Doxylamine and Pyridoxine

Pronunciation

(dox IL a meen & peer i DOX een)

Synonyms

Doxylamine Succinate and Pyridoxine Hydrochloride; Pyridoxine and Doxylamine

Canadian Brand Names

Diclectin®

Use

Treatment of pregnancy-associated nausea and vomiting

Restrictions

Not available in U.S.

Pregnancy Risk Factor

A

Pregnancy Implications

Doxylamine has been approved for use in pregnancy-associated nausea and vomiting.

Lactation

Excretion in breast milk unknown

Contraindications

Hypersensitivity to doxylamine, pyridoxine, or any component of the formulation

Warnings/Precautions

May cause drowsiness; patient should avoid tasks requiring alertness (eg, driving, operating machinery) until effects are known. Sedative effects of CNS depressants or ethanol are potentiated. Use with caution in patients with angle-closure glaucoma, pyloroduodenal obstruction (including stenotic peptic ulcer), urinary tract obstruction (including bladder neck obstruction and symptomatic prostatic hyperplasia), hyperthyroidism, increased intraocular pressure, and cardiovascular disease (including hypertension and tachycardia).

Adverse Reactions

Frequency not defined.

Cardiovascular: Palpitations, tachycardia

Central nervous system: Dizziness, disorientation, drowsiness, headache, paradoxical CNS stimulation, vertigo

Gastrointestinal: Anorexia, dry mucous membranes, diarrhea, constipation, epigastric pain, xerostomia

Genitourinary: Dysuria, urinary retention

Ocular: Blurred vision, diplopia

Drug Interactions

Anticholinergic agents: Central and/or peripheral anticholinergic syndrome can occur when administered with narcotic analgesics, phenothiazines and other antipsychotics (especially with high anticholinergic activity), tricyclic antidepressants, quinidine and some other antiarrhythmics, and antihistamines.

Cholinergic agents: Drugs with high anticholinergic activity may antagonize the therapeutic effect of cholinergic agents; includes donepezil, rivastigmine, and tacrine.

CNS depressants: Sedative effects may be additive with CNS depressants; includes ethanol, benzodiazepines, barbiturates, narcotic analgesics, and other sedative agents; monitor for increased effect.

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).

Mechanism of Action

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. Pyridoxine is a vitamin which may have modest antiemetic effects.

Pharmacodynamics/Kinetics

Absorption: Well absorbed

Distribution: Vd: 2.5 L/kg

Metabolism: Via multiple metabolic pathways including N-demethylation, oxidation, hydroxylation, N-acetylation to metabolites including nordoxylamine, dinordoxylamine

Half-life elimination: 10-12 hours

Excretion: Urine (primarily as metabolites)

Dosage

Oral: Adults: Two delayed release tablets (a total of doxylamine 20 mg and pyridoxine 20 mg) at bedtime; in severe cases or in cases with nausea/vomiting during the day, dosage may be increased by 1 tablet in the morning and/or afternoon

Dosage adjustment in renal impairment: No dosage adjustment required

Administration

Main dose should be taken at bedtime to provide relief in the early morning hours.

Patient Education

Inform prescriber of all other prescriptions, OTC medications, or herbal products you are taking and any allergies you have. Take exactly as directed; do not take more than recommended. May cause drowsiness, headache, disorientation, or double vision (use caution when driving or engaged is tasks requiring alertness until response to drug is known); mouth sores, gastrointestinal upset, lack of appetite (small frequent meals, frequent mouth care, or sucking lozenges may help). Report rapid heart beat, palpitations; change in urinary pattern (urinary retention); unusual CNS changes; or other persistent adverse reactions.

Dosage Forms

Tablet, delayed release: Doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg

International Brand Names

Diclectin® (CA)

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