VASERETIC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VASERETIC (VASERETIC).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VASERETIC (VASERETIC).

Breastfeeding	Very low excretion into breast milk (M/P ratio approximately 0.02). However, due to risk of neonatal hypotension and renal dysfunction, use with caution, especially in preterm or hypotensive infants. Alternative agents preferred.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of angioedema related to previous ACE inhibitor therapy","Hypersensitivity to enalapril, hydrochlorothiazide, or sulfonamide-derived drugs","Anuria","Concomitant use with aliskiren in patients with diabetes (type 1 or 2) or moderate to severe renal impairment (GFR <60 mL/min)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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VASERETIC

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VASERETIC (VASERETIC).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VASERETIC (VASERETIC).

Breastfeeding	Very low excretion into breast milk (M/P ratio approximately 0.02). However, due to risk of neonatal hypotension and renal dysfunction, use with caution, especially in preterm or hypotensive infants. Alternative agents preferred.
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.