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.