Acetaminophen, dextromethorphan, and pseudoephedrine

SPECIAL ALERTS Infant Deaths Associated with Cough and Cold Medications - January 2007
The Centers for Disease Control and Prevention (CDC) has released a report concerning the use of cough and cold medications in children <2 years of age. Products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), cough suppressants (eg, dextromethorphan), and expectorants are often used in this age group. The CDC notes that during 2004 and 2005, ~ 1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with these medications.
During this time period, 3 infants <6 months of age died. All 3 had postmortem blood levels of pseudoephedrine, ranging from 4743-7100 ng/mL (therapeutic levels for children 2-12 years: 180-500 ng/mL). In addition, 2 of the 3 infants also had detectable levels of dextromethorphan. Although dextromethorphan has been shown to be effective to reduce cough in adults, the same efficacy has not been documented in young children. The American Academy of Pediatrics and the American College of Chest Physicians do not recommend the use of dextromethorphan for over-the-counter (OTC) use in young children.
Safety and efficacy for the use of cough and cold products in children <2 years of age is limited. The Food and Drug Administration (FDA) notes that there are no approved OTC uses for these products in children <2 years of age. Clinicians are reminded to ask caregivers about the use of OTC products in order to avoid exposure to multiple medications containing the same ingredient. Caregivers are reminded that OTC cough and cold products should not be used in children <2 years of age except under specific direction by their healthcare provider.
For additional information, refer to the following CDC website: 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 — Comtrex® Non-Drowsy Cold and Cough Relief [OTC] [DSC]; Infants' Tylenol® Cold Plus Cough Concentrated Drops [OTC] [DSC]; Sudafed® Severe Cold [OTC]; Triaminic® Cough and Sore Throat Formula [OTC] [DSC]; Tylenol® Cold Day Non-Drowsy [OTC]; Tylenol® Flu Non-Drowsy Maximum Strength [OTC]; Vicks® DayQuil® Multi-Symptom Cold and Flu [OTC] [DSC]
PHARMACOLOGIC CATEGORY AntihistamineAntitussive
DOSING: ADULTS Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-7 hours as needed; do not exceed 4 g/day
Cough suppressant (Antitussive): Oral: Based on dextromethorphan component: 10-20 mg every 4-8 hours or 30 mg every 8 hours; do not exceed 120 mg/24 hours
Nasal congestion (Decongestant): Oral: Based on pseudoephedrine component: 60 mg every 4 hours (maximum: 360 mg/24 hours)
Product labeling:
Sudafed® Severe Cold, Tylenol® Flu Non-Drowsy Maximum Strength: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours)
Tylenol® Cold Non-Drowsy: Oral: 2 doses every 6 hours (maximum: 8 doses/24 hours)
DOSING: PEDIATRIC Analgesic: Oral: Based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours as needed; do not exceed 5 doses/24 hours.
Cough suppressant: Oral: Based on dextromethorphan component: Children 6-12 years: 15 mg every 6-8 hours; do not exceed 60 mg/24 hours Children >12 years: Refer to adult dosing.
Decongestant: Oral: Based on pseudoephedrine component: Children: 2-6 years: 15 mg every 4 hours (maximum: 90 mg/24 hours) 6-12 years: 30 mg every 4 hours (maximum: 180 mg/24 hours) Children >12 years: Refer to adult dosing.
Product labeling:
Infants' Tylenol® Cold Plus Cough Concentrated Drops: Oral: Children 2-3 years (24-55 lb): 2 dropperfuls every 4-6 hours (maximum: 4 doses/24 hours)
Sudafed® Severe Cold, Thera-Flu® Non-Drowsy Maximum Strength (gelcap), Tylenol® Flu Non-Drowsy Maximum Strength: Oral: Children >12 years: Refer to adult dosing.
Tylenol® Cold Non-Drowsy: Oral: Children 6-11 years: 1 dose every 6 hours (maximum: 4 doses/24 hours) Children 12 years: Refer to adult dosing.
Thera-Flu® Non-Drowsy Maximum Strength: Oral: Children >12 years: 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. [DSC] = Discontinued product
Caplet: Comtrex® Non-Drowsy Cold and Cough Relief: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg [contains benzoic acid] [DSC] Tylenol® Cold Day Non-Drowsy: Acetaminophen 325 mg dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg
Capsule, liquid: Vicks® DayQuil® Multi-Symptom Cold and Flu: Acetaminophen 250 mg, dextromethorphan hydrobromide 10 mg, and pseudoephedrine hydrochloride 30 mg [DSC]
Gelcap: Tylenol® Cold Day Non-Drowsy: Acetaminophen 325 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg [contains benzyl alcohol] [DSC] Tylenol® Flu Non-Drowsy Maximum Strength: Acetaminophen 500 mg, dextromethorphan hydrobromide 15 mg, and pseudoephedrine hydrochloride 30 mg
Liquid: Triaminic® Cough and Sore Throat Formula: Acetaminophen 160 mg, dextromethorphan hydrobromide 7.5 mg, and pseudoephedrine hydrochloride 15 mg per 5 mL (120 mL, 240 mL) [contains benzoic acid; grape flavor] [DSC] Vicks® DayQuil® Multi-Symptom Cold and Flu: Acetaminophen 325 mg, dextromethorphan hydrobromide 10 mg, and pseudoephedrine hydrochloride 30 mg per 15 mL (175 mL) [DSC]
Suspension, oral [drops]: Infants' Tylenol® Cold Plus Cough Concentrated Drops: Acetaminophen 160 mg, dextromethorphan hydrobromide 5 mg, and pseudoephedrine hydrochloride 15 mg per 1.6 mL (15 mL) [1.6 mL = 2 dropperfuls] [cherry flavor] [DSC]
DOSAGE FORMS: CONCISE Caplet: Sudafed® Severe Cold [OTC], Tylenol® Cold Day Non-Drowsy [OTC]: Acetaminophen 325 mg, dextromethorphan 15 mg, and pseudoephedrine 30 mg
Gelcap: Tylenol® Flu Non-Drowsy Maximum Strength [OTC]: Acetaminophen 500 mg, dextromethorphan 15 mg, and pseudoephedrine 30 mg
GENERIC EQUIVALENT AVAILABLE — No
USE — Treatment of mild-to-moderate pain and fever; symptomatic relief of cough and congestion
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, dextromethorphan, pseudoephedrine, or any component of the formulation
DRUG INTERACTIONS 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)
Also see individual agents.
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.
CANADIAN BRAND NAMES — Contac® Complete; Contac® Cough, Cold and Flu Day & Night™; Sudafed® Cold & Cough Extra Strength; Tylenol® Cold Daytime
INTERNATIONAL BRAND NAMES — Contac Complete (CA); Contac Cough, Cold and Flu Day & Night® (CA); Sudafed Cold & Cough Extra Strength (CA); Tylenol Cold Daytime (CA)
PHARMACODYNAMICS / KINETICS — See individual agents.