doxylamine/pyridoxine (Rx)

>10%

Somnolence (14.3%)

Postmarketing Reports

Cardiac disorders: Dyspnea, palpitation, tachycardia

Ear and labyrinth disorders: Vertigo

Eye disorders: Vision blurred, visual disturbances

Gastrointestinal disorders: Abdominal distension, abdominal pain, constipation, diarrhea

General disorders and administration site conditions: Chest discomfort, fatigue, irritability, malaise

Immune system disorders: Hypersensitivity

Nervous system disorders: Dizziness, headache, migraines, paresthesia, psychomotor hyperactivity

Psychiatric disorders: Anxiety, disorientation, insomnia, nightmares

Renal and urinary disorders: Dysuria, urinary retention

Skin and subcutaneous tissue disorders: Hyperhidrosis, pruritus, rash, rash maculopapular

Contraindications

Hypersensitivity to drug or excipients

Concomitant use with MAO inhibitors

Cautions

Not evaluated for use in hyperemesis gravidarum

Coadministration with alcohol and other CNS depressants may cause additive sedation and is not recommended; combination may cause severe drowsiness leading to falls or accidents

Somnolence due to anticholinergic effects is common; avoid activities requiring mental alertness

Anticholinergic effects may exacerbate conditions such as asthma, increased intraocular pressure, narrow angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, and urinary bladder-neck obstruction

Drug interaction overview

• False positive drug screens for methadone, opiates, and PCP can occur with doxylamine succinate/pyridoxine hydrochloride use; confirmatory tests, such as Gas Chromatography Mass Spectrometry (GC-MS), should be used to confirm identity of substance in the event of positive immunoassay result

Pregnancy

Intended for treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management; maternal risks are discussed throughout the labeling; no increased risk for congenital malformations reported in epidemiologic studies in pregnant women

Lactation

Women should not breastfeed while on therapy; molecular weight of doxylamine succinate is low enough that passage into breast milk can be expected; excitement, irritability and sedation reported in nursing infants presumably exposed to doxylamine succinate through breast milk; infants with apnea or other respiratory syndromes may be particularly vulnerable to sedative effects of drug resulting in worsening of their apnea or respiratory conditions

Pyridoxine hydrochloride is excreted into breast milk; adverse events in infants presumably exposed to pyridoxine hydrochloride through breast milk reported

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Mechanism of action for efficacy for morning sickness is unknown

Doxylamine: Ethanolamine derivative antihistamine

Pyridoxine: Vitamin B6 analog

Absorption

Peak plasma time: 7.8 hr (doxylamine); 5.6 hr (pyridoxine)

Peak plasma concentration: 168.6 ng/mL (doxylamine); 46.1 ng/mL (pyridoxine)

AUC: 3721 ng•hr/mL (doxylamine); 64.5 ng•hr/mL (pyridoxine)

Distribution

Protein bound: Pyridoxine is highly protein bound (primarily to albumin); main active metabolite (PLP) accounts for at least 60% of circulating vitamin B6 concentrations

Metabolism

Doxylamine is biotransformed in the liver by N-dealkylation to its principle metabolites N-desmethyldoxylamine and N, N-didesmethyldoxylamine

Pyridoxine is a prodrug primarily metabolized in the liver to pyridoxal 5’-phosphate (PLP), pyridoxal, pyridoxamine, and pyridoxamine 5’-phosphate

Elimination

Half-life: 12.5 hr (doxylamine); 0.5 hr (pyridoxine)

Excretion: Principle metabolites of doxylamine excreted in urine

Oral Administration

Take on empty stomach with water; food further delays onset of action and lowers peak levels

Swallow tablet whole, do not chew, crush, or split