Acetaminophen, chlorpheniramine, phenylephrine, and phenyltoloxamine

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

Brand Names: U.S. norel® SR
Pharmacologic Category Alkylamine Derivative; Alpha-Adrenergic Agonist; Analgesic, Miscellaneous; Decongestant; Ethanolamine Derivative; Histamine H1; Agonist Histamine H1 Antagonist, First Generation
Dosing: Adult Relief of cold, allergy, or sinus symptoms: Oral: One tablet every 12 hours
Dosing: Pediatric Children >12 years: Refer to adult dosing.
Dosing: Geriatric Refer to adult dosing.
Dosing: Renal Impairment No dosage adjustment recommended.
Dosing: Hepatic Impairment No dosage adjustment recommended.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, extended release, oral:

norel® SR: Acetaminophen 325 mg, chlorpheniramine maleate 8 mg, phenylephrine hydrochloride 40 mg, and phenyltoloxamine citrate 50 mg [scored]

Administration Tablets may be split; do not crush or chew.
Use Temporary relief of cold, allergy, or sinus symptoms caused from inhalation of airborne irritants
Adverse Reactions Significant Frequency not defined.
Cardiovascular: Chest tightness

Central nervous system: Fever, fatigue, psychotic episodes

Dermatologic: Bruising

Hematologic: Anemia, bleeding

Neuromuscular & skeletal: Weakness

Miscellaneous: Allergic reactions

Contraindications Hypersensitivity to acetaminophen, chlorpheniramine, phenylephrine, phenyltoloxamine, or any component of the formulation; severe hypertension; narrow-angle glaucoma; acute asthma
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:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease); contraindicated with severe hypertension.

• Diabetes: Use with caution in patients with diabetes mellitus.

• Hepatic impairment: Use with caution in patients with hepatic impairment or active liver disease, including viral hepatitis.

• Increased intraocular pressure: Use with caution in patients with increased intraocular pressure.

• Psychiatric: Use with caution in patients with psychosis or other psychiatric disorders.

• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

• Renal impairment: Use with caution in patients with severe renal impairment.

• Respiratory disease: Use with caution in patients with asthma or other chronic breathing disorders.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Acetaminophen: Avoid or limit use of other acetaminophen-containing products; limit total acetaminophen dose to <4 g/day.

• 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: Antihistamines may cause excitation in young children.

Other warnings/precautions:

• Appropriate use: Continued or worsening of symptoms could be a sign of a more serious medical problem and should be further evaluated by a healthcare provider.

Drug Interactions
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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: Levocabastine (Nasal); 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

Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification

Benzylpenicilloyl Polylysine: Alpha1-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient’s ability to mount a wheal and flare response. Risk D: Consider therapy modification

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. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). 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

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

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

FentaNYL: Alpha1-Agonists may decrease the serum concentration of FentaNYL. Specifically, fentanyl nasal spray serum concentrations may decrease and onset of effect may be delayed. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Imatinib: Acetaminophen may enhance the hepatotoxic effect of Imatinib. 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

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

Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification

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

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

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

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. 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: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Pregnancy Risk Factor C (show table)
Pregnancy Implications Animal reproduction studies have not been conducted with this combination. Refer to individual agents.
Lactation Not recommended
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