RAUWOLFIA SERPENTINA
Clinical safety rating
cautionComprehensive clinical and safety monograph for RAUWOLFIA SERPENTINA (RAUWOLFIA SERPENTINA).
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.
| 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. |
| Molecular Weight | 608.69 Da (for reserpine, the primary active alkaloid; Rauwolfia serpentina contains multiple alkaloids, but reserpine is the most studied and has this molecular weight) |
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. |
| 1st trimester | Associated with increased risk of congenital malformations, particularly cardiovascular and central nervous system defects; avoid use. |
| 2nd trimester | May cause fetal/neonatal respiratory depression, bradycardia, and hypotension; avoid use. |
| 3rd trimester | Risk of neonatal respiratory depression, bradycardia, hypothermia, and hypotonia; avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for RAUWOLFIA SERPENTINA (RAUWOLFIA SERPENTINA).
| Placental transfer | Crosses the placenta; demonstrated in animal studies and reports of fetal effects in humans. |
| Breastfeeding | Rauwolfia alkaloids are excreted into breast milk. Use is contraindicated during breastfeeding due to potential for adverse effects in the infant, including respiratory depression, bradycardia, and gastrointestinal disturbances. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of depression or extrapyramidal symptoms. In fetus/neonate: monitor for bradycardia, hypotonia, respiratory depression, and nasal congestion. Consider ultrasound for fetal growth if used in pregnancy. |
| Fertility Effects | Reserpine can increase prolactin levels, potentially causing galactorrhea and menstrual irregularities in women, and may impair spermatogenesis in men, reducing fertility. Effects are reversible upon discontinuation. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to Rauwolfia serpentina or its componentsHistory of depression, especially with suicidal tendenciesActive peptic ulcer diseaseUlcerative colitisPheochromocytomaElectroconvulsive therapy (ECT)
| 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. |
| Food/Dietary | Avoid tyramine-rich foods (aged cheeses, cured meats, fermented products) as Rauwolfia may potentiate pressor effects. Limit alcohol intake. No specific food restrictions otherwise; but taking with food may reduce gastrointestinal upset. |
| Clinical Pearls | 1. Rauwolfia serpentina (reserpine) depletes catecholamines and serotonin from central and peripheral nerve endings; onset of action is slow (weeks) and offset prolonged. 2. Use cautiously in patients with history of peptic ulcer disease due to increased gastric acid secretion. 3. May cause significant bradycardia and orthostatic hypotension; monitor blood pressure and heart rate regularly. 4. Avoid concomitant use with MAOIs, tricyclic antidepressants, or sympathomimetics due to risk of hypertensive crisis. 5. Documented nasal congestion and sedation are common; consider alternative antihypertensives if tolerated poorly. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly as this may cause rapid rise in blood pressure. · Rise slowly from sitting or lying down to minimize dizziness from low blood pressure. · Avoid alcohol, which can worsen dizziness and drowsiness. · Report persistent nasal congestion, stomach pain, or unusual tiredness to your doctor. · Use caution when driving or operating machinery until you know how this medication affects you. |
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