Enalapril + Hydrochlorothiazide

Indications

Hypertension, Heart Failure

Adult Dose

Oral Hypertension Adult: 10-40 mg/12.5-50 mg (enalapril/HCTZ)/day PO qDay or divided q12hr Chronic heart failure Adult: Enalapril maleate-10mg+ Hydrochlorothiazide-25mg (tablets) 1/2-1 tab daily. Elderly: Cautious use

Renal Dose

Renal Impairment Severe (CrCl <30 mL/min) : Not recommended; use loop diuretic instead CrCl >30 mL/min: No dose adjustment necessary

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity to ACE inhibitors, thiazides or sulfonamides ACE-inibitor induced angioedema, hereditary or idiopathic angioedema Pregnancy (2nd and 3rd trimesters): significant risk of fetal/neonatal morbidity and mortality (due to enalapril) Renal stenosis or anuria Do not coadminister with aliskiren in patients with diabetes

Precautions

Begin combination therapy only after failed monotherapy Severe renal impairment, hepatic impairment Risk of hypotension, especially in CHF patients Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors If laryngeal stridor or angioedema of the face, tongue, or glottis occurs discontinue therapy and institute appropriate therapy immediately Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors Cholestatic jaundice may occur, which may progress to fulminant hepatic necrosis; discontinue Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation Hyperkalemia may occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium sparing diuretics and potassium supplements; use cautiously if at all with these agents Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia Hydrochlorothiazide may precipitate gout in patients with familial predisposition to gout or chronic renal failure Symptomatic hypotension with or without syncope can occur with Ace inhibitors; mostly observed in volume depleted patients, correct volume depletion prior to initiation; monitor closely when initiating and increasing dosing Agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia reported with other ACE inhibitor; patients with renal impairment are at high risk; monitor CBC

Pregnancy-Lactation

C Pregnancy Category: C (1st trimester); D (2nd and 3rd trimesters) Lactation: Enters breast milk/not recommended

Interactions

Significant increase in serum K levels with K supplements and K sparing diuretics. Lithium toxicity in patients receiving lithium concomitantly. Alcohol, barbiturates, narcotics potentiate orthostatic hypotension. Dosage adjustment of antidiabetic drugs needed. Potentiation of action of other antihypertensives, corticosteroids, ACTH.

Adverse Effects

1-10% Enalapril Dizziness (4-8%),Hypotension (0.9-6.7%),Headache (2-5%),Chest pain (2%),Cough (1-2%),Rash (1.5%) Hydrochlorothiazide Hypotension,Anorexia,Epigastric distress,Hypokalemia,Phototoxicity

Mechanism of Action

Enalapril is an ACE inhibitor, which reduces the levels of AT II and aldosterone. This action is potentiated by Na depletion which activates the renin-angiotensin-aldosterone system. Hydrochlorothiazide also eliminates the vol factor commonly occuring with long term use of vasodilators.

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