Ramipril

A to Z Drug Facts

 Action Competitively inhibits angiotensin I-converting enzyme, resulting in prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor. Clinical consequences include decrease in BP and indirect (by inhibiting aldosterone) decrease in sodium and fluid retention and increase in diuresis.

 Indications Treatment of hypertension; for stable patients who have demonstrated clinical signs of CHF within the first few days after sustaining acute MI. Reduce the risk of developing a major cardiovascular event in patients ³ 55 years of age because of a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that is accompanied by ³ 1 other cardiovascular risk factor (eg, hypertension, elevated total cholesterol levels, low HDL, cigarette smoking, documented microalbuminuria); reduce risk of MI, stroke, or death from cardiovascular causes.

 Contraindications Hypersensitivity to ACE inhibitors (particularly history of angioedema).

 Route/Dosage

Reduction in Risk of MI, Stroke, and Death from Cardiovascular Causes ADULTS: PO Initial dose: 2.5 mg qd/day for 1 wk, 5 mg qd/day for 3 wk, then increase the dose as tolerated to maintenance dose. Maintenance dose: 10 mg qd/day or in divided doses if patient is hypertensive or recently post-MI.

Hypertension

ADULTS: PO Initial dose: 2.5 mg qd initially. Maintenance dose: 2.5 to 20 mg/day as single dose or in 2 equally divided doses.

Patients with Renal Impairment

PO 1.25 mg qd in patients with creatinine clearance < 40 mL/min (serum creatinine > 2.5 mg/dL) (max 5 mg/day).

Heart Failure Post-MI

ADULTS: PO 2.5 mg bid. Switch to 1.25 mg bid if hypotension occurs. Titrate to target dose of 5 mg bid.

 Interactions

Allopurinol: Greater risk of hypersensitivity possible with coadministration. Antacids: Ramipril bioavailability may be decreased. Separate administration times by 1 to 2 hr. Capsaicin: May exacerbate cough. Digoxin: Increased digoxin levels. Indomethacin: May reduce hypotensive effects, especially in low-renin or volume-dependent hypertensive patients. Lithium: May cause increased lithium levels and symptoms of lithium toxicity. Loop diuretics: Effects of loop diuretics may be decreased. Phenothiazines: Enhanced hypotensive effects. Potassium supplements, potassium sparing diuretics: May cause increased potassium serum levels.

 Lab Test Interferences False elevation of liver enzymes, serum bilirubin, uric acid, and blood glucose may occur.

 Adverse Reactions

CV: Hypotension. CNS: Headache; dizziness; fatigue. DERM: Rash; pruritis. GI: Nausea; vomiting. HEMA: Decreases in Hgb or Hct; leukopenia; eosinophilia; proteinuria. META: Hyperkalemia. RESP: Angioneurotic edema with dyspnea; asthma; bronchospasm; upper respiratory infection; cough. OTHER: Asthenia, fever, hypersensitivity, flu-like syndrome, anaphylactoid reaction.

 Precautions

Pregnancy: Category D (second, third trimester); Category C (first trimester). Discontinue use in pregnant patients; fetal/neonatal injury and death have occurred. Closely observe infants with histories of in utero exposure. Lactation: Undetermined. Children: Safety and efficacy not established. Elderly patients: May show higher blood levels of active metabolite. Angioedema: Angioedema may occur. Use drug with extreme caution in patients with hereditary angioedema. Cough: Chronic cough may occur during treatment; it is more common in women. Hepatic impairment: Hepatic impairment use drug with caution. Dosage reduction may be required due to impaired metabolism. Hypotension/first-dose effect: Significant decreases in BP may occur following first dose, especially in severely salt- or volume-depleted patients (such as those receiving diuretics) or those with heart failure. Neutropenia and agranulocytosis: Neutropenia and agranulocytosis have occurred with similar agents; risk appears greater in presence of renal dysfunction, heart failure, or immunosuppression. Proteinuria: Proteinuria has occurred with agents in this class, especially with high doses or prior renal disease. Renal impairment: Dosage reduction is required in patients with renal impairment. May further decrease renal function with elevations in BUN and serum creatinine due to decreased renal perfusion.

 Administration/Storage

• Alternative route of administration: Ramipril capsules are usually swallowed whole. However, the capsules may be opened and the contents sprinkled on a small amount (» 4 oz) of applesauce or mixed in apple juice or water. Entire mixture should be consumed. Preprepared mixtures can be stored for up to 24 hr at room temperature or for up to 48 hr under refrigeration.
• Diuretics should be discontinued 2 to 3 days prior to ramipril therapy, if possible. If diuretic cannot be discontinued, dose reduction of ramipril is required.
• Observe for ³ 2 hr and until blood pressure has stabilized for at least an additional hour.
• Store at room temperature in tightly closed container.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies.
• Obtain baseline CBC, potassium level, and WBC counts and monitor at regular intervals.
• Obtain baseline orthostatic BP prior to first dose. Monitor at frequent intervals during first 2 wk of therapy.
• Obtain baseline renal and liver function tests. Monitor renal function test results at regular intervals during drug therapy, especially in patients with renal impairment.
• Note that patients with severe CHF may experience renal failure during ACE inhibitor therapy.
• Assess for proteinuria at monthly intervals.
• Notify healthcare provider if patient develops hypotension, nausea, vomiting, headache, dizziness, fatigue, angioedema, fever, infection or mouth sores.

 Patient/Family Education

• Advise patient that chronic dry cough may develop and to notify their healthcare provider if cough becomes bothersome.
• Instruct patient to maintain adequate fluid status and to avoid excess dehydration, perspiration, or overhydration.
• Advise patient to consult their healthcare provider prior to using salt substitutes containing potassium.
• Instruct patient to notify their healthcare provider of persistent rash, angioedema, abdominal pain, jaundice, excessive fatigue, irregular heart rate, or chest pain.
• Teach family member or friend how to take BP and instruct patient to keep written record.
• Encourage patient to follow nonmedical interventions to control hypertension: weight control, sodium and alcohol restriction, smoking cessation, and regular exercise.
• Instruct patient not to take otc medications without first consulting with their healthcare provider.
• Advise patient to avoid sudden position changes to prevent orthostatic hypotension; a hot bath or shower may aggravate dizziness.
• Tell patient to avoid abrupt discontinuation of therapy unless instructed by their healthcare provider.
• Inform patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts