DIUPRES-250
Clinical safety rating
cautionComprehensive clinical and safety monograph for DIUPRES-250 (DIUPRES-250).
Diupres-250 is a combination of hydrochlorothiazide (a thiazide diuretic) and reserpine (a Rauwolfia alkaloid). Hydrochlorothiazide inhibits the Na+/Cl- cotransporter in the distal convoluted tubule of the kidney, increasing excretion of sodium and water. Reserpine depletes catecholamines and serotonin from presynaptic nerve terminals by irreversibly binding to vesicular monoamine transporter (VMAT), leading to reduced sympathetic outflow and hypotension.
| Metabolism | Hydrochlorothiazide is not metabolized; excreted unchanged by the kidneys. Reserpine undergoes extensive hepatic metabolism via CYP3A4 oxidation. |
| Excretion | Renal: approximately 50% of hydroflumethiazide is excreted unchanged in urine; reserpine is extensively metabolized with <1% excreted unchanged. Fecal: minimal. |
| Half-life | Hydroflumethiazide: 6-18 hours (prolonged in renal impairment). Reserpine: 50-100 hours (biphasic; terminal phase). |
| Protein binding | Hydroflumethiazide: 75-80% bound to plasma proteins. Reserpine: approximately 95% bound (primarily to albumin). |
| Volume of Distribution | Hydroflumethiazide: 3-8 L/kg (extensive distribution). Reserpine: 9-12 L/kg (highly lipid-soluble, crosses blood-brain barrier). |
| Bioavailability | Oral: hydroflumethiazide ~70% (variability); reserpine ~40% (first-pass metabolism). |
| Onset of Action | Oral: hypotensive effect of reserpine begins in 3-6 days; diuretic effect of hydroflumethiazide starts within 2 hours, peak at 4-6 hours. |
| Duration of Action | Reserpine: up to 3-4 weeks after chronic dosing (cumulative effect). Hydroflumethiazide: 6-12 hours for diuresis; antihypertensive effect persists longer with repeated use. |
| Molecular Weight | 482.61 |
1 tablet (containing 250 mg chlorothiazide and 0.125 mg reserpine) orally once daily, increased to 2 tablets daily if needed.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min. For GFR 30-60 mL/min: use 1 tablet every other day; avoid if GFR <30 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% or increase dosing interval. Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for pediatric use due to reserpine component; safety and efficacy not established. |
| Geriatric use | Initiate at 1 tablet every other day; monitor for electrolyte disturbances, orthostatic hypotension, and central nervous system effects. |
| 1st trimester | Contraindicated in the first trimester due to risk of fetal hypotension, renal hypoperfusion, and oligohydramnios. May cause fetal harm when administered to a pregnant woman. |
| 2nd trimester | Not recommended. Can cause fetal and neonatal morbidity and death. Use only if potential benefit justifies risk to fetus. |
| 3rd trimester | Contraindicated in the third trimester due to risk of fetal and neonatal hypotension, anuria, hyperkalemia, and skull ossification defects. |
Clinical note
Comprehensive clinical and safety monograph for DIUPRES-250 (DIUPRES-250).
| Placental transfer | Crosses the placenta in mice and rats. In humans, limited data suggest low transfer; however, fetal exposure likely due to potential for fetal harm. |
| Breastfeeding | Excreted into human milk in small amounts; however, effects on nursing infant are unknown. Use with caution, especially in preterm or jaundiced infants. Monitor infant for hypotension and renal function. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Use cautiously due to potential fetal bradycardia from the reserpine component; second and third trimesters: Risk of fetal hypotension, bradycardia, and hypothermia; reserpine crosses placenta and may cause neonatal respiratory depression and nasal congestion. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, electrolytes, and renal function; fetal monitoring for bradycardia and growth restriction; neonatal surveillance for hypotension and bradycardia after delivery. |
| Fertility Effects | Reserpine may impair libido and cause ejaculatory dysfunction in males; hydrochlorothiazide may cause electrolyte disturbances that could theoretically affect fertility; no direct evidence of impaired fertility in females. |
■ FDA Black Box Warning
No FDA black box warning identified. Reserpine use may be associated with increased risk of breast cancer (historical concern, not confirmed), but no official boxed warning.
| Serious Effects |
Hypersensitivity to hydrochlorothiazide or reserpineAnuriaActive peptic ulcerUlcerative colitisHistory of mental depressionElectroshock therapyPheochromocytomaSevere hepatic impairment
| Precautions | Electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia), Hyperuricemia and gout, Increased blood urea nitrogen (BUN) and creatinine, Photosensitivity with thiazides, Mental depression with reserpine (history of depression, suicidal ideation), Bradycardia, hypotension, and sedation with reserpine, Exacerbation of peptic ulcer disease (reserpine increases gastric acid secretion), Possible withdrawal syndromes (severe hypertension, tachycardia) upon abrupt discontinuation |
| Food/Dietary | Avoid high-sodium foods to enhance antihypertensive effect. Alcohol may increase orthostatic hypotension. Grapefruit juice may alter reserpine metabolism (caution). Avoid tyramine-rich foods (e.g., aged cheeses, cured meats) if also taking MAOIs, but not typically required with reserpine alone. Maintain adequate potassium intake (bananas, oranges) due to hydrochlorothiazide-induced potassium loss. |
| Clinical Pearls | DIUPRES-250 (hydrochlorothiazide 25 mg / reserpine 0.125 mg) is a fixed-dose combination antihypertensive. Reserpine depletes catecholamines, causing orthostatic hypotension and nasal congestion. Hydrochlorothiazide may cause hypokalemia, hyperglycemia, and photosensitivity. Avoid in patients with history of depression (reserpine). Monitor serum potassium, glucose, and uric acid. Onset of full effect may take weeks due to reserpine. |
| Patient Advice | Take this medication exactly as prescribed, at the same time each day. · Stand up slowly to avoid dizziness or fainting. · Expect nasal congestion which may improve over time. · Use sunscreen and protective clothing to avoid sunburn. · Do not stop abruptly without consulting your doctor (risk of severe hypertension). · Report any mood changes, breast tenderness, or abdominal pain to your doctor. · Avoid driving or operating machinery until you know how this medicine affects you. |
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