DIUTENSEN-R
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 448.5 |
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 | Avoid in first trimester: associated with congenital malformations, including neural tube defects and cardiovascular anomalies. |
| 2nd trimester | Use with caution: may cause fetal hypotension, decreased placental perfusion, and growth restriction. |
| 3rd trimester | Avoid: risk of neonatal hypotension, hypoglycemia, bradycardia, and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for DIUTENSEN-R (DIUTENSEN-R).
| Placental transfer | Crosses placenta; fetal plasma levels are approximately 50-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; potential for infant hypotension and bradycardia. Monitor infant for adverse effects. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to reserpine or any componentHistory of depressionActive peptic ulcerUlcerative colitisElectroconvulsive therapy
| 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. |
| Food/Dietary | Avoid high-sodium foods to enhance antihypertensive effect. Grapefruit juice may increase hydralazine absorption; limit intake. Alcohol can exacerbate orthostatic hypotension. Maintain adequate potassium intake (bananas, oranges) unless otherwise instructed. |
| Clinical Pearls | DIUTENSEN-R is a fixed-dose combination of reserpine, hydralazine, and hydrochlorothiazide. Monitor for orthostatic hypotension, especially at initiation. Reserpine may cause nasal congestion and depression; avoid in patients with history of depression. Hydralazine can induce lupus-like syndrome; obtain ANA titers if symptoms develop. Hydrochlorothiazide may cause electrolyte disturbances; check serum potassium and magnesium periodically. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly. · Rise slowly from sitting or lying to prevent dizziness. · Report any signs of depression, unusual bruising, or joint pain. · Avoid excessive sunlight; use sunscreen. · Do not take over-the-counter cold medications without consulting your doctor. |
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