HYDROPRES 50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYDROPRES 50 (HYDROPRES 50).
Hydrochlorothiazide is a thiazide diuretic that inhibits the sodium-chloride cotransporter in the distal convoluted tubule, increasing excretion of sodium, chloride, and water. Reserpine is a rauwolfia alkaloid that depletes catecholamines and serotonin from central and peripheral nerve endings, reducing sympathetic outflow and lowering blood pressure. The combination provides additive antihypertensive effect.
| Metabolism | Hydrochlorothiazide is not extensively metabolized; eliminated unchanged by the kidneys. Reserpine is extensively metabolized in the liver, primarily via hydrolysis and glucuronidation. |
| Excretion | Hydrochlorothiazide: 95% renal (65% unchanged); Reserpine: 30% renal, 60% fecal |
| Half-life | Hydrochlorothiazide: 6-15 hr (terminal); Reserpine: 50-100 hr (terminal, biphasic). Clinical: HCTZ half-life prolonged in renal impairment; reserpine accumulates with repetitive dosing. |
| Protein binding | Hydrochlorothiazide: 40-68% bound (albumin); Reserpine: 95% bound (alpha-1 acid glycoprotein, albumin). |
| Volume of Distribution | Hydrochlorothiazide: 0.8 L/kg; Reserpine: 12 L/kg (large Vd reflects extensive tissue binding, especially CNS). |
| Bioavailability | Hydrochlorothiazide: 65-75% oral (saturable absorption with food); Reserpine: 50% oral (extensive first-pass metabolism). |
| Onset of Action | Hydrochlorothiazide: oral diuresis 2 hr; Reserpine: oral antihypertensive effect 3-6 days (slow onset due to CNS catecholamine depletion). |
| Duration of Action | Hydrochlorothiazide: diuresis 6-12 hr; Reserpine: antihypertensive effect persists 1-6 weeks after discontinuation (prolonged due to irreversible binding to amine granules). |
| Molecular Weight | Enalapril maleate: 492.5 Da; Hydrochlorothiazide: 297.7 Da |
HYDROPRES 50 is a fixed-dose combination of hydrochlorothiazide 50 mg and reserpine 0.125 mg. Usual adult dose: one tablet orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). For CrCl 30-50 mL/min, use with caution; no specific dose adjustment available. Monitor renal function. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose adjustment available. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate with lower doses (e.g., half tablet) due to increased sensitivity and risk of hypotension, electrolyte imbalance, and CNS effects. Monitor closely. |
| 1st trimester | Avoid; associated with fetal abnormalities (neural tube defects, cleft palate) due to ACE inhibitor component (enalapril) and thiazide diuretic (hydrochlorothiazide). |
| 2nd trimester | Avoid; risk of fetal hypotension, anuria, and oligohydramnios from ACE inhibitor; thiazides may cause electrolyte imbalances. |
| 3rd trimester | Avoid; high risk of neonatal renal failure, hypotension, and death from ACE inhibitor; thiazides can cause thrombocytopenia and electrolyte disturbances. |
Clinical note
Comprehensive clinical and safety monograph for HYDROPRES 50 (HYDROPRES 50).
| Placental transfer | Both components cross placenta; enalaprilat (active metabolite) has significant transfer; hydrochlorothiazide crosses freely and accumulates in fetal serum. |
| Breastfeeding | Not recommended; enalapril and hydrochlorothiazide are excreted in breast milk. Thiazides may suppress lactation and cause electrolyte abnormalities in infant. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHistory of angioedema related to ACE inhibitorsAnuriaHypersensitivity to enalapril or hydrochlorothiazideSulfonamide allergy (cross-reactivity with hydrochlorothiazide)
| Precautions | Reserpine: May cause mental depression, peptic ulcer activation, and bradycardia. Abrupt withdrawal may precipitate severe hypertension. Hydrochlorothiazide: Electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia), hyperuricemia, hypercalcemia, photosensitivity, and acute angle-closure glaucoma. May exacerbate renal impairment. Sulfonamide cross-sensitivity. |
| Food/Dietary | Avoid high-sodium foods and excessive potassium intake. Limit alcohol use. Grapefruit juice may alter metabolism of reserpine. Maintain adequate fluid intake unless fluid-restricted. |
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| Lactation Rating | L4 (Contraindicated) |
| Teratogenic Risk | First trimester: associated with congenital malformations (neural tube defects, cardiovascular anomalies). Second and third trimesters: fetal oliguria, oligohydramnios, pulmonary hypoplasia, skull ossification defects, neonatal hypotension, renal failure, hyperkalemia, death. |
| Fetal Monitoring | Maternal: blood pressure, serum electrolytes, renal function, uric acid, glucose. Fetal: ultrasound for amniotic fluid volume, fetal growth, and anatomy (if first trimester exposure). Neonatal: observe for hypotension, electrolyte disturbances, respiratory depression. |
| Fertility Effects | Hydrochlorothiazide may cause reversible sexual dysfunction in males. Reserpine can impair ejaculation and libido. No definitive evidence of female fertility impairment. Use may affect reproductive capacity. |
| Clinical Pearls | HYDROPRES 50 is a fixed-dose combination of hydrochlorothiazide 50 mg and reserpine 0.125 mg. Reserpine depletes catecholamines, causing orthostatic hypotension and nasal congestion. Onset of antihypertensive effect is slow (2-3 weeks). Avoid in patients with a history of depression, peptic ulcer, or pheochromocytoma. Monitor for electrolyte imbalances (hypokalemia, hyponatremia) and hyperuricemia due to thiazide component. |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · Rise slowly from sitting or lying to prevent dizziness from low blood pressure. · Avoid alcohol and other depressants as they may worsen drowsiness or hypotension. · Report signs of depression, unusual tiredness, slow heartbeat, or swelling. · Do not stop suddenly; abrupt discontinuation may cause severe hypertension. |