Drug Information

Acetaminophen, codeine, and doxylamine

Acetaminophen, codeine, and doxylamine: Drug information
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(For additional information see “Acetaminophen, codeine, and doxylamine: Patient drug information”)
Brand Names: Canada

Mersyndol® With Codeine

Pharmacologic Category

Analgesic, Miscellaneous;
Analgesic, Opioid;
Antitussive;
Ethanolamine Derivative;
Histamine H1; Antagonist
Histamine H1 Antagonist, First Generation

Dosing: Adult

Oral: 1-2 tablets every 4 hours as needed; total dose should not exceed 12 tablets in a 24-hour period
Dosing: Pediatric

Children >12 years: Refer to adult dosing.
Dosing: Renal Impairment

No dosage adjustment required.
Dosing: Hepatic Impairment

Acetaminophen: Use with caution. Limited, low-dose therapy usually well tolerated in hepatic disease/cirrhosis. However, cases of hepatotoxicity at daily acetaminophen dosages

Codeine: Dosage adjustment of codeine is probably necessary in hepatic insufficiency; no specific guidelines available.
Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral:

Mersyndol® With Codeine: Acetaminophen 325 mg, codeine 8 mg, and doxylamine 5 mg
Product Availability

Not available in U.S.
Use

Relief of headache, cold symptoms, neuralgia, and muscular aches/pain
Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
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

Hypersensitivity to acetaminophen, codeine, doxylamine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia
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).

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

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).

Disease-related concerns:

• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison’s disease.

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension/hypotension and tachycardia).

• CNS depression/coma: Use with caution in patients with CNS depression or coma.

• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.

• 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.

• Gastrointestinal motility disorders: Use with caution in patients with gastrointestinal motility disorders; avoid in paralytic ileus.

• Glaucoma: Use with caution in patients with angle-closure glaucoma and/or increased intraocular pressure.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.

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

• Pyloroduodenal obstruction: Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer).

• Seizure disorder: Use with caution in patients with a history of seizure disorder.

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

Concurrent drug therapy issues:

• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Special populations:

• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.

• Pediatrics: Safety and efficacy have not been established in children

• Surgical patients: Use with caution in postoperative patients following thoracotomy or laparotomy due to suppression of cough.

Other warnings/precautions:

• Dosage limit: Limit total acetaminophen dose to 1.3 g for >1 week. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid ethanol (may increase CNS depression).

Herb/Nutraceutical: Avoid valerian, St John’s wort, kava kava, gotu kola (may increase CNS depression).
Pregnancy Implications

There are no adequate and well-controlled studies in pregnant women. Should not be used in pregnancy unless the potential benefit to the mother justifies possible harm to the fetus. Refer to Codeine monograph.
Lactation

No data available.
Breast-Feeding Considerations

Doxylamine may be excreted in breast milk, potentially resulting in sedative effects in nursing infants. Refer to Codeine monograph.
Monitoring Parameters

Relief of pain, respiratory and mental status, blood pressure, bowel function
International Brand Names

Mersyndol With Codeine (CA)

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. Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough supression by direct central action in the medulla; produces generalized CNS depression. Doxylamine competes with histamine for H1-receptor sites on effector cells; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity.
Pharmacodynamics/Kinetics

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See individual agents.
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REFERENCES

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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]