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Enalapril Maleate / Hydrochlorothiazide

Pronunciation: en-AL-a-pril MAL-ee-ate/HYE-droe-KLOR-oh-THYE-a-zide
Class: Antihypertensive combination

Trade Names

Enalapril Maleate/Hydrochlorothiazide
- Tablets, oral enalapril maleate 5 mg/hydrochlorothiazide 12.5 mg

- Tablets, oral enalapril maleate 10 mg/hydrochlorothiazide 25 mg

Vaseretic (Canada)



Competitively inhibits angiotensin I–converting enzyme, preventing conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that also stimulates release of aldosterone, resulting in a decrease in BP, reduced sodium absorption, and potassium retention.


Inhibits reabsorption of sodium and chloride in ascending loop of Henle and early distal tubules.

Indications and Usage

For the treatment of hypertension.


Hypersensitivity to any component or to other sulfonamide-derived drugs; history of angioedema related to previous treatment with an ACE inhibitor; hereditary or idiopathic angioedema; anuria.

Dosage and Administration


PO Enalapril 5 mg/hydrochlorothiazide 12.5 mg or enalapril 10 mg/hydrochlorothiazide 25 mg daily initially in patients not adequately controlled with enalapril or hydrochlorothiazide monotherapy. May increase in 2 to 3 wk if needed (max, enalapril 20 mg/hydrochlorothiazide 50 mg).

General Advice

  • May be taken with or without food.
  • Not indicated for initial treatment of hypertension.
  • May be substituted for the titrated components.


Store between 59° and 86°F. Protect from moisture.

Drug Interactions

No drug interaction studies have been conducted between enalapril/hydrochlorothiazide and other drugs. The following interactions are based on drug interactions involving each component of the enalapril/hydrochlorothiazide combination.

Alcohol, barbiturates, narcotics

Potentiation of orthostatic hypotension may occur. Monitor BP.

Aldosterone blockers (eg, eplerenone)

Serious hyperkalemia, possibly with cardiac arrhythmias, may occur. Use with caution and monitor potassium level periodically; reduce the dose of the aldosterone blocker if needed.


May decrease renal excretion of potassium, particularly in diabetic patients. Use alternatives to aliskiren in diabetic patients. If coadministration is undertaken, closely monitor serum potassium.

Angiotensin II receptor antagonists (eg, valsartan)

Coadministration may be associated with an increased risk of renal dysfunction and hyperkalemia. Consider monotherapy. If coadministration cannot be avoided, closely monitor renal function and serum potassium.

Antihypertensive agents (eg, propranolol)

Additive or potentiation of hypotensive effects. Closely monitor BP.

Antineoplastic agents (eg, cyclophosphamide)

Hydrochlorothiazide may prolong antineoplastic-induced myelosuppression. If coadministration cannot be avoided, use with caution.

Cholestyramine, colestipol resins

Hydrochlorothiazide absorption may be impaired. GI absorption may be reduced up to 85%. Separate the administration times by 4 h or more.


May cause excessive decreases in BP and syncope. Consider lower starting dosage of clozapine in patients receiving antihypertensives. Enalapril/hydrochlorothiazide dosage reduction may be needed.

Corticosteroids, corticotropin

Electrolyte depletion may be intensified, particularly hypokalemia. Closely monitor serum potassium.

Cyclooxygenase 2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen)

Coadministration may result in the deterioration of renal function, including acute renal failure, especially in patients with renal impairment or volume depletion, or in elderly patients. In addition, the antihypertensive effects of enalapril/hydrochlorothiazide may be decreased. Monitor BP and the diuretic response; monitor renal function periodically.


Acute renal failure has been reported with coadministration. If renal dysfunction occurs, it may be necessary to stop 1 or both agents.


The pharmacologic effects of both drugs may be increased. Hyperglycemia, hyperuricemia, and hypotension may occur. Closely monitor BP, blood glucose, and serum uric acid.


Hydrochlorothiazide-induced electrolyte disturbances may predispose patients to digitalis-induced arrhythmias. Closely monitor plasma concentrations of potassium and magnesium; supplement low levels. Monitor patients for digoxin toxicity.


