Acetaminophen, dextromethorphan, and doxylamine

Acetaminophen, dextromethorphan, and doxylamine: Drug information
Copyright 1978-2011 Lexicomp, Inc. All rights reserved.
(For additional information see “Acetaminophen, dextromethorphan, and doxylamine: Patient drug information”)

Brand Names: U.S. All-Nite [OTC]; Tylenol® Cough & Sore Throat Nighttime [OTC]; Vicks® NyQuil® Cold & Flu Multi-Symptom [OTC]
Pharmacologic Category Analgesic, Miscellaneous; Antitussive; Ethanolamine Derivative; Histamine H1; Antagonist Histamine H1 Antagonist, First Generation
Dosing: Adult Relief of cold and flu symptoms: Oral: Two capsules 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: Geriatric Refer to adult dosing.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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]

Generic Equivalent Available: U.S. 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)
Medication Safety Issues
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 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 g/day (adults) or <2.6 g/day (children <12 years of age).

• Self-medication (OTC use): Patients with glaucoma 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 or cough increases in severity or persists >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
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

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

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

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

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

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

Darunavir: May increase the serum concentration of CYP2D6 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

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

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

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

QuiNIDine: May increase the serum concentration of Dextromethorphan. Management: Avoid concurrent use of these agents when possible, unless the increased psychoactive effects of dextromethorphan are desired. Since codeine activation is also inhibited by quinidine, codeine is unlikely to be suitable as an alternative antitussive. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. 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

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.
Dietary Considerations Some products may contain sodium.

REFERENCES
Antlitz AM, Mead JA Jr, and Tolentino MA, “Potentiation of Oral Anticoagulant Therapy by Acetaminophen,” Curr Ther Res Clin Exp, 1968, 10(10):501-7. [PubMed 4971464]
Bagheri H, Bernhard NB, and Montastruc JL, “Potentiation of the Acenocoumarol Anticoagulant Effect by Acetaminophen,” Ann Pharmacother, 1999, 33(4):506. [PubMed 10332548]
Bartle WR and Blakely JA, “Potentiation of Warfarin Anticoagulation by Acetaminophen,” JAMA, 1991, 265(10):1260. [PubMed 1995971]
Boeijinga JJ, Boerstra EE, Ris P, et al, “Interaction Between Paracetamol and Coumarin Anticoagulants,” Lancet, 1982, 1(8270):506. [PubMed 6121161]
Gadisseur AP, Van Der Meer FJ, and Rosendaal FR, “Sustained Intake of Paracetamol (Acetaminophen) During Oral Anticoagulant Therapy With Coumarins Does Not Cause Clinically Important INR Changes: A Randomized Double-Blind Clinical Trial,” J Thromb Haemost, 2003, 1(4):714-7. [PubMed 12871405]
Gebauer MG, Nyfort-Hansen K, Henschke PJ, et al, “Warfarin and Acetaminophen Interaction,” Pharmacotherapy, 2003, 23(1):109-12. [PubMed 12523469]
Hylek EM, Heiman H, Skates SJ, et al, “Acetaminophen and Other Risk Factors for Excessive Warfarin Anticoagulation,” JAMA, 1998, 279(9):657-62. [PubMed 9496982]
Kwan D, Bartle WR, and Walker SE, “The Effects of Acute and Chronic Acetaminophen Dosing on the Pharmacodynamics and Pharmacokinetics of (R)- and (S)-Warfarin,” Clin Pharmacol Ther, 1995, 57:212.
Rubin RN, Mentzer RL, and Budzynski AZ, “Potentiation of Anticoagulant Effect of Warfarin by Acetaminophen (Tylenol®),” Clin Res, 1984, 32:698a.
van den Bemt PM, Geven LM, Kuitert NA, et al, “The Potential Interaction Between Oral Anticoagulants and Acetaminophen in Everyday Practice,” Pharm World Sci, 2002, 24(5):201-4. [PubMed 12426965]