Ramipril

Ramipril capsules are an angiotensin converting enzyme (ACE) inhibitor indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. It may be used alone or in combination with thiazide diuretics. In patients 55 years or older at high risk of developing a major cardiovascular event, ramipril capsules are indicated to reduce the risk of myocardial infarction, stroke, or death from cardiovascular causes. Ramipril capsules are indicated in stable patients who have demonstrated clinical signs of congestive heart failure post-myocardial infarction.

Ramipril and ramiprilat inhibit ACE in human subjects and animals. Angiotensin converting enzyme is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. In hypertensive patients with normal renal function treated with ramipril alone for up to 56 weeks, approximately 4% of patients during the trial had an abnormally high serum potassium and an increase from baseline greater than 0.75 mEq/L, and none of the patients had an abnormally low potassium and a decrease from baseline greater than 0.75 mEq/L.

Hypertension: Initial dose is 2.5 mg to 20 mg once daily. Adjust dosage according to blood pressure response after 2 to 4 weeks of treatment. The usual maintenance dose following titration is 2.5 mg to 20 mg daily as a single dose or equally divided doses. Reduction in the risk of myocardial infarction, stroke, or death from cardiovascular causes: 2.5 mg once daily for 1 week, 5 mg once daily for 3 weeks, and increased as tolerated to a maintenance dose of 10 mg once daily. Heart failure post-myocardial infarction: Starting dose of 2.5 mg twice daily. If patient becomes hypotensive at this dose, decrease dosage to 1.25 mg twice daily. Increase dose as tolerated toward a target dose of 5 mg twice daily, with dosage increases about 3 weeks apart. Dosage adjustment: See respective sections pertaining to dosage adjustment in special situations.

Ramipril capsules are contraindicated in patients who are hypersensitive to this product or any other ACE inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor). Ramipril capsules are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer ramipril capsules within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor. Do not co-administer ramipril capsules with aliskiren: in patients with diabetes Angioedema related to previous treatment with an ACE inhibitor, or a history of hereditary or idiopathic angioedema.

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue ramipril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Angioedema, increased risk in patients with a prior history. Hypotension and hyperkalemia. Renal impairment: monitor renal function during therapy. Avoid concomitant use of an ACE inhibitor and angiotensin blocker. Rare cholestatic jaundice and hepatic failure. Rare neutropenia and agranulocytosis

The most common adverse reactions in patients with hypertension included headache, dizziness, fatigue, and cough.

Diuretics: Possibility of excessive hypotension. Lithium: Use with caution. Gold: Nitritoid reactions have been reported. NSAIDs use may lead to increased risk of renal impairment and loss of antihypertensive effect. mTOR inhibitor or neprilysin inhibitor use may increase angioedema risk.

Store at 20° to 25°C (68° to 77°F).