Dofetilide plasma concentrations may be increased. Prolongation of the QT interval may occur, increasing the risk of torsades de pointes. Coadministration is contraindicated.

Gold salts (eg, sodium aurothiomalate)

Nitroid reactions (eg, facial flushing, hypotension, nausea, vomiting) have been reported rarely in patients on concomitant ACE inhibitors and injectable gold.

Hypoglycemic agents, oral (eg, sulfonylureas)

Hydrochlorothiazide may increase fasting blood glucose. The effect of oral hypoglycemic agents may be decreased. Monitor blood glucose and adjust the hypoglycemic dose as needed.


Hydrochlorothiazide may increase fasting blood glucose and decrease insulin secretion. The effect of insulin may be decreased. Monitor blood glucose and adjust the insulin dose as needed.


Lithium Cl may be decreased, increasing lithium concentrations and the risk of lithium toxicity. Avoid coadministration. If coadministration cannot be avoided, frequently monitor lithium serum levels and observe the patient for symptoms of lithium toxicity.

Loop diuretics (eg, furosemide)

The effects of loop diuretics may be decreased by enalapril. Hydrochlorothiazide and furosemide have synergistic effects that may result in profound diuresis and serious electrolyte abnormalities. Monitor for dehydration and electrolyte abnormalities.

mTOR inhibitors (eg, everolimus, sirolimus)

Increased risk of angioedema, ranging from minor facial edema to life-threatening mouth and throat swelling, may occur.

Nondepolarizing muscle relaxants (eg, tubocurarine)

Possible increased responsiveness to the muscle relaxant due to diuretic-induced hypokalemia. If hypokalemia cannot be corrected, a lower dosage of nondepolarizing muscle relaxants may be needed.


Additive hypotensive effects and profound hypotension may occur. Start with lower doses of pergolide and monitor BP closely. If BP falls, dosage reduction may be needed.

Phenothiazines (eg, chlorpromazine)

May produce a synergistic hypotensive effect with postural syncope. Monitor BP (supine and standing) and adjust dosage of the antihypertensive as needed.

Potassium preparations (eg, potassium supplements, salt substitutes containing potassium), potassium-sparing diuretics (eg, spironolactone)

May increase serum potassium levels. Hyperkalemia, possibly with cardiac arrhythmias or arrest, may occur. Closely monitor serum potassium concentrations.

Pressor amines (eg, norepinephrine)

Response to pressor amines may be decreased. Use with caution.

Salicylates (aspirin, bismuth salicylate)

Hypotensive and vasodilator effects of enalapril may be decreased. Consider increasing the dosage of enalapril/hydrochlorothiazide or decreasing the salicylate dosage. A decreased dose of salicylates may avoid the interaction.


May cause severe hypotension. Use with caution and closely monitor BP.


The risk of phototoxicity may be increased if these agents are coadministered. Avoid coadministration.


May cause hyperkalemia and possibly cardiac arrhythmias. Closely monitor serum potassium.

Adverse Reactions


Orthostatic effects, orthostatic hypotension, other orthostatic effects (2%); palpitations, syncope, tachycardia (up to 2%); hypotension (1%).


Dizziness (9%); headache (6%); fatigue (4%); asthenia (2%); insomnia, nervousness, paresthesia, somnolence, vertigo (up to 2%).


Diaphoresis, pruritis, rash (up to 2%).


Nausea (3%); diarrhea (2%); abdominal pain, constipation, dry mouth, dyspepsia, flatulence, vomiting (up to 2%).


Impotence (2%); decreased libido, UTIs (up to 2%); increased BUN, increased serum creatinine (1%).


Decreased Hgb and Hct.


Elevated LFTs and/or serum bilirubin.


Gout (up to 2%); hypercalcemia; hyperglycemia; hyperkalemia; hypochloremic alkalosis; hypokalemia; hypomagnesemia; hyponatremia; increased triglyceride and cholesterol levels.


Muscle cramps (3%); arthralgia, back pain (up to 2%).


Cough (4%); dyspnea (up to 2%).


Chest pain, tinnitus (up to 2%); angioedema.



When pregnancy is detected, discontinue therapy as soon as possible. Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus.


