DIUPRES-500
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIUPRES-500 (DIUPRES-500).
Diupres-500 is a combination of chlorothiazide, a thiazide diuretic, and reserpine, a Rauwolfia alkaloid. Chlorothiazide inhibits the Na+-Cl- symporter in the distal convoluted tubule of the kidney, reducing sodium and chloride reabsorption and increasing water excretion. Reserpine depletes catecholamines from central and peripheral nerve terminals by blocking vesicular monoamine transporter 2 (VMAT2), leading to decreased sympathetic outflow and vasodilation.
| Metabolism | Chlorothiazide is not metabolized and is excreted unchanged in urine. Reserpine is extensively metabolized in the liver via CYP450 enzymes to inactive metabolites. |
| Excretion | Renal: ~50% (primarily hydrochlorothiazide), Fecal: ~50% (primarily reserpine). |
| Half-life | Reserpine: 50-100 hours (prolonged; clinical effect persists for days due to irreversible MAO depletion). Hydrochlorothiazide: 6-15 hours (biphasic; terminal phase reflects renal elimination). |
| Protein binding | Reserpine: ~96% (albumin). Hydrochlorothiazide: ~68% (albumin). |
| Volume of Distribution | Reserpine: 4-8 L/kg (extensive tissue binding, especially lipid-rich and CNS). Hydrochlorothiazide: 0.8-1.5 L/kg (distributes into extracellular fluid). |
| Bioavailability | Oral: Reserpine ~50% (variable due to first-pass metabolism); Hydrochlorothiazide ~65-70% (dose-dependent). |
| Onset of Action | Oral: Reserpine 3-6 days (full antihypertensive effect); Hydrochlorothiazide 2 hours (diuresis). |
| Duration of Action | Reserpine: 1-2 weeks (after discontinuation, due to slow recovery of catecholamine stores). Hydrochlorothiazide: 6-12 hours (diuretic effect). |
Oral, 1 tablet (hydrochlorothiazide 50 mg + reserpine 0.125 mg) once daily, increased up to 2 tablets per day if needed.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: use with caution, reduce dose if needed. GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: contraindicated due to risk of hepatic encephalopathy. |
| Pediatric use | Not recommended; safety and efficacy not established. |
| Geriatric use | Initiate at lowest dose (50 mg hydrochlorothiazide + 0.125 mg reserpine) once daily; monitor electrolytes, renal function, and CNS depression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIUPRES-500 (DIUPRES-500).
| Breastfeeding | Excreted in breast milk; M/P ratio approximately 0.2-0.4. Consider risk of infant sedation and poor feeding. Weigh benefits of breastfeeding against potential adverse effects. |
| Teratogenic Risk | First trimester: Risk of fetal hydantoin syndrome (craniofacial defects, hypoplastic nails, growth deficiency). Second trimester: Increased risk of neural tube defects, congenital heart defects. Third trimester: Risk of neonatal hemorrhage and hepatic enzyme induction. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to chlorothiazide, reserpine, or sulfonamide-derived drugs","Anuria","Active peptic ulcer disease","Ulcerative colitis","History of mental depression (especially with suicidal tendencies)","Electroconvulsive therapy","Pheochromocytoma"]
| Precautions | ["Electrolyte imbalance: Monitor potassium, sodium, magnesium; hypokalemia increases risk of digitalis toxicity","Mental depression: Reserpine may cause severe depression, especially in patients with history","Sulfonamide cross-sensitivity: Chlorothiazide may cause allergic reactions in patients with sulfonamide allergy","Azotemia: May precipitate renal impairment in patients with kidney disease","Orthostatic hypotension: Common with reserpine, especially after initial doses"] |
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| Monitor maternal phenytoin serum levels (therapeutic range 10-20 μg/mL). Fetal ultrasound for structural anomalies. Assess for neonatal bleeding with vitamin K prophylaxis at birth. Monitor for signs of fetal distress. |
| Fertility Effects | May reduce effectiveness of oral contraceptives due to hepatic enzyme induction. Potential for menstrual irregularities and anovulation. Use alternative contraception methods. |