DICLEGIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DICLEGIS (DICLEGIS).
DICLEGIS is a fixed-dose combination of doxylamine (an antihistamine) and pyridoxine (vitamin B6). Doxylamine acts as a competitive antagonist at histamine H1 receptors, while pyridoxine is a cofactor in metabolic pathways. The exact mechanism in nausea and vomiting of pregnancy is unknown, but it is believed to involve central antihistaminergic effects and modulation of neurotransmitter synthesis.
| Metabolism | Doxylamine: metabolized primarily by CYP450 enzymes, including CYP2D6, CYP1A2, CYP2C9, and CYP2C19. Pyridoxine: metabolized to pyridoxal phosphate, mainly in the liver. |
| Excretion | Doxylamine and pyridoxine are metabolized in the liver; doxylamine is mainly excreted in urine (60%) as unchanged drug and metabolites, with lesser fecal elimination; pyridoxine is primarily renally eliminated as 4-pyridoxic acid. |
| Half-life | Doxylamine: 10-12 hours (terminal); pyridoxine: approximately 2-3 hours (clinical context: doxylamine's longer half-life supports once-daily dosing for nausea). |
| Protein binding | Doxylamine: ~50% bound (albumin); pyridoxine: ~80% bound (albumin and plasma proteins). |
| Volume of Distribution | Doxylamine: ~4.1 L/kg (extensive tissue distribution); pyridoxine: ~1.5 L/kg (distributes to liver, muscle, and tissues). |
| Bioavailability | Oral: doxylamine 70-80%; pyridoxine ~60% (due to first-pass metabolism); delayed-release formulation designed to minimize peak-trough fluctuations. |
| Onset of Action | Oral: 30-60 minutes for doxylamine, 30 minutes for pyridoxine; onset of antiemetic effect typically 1-2 hours after dosing. |
| Duration of Action | Doxylamine: 4-6 hours (sedation and antihistamine effects); pyridoxine: 8-12 hours; clinical note: delayed-release formulation maintains therapeutic levels overnight. |
10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride orally once daily at bedtime, increased to twice daily (one tablet at bedtime and one in the morning) up to a maximum of 4 tablets daily (one in the morning, one in the mid-afternoon, and two at bedtime).
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | eGFR 15-29 mL/min/1.73 m²: Maximum 2 tablets daily (20 mg doxylamine/20 mg pyridoxine). eGFR <15 mL/min/1.73 m² or dialysis: Not recommended. |
| Liver impairment | Child-Pugh Class B: Maximum 2 tablets daily. Child-Pugh Class C: Not recommended. |
| Pediatric use | Not FDA-approved for patients <18 years of age; no established pediatric dosing. |
| Geriatric use | Not recommended in patients ≥65 years due to increased risk of anticholinergic effects and cognitive decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DICLEGIS (DICLEGIS).
| Breastfeeding | Both doxylamine and pyridoxine are excreted into breast milk in small quantities. Doxylamine M/P ratio: approximately 0.5; pyridoxine M/P ratio: approximately 1.0. The American Academy of Pediatrics considers doxylamine/pyridoxine compatible with breastfeeding. However, monitor infant for sedation or irritability, especially with high maternal doses. |
| Teratogenic Risk | DICLEGIS (doxylamine/pyridoxine) is classified as FDA Pregnancy Category A. No teratogenic effects have been observed in humans; available data from cohort studies and meta-analyses do not demonstrate increased risk of congenital malformations in the first trimester. Use in second and third trimesters is considered safe; no fetal risks have been associated. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to doxylamine, pyridoxine, or any component","Concomitant use with monoamine oxidase inhibitors (MAOIs) due to risk of hypertensive crisis","Narrow-angle glaucoma","Urinary retention","Peptic ulcer (stenosing)","Asthma attack (acute)"]
| Precautions | ["CNS depression: may cause drowsiness, avoid driving or operating machinery","Concomitant use with other CNS depressants (e.g., alcohol, sedatives) may enhance sedation","Use with caution in patients with asthma, increased intraocular pressure, glaucoma, urinary retention, or gastrointestinal obstruction","Pyridoxine: high doses may cause peripheral neuropathy"] |
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| Fetal Monitoring | No specific fetal monitoring required. Maternal monitoring: assess for anticholinergic effects (e.g., dry mouth, blurred vision, urinary retention) and sedation. If used in pregnancy, standard prenatal care should be continued. |
| Fertility Effects | No known adverse effects on fertility. Doxylamine/pyridoxine is not associated with impairment of male or female fertility based on available data. No studies have specifically evaluated fertility; clinical evidence suggests no negative impact. |