Observe patients for signs of fluid or electrolyte imbalance (eg, hyponatremia, hypochloremic alkalosis, hypokalemia, hypercalcemia, hyperkalemia, hypomagnesemia). Periodically determine serum electrolytes at appropriate intervals. Monitor serum potassium levels at frequent intervals, especially during initial dosages, when dosages are changed, or with any illness that may influence renal function. Patients with mild renal impairment and diabetes should receive frequent and continued monitoring of serum electrolytes. Frequently monitor acid/base balance and serum electrolytes in severely ill patients in whom respiratory or metabolic acidosis may occur. Make periodic BUN and creatinine determinations, especially in elderly patients and patients with confirmed or suspected hepatic or renal insufficiencies. Monitor blood glucose in diabetic patients when therapy is started or dose is changed. Consider periodic monitoring of WBC in patients with collagen vascular disease and renal disease.


Category D . Use of drugs that act on the renin-angiotensin system during the second and third trimesters reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. Do not use during pregnancy. Thiazides cross the placenta and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.


Excreted in breast milk. Breast-feeding is not recommended.


Safety and efficacy not established.


Hydrochlorothiazide is excreted by the kidneys; the risk of toxic reactions may be greater in patients with renal impairment.


Anaphylactoid reactions have been reported. Sensitivity reactions may occur.

Renal Function

Not recommended in patients with severe renal disease (CrCl 30 mL/min or less); thiazides may precipitate azotemia. Cumulative drug effects may occur.

Hepatic Function

Use with caution in patients with impaired hepatic function or progressive liver disease because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.


Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with enalapril. This may occur at any time during treatment. Intestinal angioedema has also been reported with ACE inhibitors. Black patients have a higher incidence of angioedema compared with nonblack patients.

Aortic stenosis/hypertrophic cardiomyopathy

Use with caution in patients with obstruction in the outflow tract of the left ventricle.


Persistent, nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy.

Electrolyte imbalance

Hyperkalemia, hypokalemia, hypercalcemia, hypochloremic alkalosis, hypomagnesemia, and/or hyponatremia may occur. Hyperkalemia is more likely to occur in patients with renal impairment or diabetes, or elderly or severely ill patients.

Hematologic effects

Agranulocytosis and bone marrow depression may occur.

Hepatic effects

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis, and (sometimes) death.


May occur, or acute gout may be precipitated.


Excessive hypotension may occur, especially in severely salt- or volume-depleted patients. Syncope has been reported.

Lipid effects

Increases in cholesterol and triglyceride levels may occur.

Ocular effects

Hydrochlorothiazide can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma within hours to weeks of drug initiation.


The antihypertensive effects of these drugs may be enhanced in the postsympathectomy patient.

Renal effects

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure, treatment with enalapril may be associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death. Increases in BUN and serum creatinine may occur.


In patients undergoing major surgery, or during anesthesia with agents that produce hypotension, enalapril may block angiotensin II formation secondary to compensatory renin release.

Systemic lupus erythematosus

May be activated or exacerbated.



Dehydration, dizziness, drowsiness, electrolyte abnormalities, hypotension, orthostatic hypotension, syncope.

Patient Information

  • Inform patients that angioedema, including laryngeal edema, may occur at any time during treatment. Advise patients to immediately report any signs or symptoms suggesting angioedema (eg, swelling of the face, extremities, eyes, lips, tongue; difficulty in swallowing or breathing) and to stop taking the medication until they have consulted their health care provider.
  • Caution patients to report light-headedness, especially during the first few days of therapy. If actual syncope occurs, advise patients to discontinue the medication until they have consulted their health care provider.
  • Caution all patients that excessive perspiration, dehydration, vomiting, or diarrhea may lead to an excessive fall in BP because of reduction in fluid volume.
  • Advise patients not to use salt substitutes containing potassium without consulting their health care provider.
  • Inform patients to promptly report any indication of infection (eg, sore throat, fever), which may be a sign of neutropenia.
  • Inform women of childbearing age about the consequences of exposure to enalapril/hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Advise women to report pregnancies to their health care provider as soon as possible.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.