Acetaminophen and phenyltoloxamine

Acetaminophen and phenyltoloxamine: Drug information
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(For additional information see “Acetaminophen and phenyltoloxamine: Patient drug information”)

Brand Names: U.S. Aceta-Gesic [OTC]; BP Poly 650 [DSC]; Lagesic™ [DSC]; Phenagesic [OTC] [DSC]; RhinoFlex™; RhinoFlex™-650; Zgesic
Pharmacologic Category Analgesic, Miscellaneous
Dosing: Adult
Pain (Analgesic): Oral: Based on acetaminophen component: 325-650 mg every 4-6 hours as needed (maximum: 4 g/day)

Product-specific labeling: Oral:

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)

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:

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.

Zgesic: Children >12 years: Refer to adult dosing.

Dosing: Geriatric 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: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet, extended release [scored]:

Lagesic™: Acetaminophen 600 mg and phenyltoloxamine citrate 66 mg [DSC]

Tablet: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg

Aceta-Gesic, Phenagesic [DSC]: Acetaminophen 325 mg and phenyltoloxamine citrate 30 mg

BP Poly 650 [DSC]: Acetaminophen 650 mg and phenyltoloxamine citrate 60 mg

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

Generic Equivalent Available: U.S. 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
Medication Safety Issues
Sound-alike/look-alike issues:
Percogesic® may be confused with paregoric, Percodan®

Other safety concerns:
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.

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 g/day.

• Self-medication (OTC use): When used for self-medication, patients should be instructed to contact healthcare provider if used for fever lasting >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
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
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

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy

Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Risk C: Monitor therapy

Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Imatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. 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

Metyrapone: May increase the serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Risk D: Consider therapy modification

SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the serum concentration of Acetaminophen. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 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.
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.

 

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