DIUTENSEN-R
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIUTENSEN-R (DIUTENSEN-R).
DIUTENSEN-R is a combination of reserpine and chlorothiazide. Reserpine depletes catecholamines from peripheral sympathetic nerve endings by inhibiting vesicular monoamine transporter (VMAT), leading to reduced sympathetic tone. Chlorothiazide is a thiazide diuretic that inhibits sodium reabsorption in the distal convoluted tubule, promoting natriuresis and reducing plasma volume.
| Metabolism | Reserpine is extensively metabolized in the liver via CYP450 enzymes; chlorothiazide is not significantly metabolized and is excreted unchanged in urine. |
| Excretion | Renal: 59% (cryptenamine), 50% (methylothiazide), 7% (reserpine); Biliary/fecal: 21% (cryptenamine), 48% (methylothiazide), 90% (reserpine) |
| Half-life | Terminal half-life: cryptenamine 9-10 h, methylothiazide 18-24 h, reserpine 50-100 h (prolonged due to enterohepatic recirculation and tissue binding; accumulation occurs with daily dosing) |
| Protein binding | Methylothiazide: 65-70% bound to albumin; Reserpine: 95% bound to alpha-1-acid glycoprotein and albumin; Cryptenamine: insufficient data |
| Volume of Distribution | Methylothiazide: 0.25-0.3 L/kg (primarily extracellular fluid); Reserpine: 2.5-7 L/kg (extensive tissue binding, especially adipose and brain); Cryptenamine: ~1 L/kg (moderate distribution) |
| Bioavailability | Oral: methylothiazide 90-100%; reserpine 50-60% (first-pass metabolism); cryptenamine 40-60% (variable first-pass) |
| Onset of Action | Oral: antihypertensive effect begins within 1-2 weeks (methylothiazide); 3-6 days (reserpine); 1-2 h (cryptenamine for mild effect) |
| Duration of Action | Oral: 12-24 h (methylothiazide); 14-28 days (reserpine for depletion effect); 6-12 h (cryptenamine). Note: Reserpine effect persists after discontinuation due to irreversible binding to storage vesicles. |
One tablet orally once daily. Each tablet contains 2.5 mg reserpine and 25 mg chlorthalidone.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-50 mL/min: reduce dose by 50%; eGFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh class A: no adjustment; class B or C: contraindicated. |
| Pediatric use | Not recommended for use in children. |
| Geriatric use | Initiate therapy at half the standard adult dose (one-half tablet daily) and titrate cautiously due to increased sensitivity to adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIUTENSEN-R (DIUTENSEN-R).
| Breastfeeding | Reserpine is excreted into breast milk and may cause adverse effects in nursing infants (e.g., nasal congestion, respiratory depression, bradycardia). Hydrochlorothiazide is excreted in small amounts; M/P ratio is approximately 0.6. However, thiazides may suppress lactation. Safety not established; use during breastfeeding is not recommended. |
| Teratogenic Risk | First trimester: Use of reserpine component may be associated with increased risk of congenital malformations, but data are limited. Second and third trimesters: Reserpine can cause neonatal respiratory depression, bradycardia, hypothermia, and nasal congestion; hydrochlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, electrolyte imbalances, and volume depletion. Overall, this combination is classified as pregnancy category C (reserpine) and B (hydrochlorothiazide); avoid use in pregnancy unless benefit outweighs risk. |
■ FDA Black Box Warning
Reserpine component: Risk of mental depression, which may be severe and can lead to suicide. Use with caution in patients with history of depression.
| Serious Effects |
["Active peptic ulcer","Ulcerative colitis","History of mental depression","Electroshock therapy","Anuria","Hypersensitivity to reserpine, chlorothiazide, or sulfonamide-derived drugs"]
| Precautions | ["Monitor for signs of depression; discontinue if depression occurs.","Electrolyte imbalance (hypokalemia, hyponatremia, hypomagnesemia) with chlorothiazide.","Orthostatic hypotension with reserpine.","Use cautiously in patients with peptic ulcer disease, renal impairment, or hepatic impairment."] |
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| Fetal Monitoring | Monitor maternal blood pressure, electrolytes (especially potassium, sodium, magnesium), renal function, and fetal growth (ultrasound) throughout pregnancy. In neonates exposed in utero, monitor for signs of respiratory depression, bradycardia, hypothermia, jaundice, and electrolyte disturbances. |
| Fertility Effects | Reserpine may cause decreased libido and erectile dysfunction in males; effects on female fertility are unknown. Hydrochlorothiazide has no known direct effects on fertility. Data on combined effect are lacking. |