DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE (DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE).

How it works

Doxylamine succinate is a histamine H1 receptor antagonist with sedative properties; pyridoxine hydrochloride is a vitamin B6 derivative that acts as a coenzyme in amino acid, carbohydrate, and lipid metabolism. The combination is believed to reduce nausea and vomiting through central anticholinergic effects and pyridoxine supplementation.

What the body does with it

Metabolism	Doxylamine: extensively metabolized in the liver via N-demethylation and N-acetylation; pyridoxine: converted to pyridoxal phosphate in the liver.
Excretion	Doxylamine: ~60% renal as unchanged drug and metabolites; Pyridoxine: primarily renal as 4-pyridoxic acid and other metabolites. Up to 70% of pyridoxine metabolites excreted in urine within 24 hours.
Half-life	Doxylamine: terminal half-life 10-12 hours; steady state reached in 3-4 days. Pyridoxine: half-life 15-20 days for body stores, but plasma half-life of pyridoxal phosphate ~15-30 minutes.
Protein binding	Doxylamine: ~75-85% bound to plasma proteins (albumin). Pyridoxine: largely unbound; pyridoxal phosphate bound to albumin (~50-80%).
Volume of Distribution	Doxylamine: apparent Vd ~3-4 L/kg, indicating extensive tissue distribution. Pyridoxine: Vd ~0.6 L/kg for pyridoxine; much larger for its phosphate esters.
Bioavailability	Oral doxylamine: ~80-90% absorbed; extensive first-pass metabolism reduces bioavailability to ~25-50% for parent drug. Pyridoxine: oral bioavailability ~80-90%.
Onset of Action	Oral: doxylamine onset of antiemetic effect within 30-60 minutes; peak sedation at 1-2 hours.
Duration of Action	Oral: antiemetic and sedative duration ~6-8 hours; clinical effect for nausea persists throughout dosing interval (nightly dosing).

Classification & Brands

Dosing & administration

1 tablet (doxylamine succinate 10 mg / pyridoxine hydrochloride 10 mg) orally twice daily (morning and evening), increased to three times daily if needed (one tablet in the morning, one in the afternoon, and two at bedtime). Maximum: 4 tablets per day.

Dosage form	TABLET, DELAYED RELEASE
Renal impairment	GFR 30-50 mL/min: Use with caution; no specific dose adjustment recommended. GFR <30 mL/min or dialysis: Avoid use due to lack of data and potential for accumulation.
Liver impairment	Child-Pugh Class A and B: No dose adjustment recommended. Child-Pugh Class C: Use with caution; consider dose reduction or alternative therapy.
Pediatric use	Not recommended for use in pediatric patients (<18 years) for nausea and vomiting of pregnancy; safety and efficacy not established.
Geriatric use	Use with caution due to increased sensitivity to anticholinergic effects (e.g., confusion, constipation, urinary retention). Consider lower starting dose if clinically appropriate; monitor closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE (DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE).

Breastfeeding	Both doxylamine and pyridoxine are excreted into breast milk in low amounts. The milk-to-plasma ratio (M/P) for doxylamine is approximately 1.4–1.6; for pyridoxine, it is higher but pyridoxine is an essential vitamin. Infant exposure is considered low and unlikely to cause adverse effects. Caution is advised; monitor infant for sedation.
Teratogenic Risk	FDA Pregnancy Category A (original) or not assigned for all trimesters. Studies indicate no increased risk of major malformations. First trimester: no significant teratogenicity observed. Second and third trimesters: considered safe; no known fetal adverse effects.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to doxylamine, pyridoxine, or any component","MAO inhibitor use (concurrent or within 14 days)","Acute porphyria"]

Clinical Precautions

Precautions	["CNS depression: may cause drowsiness, avoid alcohol and other sedatives","Anticholinergic effects: use with caution in patients with asthma, increased intraocular pressure, or urinary retention","Masking of underlying condition: persistent vomiting may indicate serious condition"]
Food/Dietary	No known food interactions. However, taking with food may delay absorption. Avoid alcohol and grapefruit juice as they may increase sedation or side effects.

