DIUPRES-250
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIUPRES-250 (DIUPRES-250).
| Breastfeeding | Excreted in breast milk; M/P ratio not established; reserpine may cause infant drowsiness, bradycardia, and GI upset; hydrochlorothiazide may decrease milk supply; generally avoid breastfeeding or use with caution. |
| 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. |
■ 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, reserpine, or sulfonamide-derived drugs","Anuria or severe renal impairment","Active peptic ulcer disease or ulcerative colitis","History of major depression or electroconvulsive therapy","Concurrent use with MAO inhibitors (MAOIs) or within 14 days of discontinuation","Pheochromocytoma (reserpine may cause paradoxical hypertension)","Electroconvulsive therapy (relative contraindication due to risk of prolonged seizure or apnea)"]
| 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"] |
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| 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. |