ramipril

REMS

Alone or with other agents in the management of hypertension.
Reduction of risk of myocardial infarction, stroke, or death from cardiovascular causes in patients at least 55 years of age who are at high risk of developing a major cardiovascular event because of a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that is accompanied by at least one other cardiovascular risk factor.
Reduction of risk of death, heart-failure–related hospitalizations, and progression of heart failure in patients with signs of heart failure following myocardial infarction.

Action ⬆ ⬇

Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors also prevent the degradation of bradykinin and other vasodilatory prostaglandins. ACE inhibitors also ↑ plasma renin levels and ↓ aldosterone levels. Net result is systemic vasodilation.

Therapeutic effects:

Lowering of BP in hypertensive patients.
Decreased risk of myocardial infarction, stroke, or death from cardiovascular causes in high-risk patients.
Increased survival and decreased heart failure progression after myocardial infarction.

Pharmacokinetics ⬆ ⬇

Absorption: 50–60% absorbed following oral administration.

Distribution: Crosses the placenta; may enter breast milk.

Metabolism/Excretion: Converted by the liver to ramiprilat, the active metabolite; 60% excreted in urine; 40% in feces.

Half-Life: Ramiprilat:13–17 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

(effect on BP—single dose‡)

ROUTE	ONSET	PEAK	DURATION
PO	within 1–2 hr	3–6 hr	24 hr

‡Full effects may not be noted for several wk.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
History of angioedema with previous use of ACE inhibitors;
Concurrent use with aliskiren in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min);
Concurrent use with sacubitril;
OB: Can cause injury or death of fetus—if pregnancy occurs, discontinue immediately;
Lactation: Discontinue drug or use formula.

Use Cautiously in:

Black patients (monotherapy for hypertension less effective, may require additional therapy; higher risk of angioedema);
Surgery/anesthesia (hypotension may be exaggerated);
Women of childbearing potential;
Renal impairment (especially renal artery stenosis), hypovolemia, hyponatremia, concurrent diuretic therapy–initial dose ↓ recommended;
Pedi: Safety not established;
Geri: Initial dose ↓ recommended.

Exercise Extreme Caution in:

Family history of angioedema.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, chest pain

Derm: rashes

F and E: hyperkalemia

GI: diarrhea, nausea, vomiting

GU: impaired renal function

Neuro: dizziness, fatigue, headache, vertigo, weakness

Resp: cough

Misc: ANGIOEDEMA

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with sacubitril may ↑ risk of angioedema and is contraindicated; do not administer within 36 hr of switching to/from sacubitril/valsartan.
Excessive hypotension may occur with concurrent use of diuretics.
Additive hypotension with other antihypertensive agents.
↑risk of hyperkalemia with concurrent use of potassium supplements,potassium-sparing diuretics, or potassium-containing salt substitutes.
↑risk of hyperkalemia, renal dysfunction, hypotension, and syncope with concurrent use of angiotensin II receptor blockers or aliskiren; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/min; avoid concurrent use with angiotensin II receptor blockers
NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.
↑levels and may ↑ the risk of lithium toxicity.
↑risk of angioedema with temsirolimus, sirolimus, or everolimus.

Route/Dosage ⬆ ⬇

Hypertension

PO (Adults ): 2.5 mg once daily, slowly may be ↑ up to 20 mg/day in 1–2 divided doses (initiate therapy at 1.25 mg/day in patients receiving diuretics).

Heart Failure Post-Myocardial Infarction

PO (Adults ): 1.25–2.5 mg twice daily initially, may be ↑ slowly up to 5 mg twice daily.

Reduction in Risk of MI, Stroke, and Death from Cardiovascular Causes

PO (Adults ): 2.5 mg once daily for 1 wk, then 5 mg once daily for 3 wk, then ↑ as tolerated to 10 mg once daily (can also be given in 2 divided doses).

Renal Impairment

PO (Adults ): CCr <40 mL/min: Initiate therapy at 1.25 mg once daily, may be slowly titrated up to 5 mg/day in 1–2 divided doses.

Availability ⬆ ⬇

(Generic available)

Capsules: 1.25 mg; 2.5 mg; 5 mg; 10 mg; 15 mg
Tablets: 1.25 mg; 2.5 mg; 5 mg; 10 mg

Assessment ⬆ ⬇

Hypertension: Monitor BP and pulse frequently during initial dose adjustment and periodically during therapy. Notify health care professional of significant changes.
- Monitor frequency of prescription refills to determine compliance.
- Assess patient for signs of angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing); may occur at any time during therapy. Discontinue medication and provide supportive care.
Heart Failure: Monitor weight and assess patient routinely for resolution of fluid overload (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).

Lab Test Considerations:

Monitor BUN, creatinine, and electrolyte levels periodically. Serum potassium, BUN and creatinine may be ↑, whereas sodium levels may be ↓. If ↑ BUN or serum creatinine concentrations occur, dose reduction or withdrawal may be required.
- May cause hyperkalemia.
- Monitor CBC periodically during therapy in patients with collagen vascular disease and/or renal disease. May rarely cause ↓ in hemoglobin and hematocrit as well as neutropenia and eosinophilia.
- May cause ↑ AST, ALT, alkaline phosphatase, serum bilirubin, uric acid, and glucose.

Implementation ⬆ ⬇

Correct volume depletion, if possible, before initiation of therapy. Precipitous drop in BP during first 1–3 hr following first dose may require volume expansion with normal saline. Discontinuing diuretic therapy or cautiously increasing salt intake 2–3 days prior to initiation may decrease risk. Monitor closely for at least 1 hr after BP has stabilized. Resume diuretics if BP is not controlled.
PO: Capsules may be opened and sprinkled on applesauce, or dissolved in 4 oz water or apple juice for patients with difficulty swallowing. Effectiveness is same as capsule. Pre-prepared mixtures can be stored for up to 24 hr at room temperature or up to 48 hr if refrigerated.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of continuing to take medication as directed at the same time each day, even if feeling well. Take missed doses as soon as remembered but not if almost time for next dose. Do not double doses. Warn patient not to discontinue ACE inhibitor therapy unless directed by health care professional.
- Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care professional (see Food Sources for Specific Nutrients).
- Caution patient to change positions slowly to minimize orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may increase orthostatic hypotension.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications especially NSAIDs and cough, cold, or allergy medications.
- May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
- Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
- Instruct patient to notify health care professional immediately if rash; mouth sores; sore throat; fever; swelling of hands or feet; irregular heartbeat; chest pain; dry cough; hoarseness; swelling of face, eyes, lips, or tongue; or if difficulty swallowing or breathing occurs. Persistent dry cough may occur and may not subside until medication is discontinued. Consult health care professional if cough becomes bothersome. Also notify health care professional if nausea, vomiting, or diarrhea occurs and continues.
- Advise women of childbearing age to use contraception and notify health care professional if pregnancy is planned or suspected or if breastfeeding. If pregnancy is detected, discontinue medication as soon as possible.
- Emphasize the importance of follow-up examinations to evaluate effectiveness of medication.
Hypertension: Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, discontinuation of smoking, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
- Instruct patient and family on correct technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes to health care professional.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