MODERIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MODERIL (MODERIL).
Reserpine is an alkaloid that depletes catecholamines (norepinephrine, dopamine) and serotonin from central and peripheral nerve endings by irreversibly binding to and inhibiting the vesicular monoamine transporter (VMAT), preventing storage and leading to degradation by monoamine oxidase.
| Metabolism | Extensively metabolized in the liver via hydrolysis and conjugation; cytochrome P450 (CYP) enzymes not majorly involved. |
| Excretion | Renal: 60% (mainly as unchanged drug); biliary/fecal: ~40% (includes glucuronide conjugates). |
| Half-life | Terminal elimination half-life: 2.5–3.5 hours; may be prolonged to 6–8 hours in severe renal impairment. |
| Protein binding | 50–70% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Vd: 2–4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 50–70% (first-pass effect); IM: 100%; IV: 100%. |
| Onset of Action | IM: 15–30 minutes; IV: 5–10 minutes; oral: 30–60 minutes. |
| Duration of Action | IM/IV: 1–2 hours; oral: 4–6 hours; antihypertensive effect persists 6–12 hours with controlled-release formulation. |
1-10 mg orally twice daily, titrate to effect.
| Dosage form | TABLET |
| Renal impairment | GFR <30 mL/min: reduce dose by 50%; GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | 0.1-0.5 mg/kg/day divided every 12 hours, max 10 mg/day. |
| Geriatric use | Initiate at 1 mg once daily, titrate slowly; monitor for hypotension and sedation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MODERIL (MODERIL).
| Breastfeeding | Unknown M/P ratio; excreted in breast milk in small amounts (approx 1% of maternal weight-adjusted dose). Monitor infant for hypotonia, drowsiness, and poor feeding; avoid if infant has known cardiovascular instability. |
| Teratogenic Risk | Category C. First trimester: insufficient data; animal studies show embryotoxicity at high doses. Second/third trimesters: risk of fetal hypotension and renal impairment due to maternal hypotension; may reduce uteroplacental perfusion. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to reserpine","History of mental depression (especially suicidal tendencies)","Active peptic ulcer","Ulcerative colitis","Electroconvulsive therapy within 7 days","Pheochromocytoma"]
| Precautions | ["Mental depression, especially in patients with history of depression","Peptic ulcer disease exacerbation","Electroconvulsive therapy (ECT) use caution due to severe reactions","Biliary colic in patients with gallstones","Surgery: increased susceptibility to hypotension and bradycardia"] |
Loading safety data…
| Maternal: blood pressure (sitting and standing) q1-2h initially, heart rate, signs of hypotension/syncope. Fetal: serial ultrasound for growth restriction (if used in 2nd/3rd trimesters), nonstress test or biophysical profile if preeclampsia risk; monitor for fetal bradycardia after maternal dosing. |
| Fertility Effects | No formal studies; animal data show no impairment of fertility at therapeutic doses. Postulated: alpha-1 blockade may affect ejaculatory function in males, but no evidence of altered spermatogenesis or impact on female fertility. |