Acetaminophen and pseudoephedrine

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

Brand Names: U.S. Ornex® Maximum Strength [OTC]; Ornex® [OTC]
Brand Names: Canada Contac® Cold and Sore Throat, Non Drowsy, Extra Strength; Dristan® N.D.; Dristan® N.D., Extra Strength; Sinutab® Non Drowsy; Sudafed® Head Cold and Sinus Extra Strength; Tylenol® Decongestant; Tylenol® Sinus
Pharmacologic Category Alpha/Beta Agonist; Analgesic, Miscellaneous
Dosing: Adult Relief of cold, flu or sinusitis symptoms: Oral (Ornex®, Ornex® Maximum Strength): Two caplets every 4-6 hours as needed (maximum: 8 caplets/day)
Dosing: Pediatric
Relief of cold, flu or sinusitis symptoms: Oral:

Children 6-11 years (Ornex®): One caplet every 4-6 hours as needed (maximum: 4 caplets/day)

Children ≥12 years: Refer to adult dosing.

Dosing: Geriatric 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: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet:

Ornex®: Acetaminophen 325 mg and pseudoephedrine hydrochloride 30 mg

Ornex® Maximum Strength: Acetaminophen 500 mg and pseudoephedrine hydrochloride 30 mg

Generic Equivalent Available: U.S. Yes
Use Temporary relief of nasal congestion, and minor aches and pains associated with colds, flu, sinusitis, or allergies
Medication Safety Issues
Sound-alike/look-alike issues:
Ornex® may be confused with Orexin®, Orinase®

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 MAO inhibitor therapy or within 14 days of therapy; concurrent use with other products containing acetaminophen
Warnings/Precautions
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.

Special populations:

• Pediatrics: 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.

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 hypertension, thyroid disease, diabetes mellitus, cardiovascular disease, or prostatic hyperplasia should consult a physician prior to use. Products containing acetaminophen are not recommended in patients consuming ≥3 alcoholic beverages/day; consult a physician. If symptoms persists >7 days or are accompanied by fever that lasts for >3 days, consult a physician. Discontinue and contact healthcare provider if nervousness, dizziness, or sleeplessness occur.

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 )
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. 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: Alpha-/Beta-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

Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. 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

Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. 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

FentaNYL: Alpha-/Beta-Agonists (Indirect-Acting) 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

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 Alpha-/Beta-Agonists (Indirect-Acting). 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

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

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. 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

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy

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

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.
International Brand Names Day Flu (EC); Panadol Cold (MY); Panadol Sinus (AU, HK); Sinumax Ped (ZA); Sinutab (BE)
Pharmacodynamics/Kinetics See individual agents.

 

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]