Clinical Tips & Counseling

Drug interactions

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DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE (DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE).

How it works

What the body does with it

Metabolism	Doxylamine: extensively metabolized in the liver via N-demethylation and N-acetylation; pyridoxine: converted to pyridoxal phosphate in the liver.
Excretion	Doxylamine: ~60% renal as unchanged drug and metabolites; Pyridoxine: primarily renal as 4-pyridoxic acid and other metabolites. Up to 70% of pyridoxine metabolites excreted in urine within 24 hours.
Half-life	Doxylamine: terminal half-life 10-12 hours; steady state reached in 3-4 days. Pyridoxine: half-life 15-20 days for body stores, but plasma half-life of pyridoxal phosphate ~15-30 minutes.
Protein binding	Doxylamine: ~75-85% bound to plasma proteins (albumin). Pyridoxine: largely unbound; pyridoxal phosphate bound to albumin (~50-80%).
Volume of Distribution	Doxylamine: apparent Vd ~3-4 L/kg, indicating extensive tissue distribution. Pyridoxine: Vd ~0.6 L/kg for pyridoxine; much larger for its phosphate esters.
Bioavailability	Oral doxylamine: ~80-90% absorbed; extensive first-pass metabolism reduces bioavailability to ~25-50% for parent drug. Pyridoxine: oral bioavailability ~80-90%.
Onset of Action	Oral: doxylamine onset of antiemetic effect within 30-60 minutes; peak sedation at 1-2 hours.
Duration of Action	Oral: antiemetic and sedative duration ~6-8 hours; clinical effect for nausea persists throughout dosing interval (nightly dosing).

Classification & Brands

Dosing & administration

Dosage form	TABLET, DELAYED RELEASE
Renal impairment	GFR 30-50 mL/min: Use with caution; no specific dose adjustment recommended. GFR <30 mL/min or dialysis: Avoid use due to lack of data and potential for accumulation.
Liver impairment	Child-Pugh Class A and B: No dose adjustment recommended. Child-Pugh Class C: Use with caution; consider dose reduction or alternative therapy.
Pediatric use	Not recommended for use in pediatric patients (<18 years) for nausea and vomiting of pregnancy; safety and efficacy not established.
Geriatric use	Use with caution due to increased sensitivity to anticholinergic effects (e.g., confusion, constipation, urinary retention). Consider lower starting dose if clinically appropriate; monitor closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE (DOXYLAMINE SUCCINATE AND PYRIDOXINE HYDROCHLORIDE).

Breastfeeding	Both doxylamine and pyridoxine are excreted into breast milk in low amounts. The milk-to-plasma ratio (M/P) for doxylamine is approximately 1.4–1.6; for pyridoxine, it is higher but pyridoxine is an essential vitamin. Infant exposure is considered low and unlikely to cause adverse effects. Caution is advised; monitor infant for sedation.
Teratogenic Risk	FDA Pregnancy Category A (original) or not assigned for all trimesters. Studies indicate no increased risk of major malformations. First trimester: no significant teratogenicity observed. Second and third trimesters: considered safe; no known fetal adverse effects.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to doxylamine, pyridoxine, or any component","MAO inhibitor use (concurrent or within 14 days)","Acute porphyria"]

Clinical Precautions

Precautions	["CNS depression: may cause drowsiness, avoid alcohol and other sedatives","Anticholinergic effects: use with caution in patients with asthma, increased intraocular pressure, or urinary retention","Masking of underlying condition: persistent vomiting may indicate serious condition"]
Food/Dietary	No known food interactions. However, taking with food may delay absorption. Avoid alcohol and grapefruit juice as they may increase sedation or side effects.

Clinical Tips & Counseling

Drug interactions

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