Dosing and uses of Diclegis (doxylamine/pyridoxine)
Adult dosage forms and strengths
doxylamine/pyridoxine
tablet, delayed-release
- 10mg/10mg
Nausea & Vomiting of Pregnancy
Indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management
2 tablets PO on a daily basis at bedtime; if symptoms not adequately controlled, increase dose to 4 tablets each day (1 tab in AM, 1 tab mid-afternoon, and 2 tabs at bedtime)
Dosing Considerations
Not studied in women with hyperemesis gravidarum
Administration
Take on empty stomach with water; food further delays onset of action and lowers peak levels
Swallow whole, do not chew, crush, or split tablet
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Diclegis (doxylamine/pyridoxine) adverse (side) effects
>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
Warnings
Contraindications
Hypersensitivity
MAO inhibitors intensify and prolong doxylamine’s adverse effects (ie, anticholinergic, CNS)
Cautions
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
Pregnancy and lactation
Pregnancy category: A
Lactation: Do not breast feed; doxylamine molecular weight is low enough to distribute into human breast milk
Excitement, irritability, and sedation reported in nursing infants presumably exposed to doxylamine through breast milk; infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects resulting in worsening of apnea or respiratory conditions
Pyridoxine is excreted in breast milk; there have been no reports of adverse effects in infants
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.
Pharmacology of Diclegis (doxylamine/pyridoxine)
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
