of age." In addition, products with certain antihistamines will warn parents not to use these products to sedate or make a child sleepy. Labeling of adult products will not change. New product labels will be introduced during the 2008-2009 cough and cold season and some products will have the updated labeling by mid-October. Products with the old labeling will not be removed from the market. Prescription products are not affected.
It is important to note that these medications have not been shown to be unsafe when used correctly. Pharmacists may continue to see health care practitioners recommending these agents for use in pediatric patients, and should help to ensure that they are being used safely and at appropriate dosages. Parents should be advised that OTC cough and cold products are safe and effective when used as directed, but that they should not be used in children <4 years of age unless instructed to do so by their healthcare provider. Counseling tips from the Consumer Healthcare Products Association (CHPA) also include: Always follow dosing instructions exactly and use measuring devices provided with the medicine. Never give 2 medicines at the same time that contain the same active ingredient. Do not give a medicine intended for use in adults to a child.
Additional tips and information related to the labeling changes can be found on the following educational website of the CHPA: http://www.otcsafety.org.
The FDA had previously issued a Public Health Advisory reminding patients and caregivers that OTC cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report which noted that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), and cough suppressants (eg, dextromethorphan). In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group.
For additional information, refer to the following websites:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094913.htm
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116839.htm
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, "Infant Deaths Associated with Cough and Cold Medications - Two States, 2005,"MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
U.S. BRAND NAMES — Drinex [OTC]; Relief-SF®
PHARMACOLOGIC CATEGORY
Alpha/Beta Agonist
Analgesic, Miscellaneous
Histamine H1 Antagonist
Histamine H1 Antagonist, First Generation
DOSING: ADULTS — Relief of cold, allergy, and sinus symptoms: Oral: Product labeling:
Drinex: 1 tablet 3-4 times/day (maximum: 4 tablets/24 hours); do not take for >7 days
Relief-SF®: 1-2 caplets every 6 hours (maximum: 8 caplets/24 hours)
DOSING: PEDIATRIC
Relief of cold, allergy, and sinus symptoms: Oral: Children ≥ 12 years of age: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis; however, cases of hepatotoxicity at daily acetaminophen dosages <4 g/day have been reported. Avoid chronic use in hepatic impairment.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet: Acetaminophen 325 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Relief-SF®: Acetaminophen 500 mg, chlorpheniramine maleate 2 mg, and pseudoephedrine hydrochloride 30 mg
Tablet:
Drinex: Acetaminophen 650 mg, chlorpheniramine maleate 4 mg, and pseudoephedrine hydrochloride 60 mg
DOSAGE FORMS: CONCISE
Caplet: Acetaminophen 325 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Relief-SF®: Acetaminophen 500 mg, chlorpheniramine 2 mg, and pseudoephedrine 30 mg
Tablet:
Drinex [OTC]: Acetaminophen 650 mg, chlorpheniramine 4 mg, and pseudoephedrine 60 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Temporary relief of cold, allergy, or sinus symptoms
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Use of MAO inhibitors within 14 days; concurrent use with other products containing acetaminophen
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression which may impair physical or mental abilities; patients must be cautioned about performing tasks which require metal alertness (eg, operating machinery or driving).
Disease-related concerns: Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. Hepatic impairment: Use caution in patients with hepatic impairment; acetaminophen may cause severe hepatic toxicity with acute overdose.
Concurrent drug therapy issues: Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations: Elderly: Use with caution in the elderly; more likely to experience adverse reactions to sympathomimetics. Pediatrics: Use with caution in children; may cause excitability. Do not exceed pediatric dosing recommendations. If no recommendations for patient's age exist on OTC labeling, the product should not be administered without the guidance of a physician.
Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>7 days in adults (>5 days in children) during use, consult a physician. If redness, swelling, or rash occurs, or if fever worsens or persists >3 days during therapy, consult healthcare provider. If sore throat is severe, accompanied by fever, nausea/vomiting, headache, swelling or rash, or lasts >2 days, discontinue use and consult healthcare provider.
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Chlorpheniramine: Substrate of CYP2D6 (minor), 3A4 (major); Inhibits CYP2D6 (weak)
DRUG INTERACTIONS
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced hepatotoxicity. Avoid ethanol or limit to <3 drinks/day.
INTERNATIONAL BRAND NAMES — Coldrex Night (NZ); Panadol Allergy Sinus (AU); Sinumax Allergy Sinus (ZA)
PHARMACODYNAMICS / KINETICS — See individual agents.
