DIUPRES-500
Clinical safety rating
cautionComprehensive 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). |
| Molecular Weight | Methyldopa: 211.22 Da; Chlorothiazide: 295.72 Da; Combination: Average 253.47 Da (weighted by molar ratio) |
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 | Avoid use during first trimester; risk of fetal malformations including neural tube defects and cardiovascular anomalies due to folate antagonism. |
| 2nd trimester | Use only if clearly needed; may cause oligohydramnios and fetal renal impairment. |
| 3rd trimester | Avoid; risk of neonatal thrombocytopenia, leukopenia, and kernicterus due to bilirubin displacement. |
Clinical note
Comprehensive clinical and safety monograph for DIUPRES-500 (DIUPRES-500).
| Placental transfer | Both methyldopa and chlorothiazide cross the placenta. Methyldopa reaches fetal plasma levels approximately 80% of maternal levels; chlorothiazide crosses but data limited. |
| Breastfeeding | Diupres-500 (methyldopa 250 mg + chlorothiazide 250 mg) is excreted in breast milk in low amounts. Methyldopa levels are insufficient to affect the infant; chlorothiazide may suppress lactation. Monitor infant for potential adverse effects such as electrolyte imbalance or thrombocytopenia. |
| Lactation Rating | L3 (Moderately Safe) - Compatible with caution, but consider alternatives. |
| 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 | 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to methyldopa, chlorothiazide, or sulfonamidesActive hepatic disease (e.g., hepatitis, cirrhosis) or history of liver disorders due to methyldopaAnuria or severe renal impairment (creatinine clearance <30 mL/min)Concomitant therapy with MAO inhibitors
| 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 |
| Food/Dietary | Avoid excessive intake of high-potassium foods (e.g., bananas, oranges, spinach) due to increased potassium retention risk with hydrochlorothiazide. Limit alcohol consumption as it may enhance blood pressure-lowering effects and cause dizziness. Maintain adequate hydration but avoid potassium-containing salt substitutes. |
| Clinical Pearls | DIUPRES-500 contains hydrochlorothiazide 50 mg and reserpine 0.125 mg. Monitor serum potassium and renal function regularly. Reserpine may cause bradycardia and depression; use with caution in patients with history of peptic ulcer disease. Avoid abrupt discontinuation due to risk of withdrawal hypertension. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily in the morning. · Do not stop taking this medication suddenly without consulting your doctor. · This drug may make you urinate more frequently; avoid taking it before bedtime. · Report any symptoms of depression, unusual fatigue, or slow heart rate to your doctor. · Avoid prolonged sun exposure and use sunscreen; this medication can increase sensitivity to sunlight. |
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