RAUWOLFIA SERPENTINA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RAUWOLFIA SERPENTINA (RAUWOLFIA SERPENTINA).

How it works

Rauwolfia serpentina alkaloids (e.g., reserpine) deplete catecholamines and serotonin from central and peripheral neurons by binding irreversibly to vesicular monoamine transporters (VMAT), leading to reduced sympathetic outflow and decreased blood pressure.

What the body does with it

Metabolism	Hepatic metabolism via CYP450 enzymes, with active metabolites (e.g., reserpine is metabolized by hydrolysis and conjugation); significant first-pass effect.
Excretion	Renal (urinary) elimination of unchanged drug and metabolites: approximately 60-70% as metabolites, <1% unchanged. Fecal excretion: 30-40% via bile.
Half-life	Terminal elimination half-life: 40-100 hours (mean ~70 h). Accumulation occurs with chronic dosing; steady-state reached in ~2-3 weeks.
Protein binding	Plasma protein binding: approximately 80-90%, primarily to alpha1-acid glycoprotein and albumin.
Volume of Distribution	Vd: 0.5-1.0 L/kg. High tissue distribution, especially to adipose tissue and brain, correlating with extensive accumulation.
Bioavailability	Oral bioavailability: approximately 50% (range 30-60%) due to first-pass metabolism. Not administered parenterally in clinical practice.
Onset of Action	Oral: 2-4 weeks for full antihypertensive effect; initial effects may be seen in 1-2 weeks. IV: not clinically used.
Duration of Action	Duration of effect: 6-12 hours after a single oral dose for blood pressure reduction; prolonged effect with chronic dosing due to long half-life. Clinical effect persists for days after discontinuation.

Classification & Brands

Dosing & administration

Oral: 50–100 mg twice daily for 2 weeks, then maintenance of 50–100 mg once daily.

Dosage form	TABLET
Renal impairment	Not studied; avoid use in severe renal impairment (GFR <30 mL/min) due to risk of accumulation and CNS effects.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in Child-Pugh A/B; consider 50% dose reduction.
Pediatric use	Not recommended in children <12 years. For ages ≥12: 100 µg/kg twice daily, max 50 mg/dose.
Geriatric use	Start at lowest dose (50 mg once daily) and titrate slowly; monitor for CNS depression, orthostatic hypotension, and depression.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for RAUWOLFIA SERPENTINA (RAUWOLFIA SERPENTINA).

Breastfeeding	Rauwolfia alkaloids (reserpine) are excreted into breast milk. M/P ratio is not established. Avoid breastfeeding due to potential for infant hypotension, bradycardia, and extrapyramidal effects. Alternative therapy recommended.
Teratogenic Risk	Rauwolfia serpentina (reserpine) is Pregnancy Category C. First trimester: Limited human data; animal studies show increased fetal resorptions and skeletal anomalies. Second/third trimesters: May cause neonatal bradycardia, hypotonia, and nasal congestion due to placental transfer. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Active peptic ulcer, ulcerative colitis, history of depression (especially with suicidal tendencies), electroconvulsive therapy, pheochromocytoma, and concomitant MAO inhibitors.

Clinical Precautions

Precautions

Risk of severe depression and suicide; use with caution in patients with history of depression. May cause bradycardia, electrolyte disturbances, and gastrointestinal bleeding. Avoid abrupt discontinuation to prevent withdrawal symptoms. Possible extrapyramidal symptoms and parkinsonism.

Clinical Tips & Counseling

Drug interactions

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RAUWOLFIA SERPENTINA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RAUWOLFIA SERPENTINA (RAUWOLFIA SERPENTINA).

How it works

What the body does with it

Metabolism	Hepatic metabolism via CYP450 enzymes, with active metabolites (e.g., reserpine is metabolized by hydrolysis and conjugation); significant first-pass effect.
Excretion	Renal (urinary) elimination of unchanged drug and metabolites: approximately 60-70% as metabolites, <1% unchanged. Fecal excretion: 30-40% via bile.
Half-life	Terminal elimination half-life: 40-100 hours (mean ~70 h). Accumulation occurs with chronic dosing; steady-state reached in ~2-3 weeks.
Protein binding	Plasma protein binding: approximately 80-90%, primarily to alpha1-acid glycoprotein and albumin.
Volume of Distribution	Vd: 0.5-1.0 L/kg. High tissue distribution, especially to adipose tissue and brain, correlating with extensive accumulation.
Bioavailability	Oral bioavailability: approximately 50% (range 30-60%) due to first-pass metabolism. Not administered parenterally in clinical practice.
Onset of Action	Oral: 2-4 weeks for full antihypertensive effect; initial effects may be seen in 1-2 weeks. IV: not clinically used.
Duration of Action	Duration of effect: 6-12 hours after a single oral dose for blood pressure reduction; prolonged effect with chronic dosing due to long half-life. Clinical effect persists for days after discontinuation.

Classification & Brands

Dosing & administration

Oral: 50–100 mg twice daily for 2 weeks, then maintenance of 50–100 mg once daily.

Dosage form	TABLET
Renal impairment	Not studied; avoid use in severe renal impairment (GFR <30 mL/min) due to risk of accumulation and CNS effects.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in Child-Pugh A/B; consider 50% dose reduction.
Pediatric use	Not recommended in children <12 years. For ages ≥12: 100 µg/kg twice daily, max 50 mg/dose.
Geriatric use	Start at lowest dose (50 mg once daily) and titrate slowly; monitor for CNS depression, orthostatic hypotension, and depression.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for RAUWOLFIA SERPENTINA (RAUWOLFIA SERPENTINA).

Breastfeeding	Rauwolfia alkaloids (reserpine) are excreted into breast milk. M/P ratio is not established. Avoid breastfeeding due to potential for infant hypotension, bradycardia, and extrapyramidal effects. Alternative therapy recommended.
Teratogenic Risk	Rauwolfia serpentina (reserpine) is Pregnancy Category C. First trimester: Limited human data; animal studies show increased fetal resorptions and skeletal anomalies. Second/third trimesters: May cause neonatal bradycardia, hypotonia, and nasal congestion due to placental transfer. Use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Active peptic ulcer, ulcerative colitis, history of depression (especially with suicidal tendencies), electroconvulsive therapy, pheochromocytoma, and concomitant MAO inhibitors.