Enalapril

Pronunciation

Enalapril 10mg

Enalapril 5mg

Generic Name:	Enalapril
Class:	Cardiovascular Drug
Subclass:	ACE inhibitors
Legal Classification:	P1S1S3

Drug Names

Generic Name 藥物化學名稱	HA Code 藥物代碼	Legal Classification法律藥物分類
Enalapril Maleate Tablet 2.5mg		P1S1S3
Enalapril Maleate Tablet 5mg	ENAL02	P1S1S3
Enalapril Maleate Tablet 10mg	ENAL03	P1S1S3
Enalapril Maleate Tablet 20mg	ENAL01	P1S1S3

Mechanism of Action

Enalapril is an inhibitor of angiotensin-I converting enzyme (ACE inhibitor). The beneficial effects of ACE inhibitors appear to result primarily from the suppression of the plasma renin-angiotensin-aldosterone system. Renin is synthesized by the kidneys and released into the circulation where it converts angiotensinogen to angiotensin-I. Angiotensin-I is then converted by angiotensin converting enzyme to angiotensin-II. Angiotensin-II is a potent vasoconstrictor responsible for arterial vasoconstriction and increased blood pressure, as well as for stimulation of the adrenal gland to secrete aldosterone. Inhibition of ACE results in decreased plasma angiotensin-II, which leads to decreased vasopressor activity and to reduced aldosterone secretion. Enalapril is used in the treatment of hypertension and heart failure. It may also be given prophylactically to patients with asymptomatic left ventricular dysfunction to delay the onset of symptomatic heart failure, and has been used in patients with left ventricular dysfunction to reduce the incidence of coronary ischaemic events, including myocardial infarction.

Route of Administration

Enalapril is administered orally as enalapril maleate.

Dosage

Hypertension

• Adult: initially 5 mg once daily, lower initial doses may be required when used in addition to diuretic or in renal impairment; maintenance 20 mg once daily; maximum 40 mg/day.

Heart failure

• Adult: initially 2.5 mg once daily, increased if tolerated to 10-20 mg twice daily, doses to be increased gradually over 2-4 weeks

Onset of antihypertensive activity was usually seen at 1 hour, with peak reduction of blood pressure achieved by 4 to 6 hours after administration.

The duration of effect is dose related. However, at recommended doses, antihypertensive and haemodynamic effects have been shown to be maintained for at least 24 hours.

Side Effects

System Organ Class	Frequency	Adverse reactions
Nervous system disorders	Common	Dizziness, headache, taste alteration
Psychiatric disorders	Common	depression
	Uncommon	Confusion, insomnia
Respiratory disorders	Common	Dry, irritating (non-productive) cough and dyspnoea
Eye disorders	Common	Blurred vision
Skin disorders	Common	Rash Oedema of the face, extremeties, lips, tongue, glottis and/or larynx
Gastro-intestinal disorders	Common	Abdominal pain, nausea, , diarrhoea
	Uncommon	Constipation, anorexia, peptic ulcer
	Rare	Stomatitis, small bowel angioedema
	Very rare	Glossitis, pancreatitis
Cardiac disorders	common	Chest pain, arrhythmia, tachycardia
Vascular disorder	common	Hypotension
	Uncommon	flushing
	Rare	Raynaud’s syndrome

Pharmacokinetics

Oral Enalapril is rapidly absorbed, with peak serum concentrations of enalapril occurring within 1 hour.

Following absorption, oral enalapril is rapidly and extensively hydrolysed to enalaprilat, a potent angiotensin converting enzyme inhibitor. Peak serum concentrations of enalaprilat occur 3 to 4 hours after an oral dose of enalapril.

The effective half-life for accumulation of enalaprilat following multiple doses of enalapril is 11 hours. In patients with normal renal function, steady state serum concentrations of enalaprilat were achieved by the fourth day of treatment.

Drug Management

Safety: For hypertension the first dose should preferably be given at bedtime.

PREGNANCY should be avoided in pregnancy unless essential.

BREAST FEEDING avoid in the few weeks after delivery, particularly in preterm infants – risk of profound neonatal hypotension; can be used in mothers breast-feeding older infants if essential.

HEPATIC IMPAIRMENT Enalapril is a prodrug and requires close monitoring in patients with hepatic impairment.

RENAL IMPAIRMENT Max. initial dose 2.5 mg daily if eGFR < 30ml/minute/1.73 m2

MONITORING REQUIREMENTS Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and monitored during treatment (more frequently if side effects mentioned are present).

Diuretics: prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with enalapril.

Potassium sparing diuretics (triamterene, amiloride and spironolactone) or potassium supplement: may cause significant increase in serum potassium.

Caution:

• Concomitant diuretics – first dose hypotension (especially in patients taking high doses of diuretics, on a low-sodium diet, on dialysis, dehydrated , or with heart failure)
• Use with care in those with a history of angioedema
• Use with care in patients with severe or symptomatic aortic stenosis (risk of hypotension)