Acetaminophen, caffeine, and dihydrocodeineAcetaminophen, caffeine, and dihydrocodeine
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Panlor® DC may be confused with Pamelor®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
U.S. BRAND NAMES — Panlor® DC; Panlor® SS; Trezix®; ZerLor™
PHARMACOLOGIC CATEGORY
Analgesic Combination (Opioid)
DOSING: ADULTS — Relief of pain: Oral:
Panlor® DC, Trezix®: 2 capsules every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 10 capsules/24 hours)
Panlor® SS, ZerLor™ : 1 tablet every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 5 tablets/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Panlor® DC: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Trezix®: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Tablet:
Panlor® SS, ZerLor™ : Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine bitartrate 32 mg
DOSAGE FORMS: CONCISE
Capsule:
Panlor® DC, Trezix®: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine 16 mg
Tablet:
Panlor® SS, ZerLor™ : Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine 32 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Tablet
USE — Relief of moderate to moderately-severe pain
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined. Most common reactions with this combination include:
Central nervous system: Dizziness, drowsiness, lightheadedness, sedation
Dermatologic: Pruritus, skin reactions
Gastrointestinal: Constipation, nausea, vomiting
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, caffeine, dihydrocodeine, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Hypotension: Use with caution in patients with hypotension. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with severe renal impairment. Respiratory disease: Use with caution in patients with respiratory diseases including asthma, emphysema, and/or COPD. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: MAO inhibitors: Use with caution with concurrent use of MAO inhibitors.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Caffeine: May cause CNS and cardiovascular stimulation, as well as GI irritation in high doses. Use with caution in patients with a history of peptic ulcer or GERD; avoid in patients with symptomatic cardiac arrhythmias. Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — C-III
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Caffeine: Substrate of CYP1A2 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 3A4 (moderate)
Dihydrocodeine: Substrate of CYP2D6 (minor)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
QuiNIDine: May diminish the analgesic effect of Dihydrocodeine. Risk D: Consider therapy modification
Quinolone Antibiotics: May decrease the metabolism of Caffeine. Exceptions: Gatifloxacin; Gemifloxacin; Levofloxacin; Lomefloxacin; Moxifloxacin; Nalidixic Acid; Ofloxacin; Sparfloxacin; Trovafloxacin. Risk C: Monitor therapy
Regadenoson: Caffeine may diminish the vasodilatory effect of Regadenoson. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced toxicity. Ethanol may also increase CNS depression.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reproduction studies have not been conducted with this combination.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acetaminophen and caffeine are both excreted in breast milk. Specific information for dihydrocodeine is not available; however, similar agents (eg, codeine, morphine) are excreted in breast milk.
PRICING — (data from drugstore.com)
Capsules (Panlor DC)
356.4-30-16 mg (30): $46.99
Tablets (Panlor SS)
712.8-60-32 mg (30): $58.99
MECHANISM OF ACTION
Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.
Caffeine is a CNS stimulant; use with acetaminophen and dihydrocodeine increases the level of analgesia provided by each agent.
Dihydrocodeine binds to opiate receptors
Sound-alike/look-alike issues:
Panlor® DC may be confused with Pamelor®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.
U.S. BRAND NAMES — Panlor® DC; Panlor® SS; Trezix®; ZerLor™
PHARMACOLOGIC CATEGORY
Analgesic Combination (Opioid)
DOSING: ADULTS — Relief of pain: Oral:
Panlor® DC, Trezix®: 2 capsules every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 10 capsules/24 hours)
Panlor® SS, ZerLor™ : 1 tablet every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 5 tablets/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule:
Panlor® DC: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Trezix®: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Tablet:
Panlor® SS, ZerLor™ : Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine bitartrate 32 mg
DOSAGE FORMS: CONCISE
Capsule:
Panlor® DC, Trezix®: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine 16 mg
Tablet:
Panlor® SS, ZerLor™ : Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine 32 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Tablet
USE — Relief of moderate to moderately-severe pain
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined. Most common reactions with this combination include:
Central nervous system: Dizziness, drowsiness, lightheadedness, sedation
Dermatologic: Pruritus, skin reactions
Gastrointestinal: Constipation, nausea, vomiting
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, caffeine, dihydrocodeine, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming ≥ 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Hypotension: Use with caution in patients with hypotension. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with severe renal impairment. Respiratory disease: Use with caution in patients with respiratory diseases including asthma, emphysema, and/or COPD. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: MAO inhibitors: Use with caution with concurrent use of MAO inhibitors.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Caffeine: May cause CNS and cardiovascular stimulation, as well as GI irritation in high doses. Use with caution in patients with a history of peptic ulcer or GERD; avoid in patients with symptomatic cardiac arrhythmias. Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — C-III
METABOLISM / TRANSPORT EFFECTS
Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Caffeine: Substrate of CYP1A2 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 3A4 (moderate)
Dihydrocodeine: Substrate of CYP2D6 (minor)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Anticonvulsants (Hydantoin): May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Cholestyramine Resin: May decrease the absorption of Acetaminophen. Effect is minimal if cholestyramine is administered 1 hour after acetaminophen. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Imatinib: May increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Isoniazid: May enhance the adverse/toxic effect of Acetaminophen. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
QuiNIDine: May diminish the analgesic effect of Dihydrocodeine. Risk D: Consider therapy modification
Quinolone Antibiotics: May decrease the metabolism of Caffeine. Exceptions: Gatifloxacin; Gemifloxacin; Levofloxacin; Lomefloxacin; Moxifloxacin; Nalidixic Acid; Ofloxacin; Sparfloxacin; Trovafloxacin. Risk C: Monitor therapy
Regadenoson: Caffeine may diminish the vasodilatory effect of Regadenoson. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic effect of Thiazide Diuretics. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Acetaminophen may enhance the anticoagulant effect of Vitamin K Antagonists. Most likely with daily acetaminophen doses >1.3 g for >1 week. Risk C: Monitor therapy
ETHANOL / NUTRITION / HERB INTERACTIONS
Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced toxicity. Ethanol may also increase CNS depression.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reproduction studies have not been conducted with this combination.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acetaminophen and caffeine are both excreted in breast milk. Specific information for dihydrocodeine is not available; however, similar agents (eg, codeine, morphine) are excreted in breast milk.
PRICING — (data from drugstore.com)
Capsules (Panlor DC)
356.4-30-16 mg (30): $46.99
Tablets (Panlor SS)
712.8-60-32 mg (30): $58.99
MECHANISM OF ACTION
Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.
Caffeine is a CNS stimulant; use with acetaminophen and dihydrocodeine increases the level of analgesia provided by each agent.
Dihydrocodeine binds to opiate receptors
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