VASERETIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VASERETIC (VASERETIC).
Vaseretic is a combination of enalapril maleate (an angiotensin-converting enzyme inhibitor) and hydrochlorothiazide (a thiazide diuretic). Enalapril inhibits ACE, reducing angiotensin II formation, decreasing aldosterone secretion, and lowering blood pressure. Hydrochlorothiazide increases sodium and chloride excretion by inhibiting the Na+-Cl- symporter in the distal convoluted tubule, leading to diuresis and vasodilation.
| Metabolism | Enalapril is hydrolyzed in the liver to its active metabolite enalaprilat; further metabolism is minor. Hydrochlorothiazide is not metabolized and is excreted unchanged in urine. |
| Excretion | Renal: 60% (enalaprilat); biliary/fecal: 33% (enalaprilat). Unchanged enalapril: <5% in urine. |
| Half-life | Enalaprilat: 35–38 hours (terminal). Clinically, effective half-life ~11 hours. Prolonged in renal impairment (CrCl <30 mL/min: up to 60 hours). |
| Protein binding | Enalapril: <50%; enalaprilat: 50–60% (primarily to albumin). |
| Volume of Distribution | Enalaprilat: 1.2–1.7 L/kg. Indicates extensive extravascular distribution. |
| Bioavailability | Enalapril: 60% (oral, absorption not affected by food). Enalaprilat: Not absorbed orally (given IV or formed via hepatic hydrolysis). |
| Onset of Action | Oral: 1 hour (peak ACE inhibition). IV: 15 minutes. |
| Duration of Action | 24 hours (once-daily dosing for hypertension). Peak effect: 4–6 hours post-dose. |
| Molecular Weight | Enalapril maleate: 492.5 Da; Hydrochlorothiazide: 297.7 Da |
One tablet (10 mg enalapril maleate/25 mg hydrochlorothiazide) orally once daily; may increase to 2 tablets daily if needed.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-60 mL/min: maximum dose 10 mg enalapril/25 mg hydrochlorothiazide daily. For GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: initiate at 5 mg enalapril/12.5 mg hydrochlorothiazide or 10 mg/12.5 mg, titrate cautiously. |
| Pediatric use | Not indicated for pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at lower doses (e.g., 5 mg enalapril/12.5 mg hydrochlorothiazide) due to increased risk of hypotension and electrolyte imbalances; titrate slowly. |
| 1st trimester | Drugs acting directly on the renin-angiotensin system (RAS) can cause fetal renal dysfunction, oligohydramnios, and skull ossification defects. Use is not recommended during the first trimester unless no alternative is available. |
| 2nd trimester | Use is contraindicated in the second trimester due to risk of fetal renal impairment, oligohydramnios, and neonatal anuria. |
| 3rd trimester | Use is contraindicated in the third trimester as exposure is associated with fetal renal dysfunction, oligohydramnios, pulmonary hypoplasia, and neonatal death. |
Clinical note
Comprehensive clinical and safety monograph for VASERETIC (VASERETIC).
| Placental transfer | Both components (enalapril and hydrochlorothiazide) cross the placenta. Enalaprilat, the active metabolite, has been detected in cord blood, and thiazides are known to cross the placental barrier. |
| Breastfeeding | Enalapril is excreted into breast milk in low concentrations; however, effects on the nursing infant are unknown. Hydrochlorothiazide is also excreted into breast milk and may suppress lactation. Use during breastfeeding is not recommended, especially in neonates or preterm infants. |
■ FDA Black Box Warning
WARNING: FETAL TOXICITY. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue Vaseretic as soon as possible once pregnancy is detected.
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyAnuriaSensitivity to sulfonamide-derived drugs (hydrochlorothiazide)Pregnancy (especially second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR <60 mL/min)
| Precautions | Fetal toxicity: Discontinue if pregnancy is detected, Angioedema, including laryngeal edema, can occur; monitor for airway obstruction, Symptomatic hypotension, especially in volume-depleted patients, Renal impairment: Monitor renal function; risk of acute renal failure, Electrolyte imbalances: Hypokalemia, hyponatremia, hypomagnesemia, hypercalcemia, Metabolic acidosis: May occur with hydrochlorothiazide, Impaired hepatic function: Use with caution; risk of hepatic encephalopathy, Systemic lupus erythematosus: May exacerbate or activate SLE, Acute myopia and angle-closure glaucoma: Can occur with hydrochlorothiazide |
| Food/Dietary |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Potential risk of renal and cranial malformations based on human data. Second and third trimesters: Known fetal toxicity including oligohydramnios, fetal renal impairment, skull ossification defects, neonatal hypotension, hyperkalemia, and anuria. Risk increased with prolonged exposure. Avoid unless no alternative. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), potassium levels, urinalysis. Fetal ultrasound for amniotic fluid index, renal anatomy, and growth. Neonatal monitoring for hypotension, hyperkalemia, and renal function after delivery. |
| Fertility Effects | No direct fertility impairment reported in humans. In animal studies, no adverse effects on fertility. However, use in men of reproductive age may rarely affect erectile function. |
| Avoid salt substitutes with potassium; use low-sodium diet cautiously. Grapefruit juice may reduce enalapril absorption; limit intake. Maintain adequate fluid intake; avoid excessive alcohol. Potassium-rich foods (bananas, oranges, spinach) are not restricted unless hyperkalemia develops. |
| Clinical Pearls | VASERETIC (enalapril maleate and hydrochlorothiazide) combines an ACE inhibitor and a thiazide diuretic. Monitor serum potassium, especially in renal impairment or with potassium supplements. Use with caution in patients with bilateral renal artery stenosis. May cause angioedema; discontinue immediately if occurs. Half-life of enalaprilat is ~35 hours with impaired renal function. Initiate therapy with lowest dose to reduce hypotension risk. |
| Patient Advice | Take exactly as prescribed, usually once daily. Swallow tablets whole with water. · If you experience difficulty breathing, swelling of face/lips/tongue, or severe throat tightness, seek emergency medical help immediately (angioedema). · Avoid salt substitutes containing potassium and potassium supplements unless advised by your doctor. · You may feel dizzy, especially during the first few days. Rise slowly from sitting or lying positions. · This medication may cause dry cough. Report persistent cough to your doctor. · Tell all healthcare providers you are taking VASERETIC; it may affect lab tests and surgery. · Drink adequate fluids to prevent dehydration unless instructed otherwise. · Avoid alcohol as it may increase dizziness or hypotension. |