Acetaminophen and phenyltoloxamine

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Percogesic® may be confused with paregoric, Percodan®

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 — Aceta-Gesic [OTC]; Alpain; BeFlex; Dologesic®; Flextra-650; Flextra-DS; Genasec™ [OTC]; Hyflex-DS® [DSC]; Lagesic™ ; Percogesic® [OTC]; Phenagesic [OTC]; Phenylgesic [OTC]; RhinoFlex™ ; RhinoFlex™ -650; Staflex; Vistra 650 [DSC]; Zgesic

PHARMACOLOGIC CATEGORY
Analgesic, Miscellaneous

DOSING: ADULTS
Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-6 hours as needed (maximum: 4 g/day)

Product-specific labeling: Oral:
Dologesic®: 1-2 caplets/capsules or 15-30 mL every 4 hours (maximum: 8 caplets/24 hours or 120 mL/24 hours)
Flextra-650:1/2-1 tablet every 6 hours (maximum: 4 tablets/day)
Flextra-DS, RhinoFlex™ , RhinoFlex™ -650:1/2-1 tablet every 4 hours (maximum: 5 tablets/day)
Lagesic™ , Zgesic: 1-2 caplets/tablets every 8-12 hours (maximum: 6 tablets/24 hours)
Percogesic®: 1-2 tablets every 4 hours (maximum: 8 tablets/24 hours)

DOSING: PEDIATRIC
Analgesic: Oral:
Based on acetaminophen component: 10-15 mg/kg/dose every 4-6 hours as needed (maximum: 5 doses/24 hours)

Product-specific labeling: Oral:
Dologesic®:
Children <12 years: 1 caplet/capsule or 5 mL every 4 hours
Children ≥ 12 years: Refer to adult dosing.
Flextra-650:
Children 6 to <12 years: 1/2 tablet every 6 hours (maximum: 2 tablets/day)
Children ≥ 12 years: Refer to adult dosing.
Flextra-DS, RhinoFlex™ , RhinoFlex™ -650:
Children 6 to <12 years: 1/2 tablet every 4 hours (maximum: 2.5 tablets/day)
Children ≥ 12 years: Refer to adult dosing.
Lagesic™ :
Children 6-12 years: 1/2 to 1 caplet every 12 hours (maximum: 2 caplets/day)
Children ≥ 12 years: Refer to adult dosing.
Percogesic®: Children 6-12 years: 1 tablet every 4 hours (maximum: 4 tablets/24 hours)
Zgesic: Children >12 years: Refer to adult dosing.

DOSING: ELDERLY — Refer to adult dosing.

DOSING: RENAL IMPAIRMENT
Specific dosing adjustment not available. Monitor renal function with severe impairment.

DOSING: HEPATIC IMPAIRMENT — Use with caution. Limited, low-dose therapy is 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:
Alpain: Acetaminophen 500 mg and phenyltoloxamine citrate 60 mg
BeFlex: Acetaminophen 500 mg and phenyltoloxamine citrate 55 mg
Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg
Staflex: Acetaminophen 500 mg and phenyltoloxamine citrate 55 mg

Caplet, extended release [scored]:
Lagesic™ : Acetaminophen 600 mg and phenyltoloxamine citrate 66 mg

Capsule:
Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg

Liquid:
Dologesic®: Acetaminophen 500 mg and phenyltoloxamine citrate 30 mg per 15 mL (180 mL)

Tablet: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg
Aceta-Gesic, Genasec™ , Percogesic®, Phenagesic, Phenylgesic: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg
Flextra-650, Vistra 650 [DSC]: Acetaminophen 650 mg and phenyltoloxamine citrate 60 mg
Flextra-DS, Hyflex-DS® [DSC], RhinoFlex™ : Acetaminophen 500 mg and phenyltoloxamine citrate 50 mg
RhinoFlex™ -650: Acetaminophen 650 mg and phenyltoloxamine citrate 50 mg

Tablet, prolonged release, oral:
Zgesic: Acetaminophen 600 mg and phenyltoloxamine citrate 66 mg

DOSAGE FORMS: CONCISE
Caplet:
Alpain: Acetaminophen 500 mg and phenyltoloxamine 60 mg
BeFlex, Staflex: Acetaminophen 500 mg and phenyltoloxamine 55 mg
Dologesic®: Acetaminophen 500 mg and phenyltoloxamine 30 mg

Caplet, extended release [scored]:
Lagesic™ : Acetaminophen 600 mg and phenyltoloxamine 66 mg

Capsule:
Dologesic®: Acetaminophen 500 mg and phenyltoloxamine 30 mg

Liquid:
Dologesic®: Acetaminophen 500 mg and phenyltoloxamine 30 mg per 15 mg

Tablet: Acetaminophen 325 mg and phenyltoloxamine 30 mg
Aceta-Gesic [OTC], Genasec™ [OTC], Percogesic® [OTC], Phenagesic [OTC], Phenylgesic [OTC]: Acetaminophen 325 mg and phenyltoloxamine 30 mg
Flextra-650: Acetaminophen 650 mg and phenyltoloxamine 60 mg
Flextra-DS, RhinoFlex™ : Acetaminophen 500 mg and phenyltoloxamine 50 mg
RhinoFlex™ -650: Acetaminophen 650 mg and phenyltoloxamine 50 mg

Tablet, prolonged release, oral:
Zgesic: Acetaminophen 600 mg and phenyltoloxamine 66 mg

GENERIC EQUIVALENT AVAILABLE — Yes: Tablet

ADMINISTRATION — May be administered with food or milk.

Extended release caplet (Lagesic™ ): Caplet may be broken in half; do not chew or crush.

Prolonged release tablet (Zgesic): Swallow whole; do not chew or crush.

USE — Relief of mild-to-moderate pain

ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.

Central nervous system: Dizziness, drowsiness, lassitude

Dermatologic: Pruritus, rash

Gastrointestinal: Nausea

Ocular: Blurred vision

Miscellaneous: Diaphoresis

CONTRAINDICATIONS — Hypersensitivity to acetaminophen, phenyltoloxamine, or any component of the formulation

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: May cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients.

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. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Glaucoma: Use with caution in patients with glaucoma. Hepatic impairment: Use with caution in patients with hepatic impairment. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with renal impairment. Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.

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; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children <6 years of age.

Other warnings/precautions: Dosage limit: Limit acetaminophen dose to <4>3 days or for pain lasting >10 days in adults or >5 days in children.

METABOLISM / TRANSPORT EFFECTS — Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (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

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

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

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.

Food: Rate of absorption may be decreased when given with food.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Reproduction studies have not been conducted with this combination.

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — Acetaminophen is excreted in breast milk. Excretion of phenyltoloxamine is not known.

DIETARY CONSIDERATIONS — May be taken with food or milk.

PRICING — (data from drugstore.com)
Tablets (Flextra DS)
50-500 mg (30): $18.99

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. Phenyltoloxamine is an antihistamine (H1-blocking agent) which acts primarily to inhibit secretions in the nose, mouth, and pharynx, as well as causing CNS depression.