Class: Angiotensin converting enzyme (ACE) inhibitor
- Capsules 1.25 mg
- Capsules 2.5 mg
- Capsules 5 mg
- Capsules 10 mg
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.
Extent of absorption in GI tract is at least 50% to 60%. T max is 1 h (parent compound) or 2 to 4 h (metabolite, ramiprilat). Bioavailability is 28% (ramipril) or 44% (ramiprilat).
Protein binding is about 73% (parent) or about 56% (metabolite). Plasma concentrations of ramiprilat decline in a triphasic manner: initial rapid decline (representing distribution into peripheral compartment), apparent elimination phase, and terminal elimination phase.
In liver to active metabolite ramiprilat, which had 6 times the ACE inhibitory activity.
Eliminated in urine (60% of parent and metabolites) and feces (40%). Less than 2% of drug recovered in urine is unchanged. The t ½ is less than 50 h (ramiprilat).
Special PopulationsRenal Function Impairment
In patients with Ccr less than 40 mL/min, peak levels of metabolite approximately doubled. AUC was 3 to 4 times larger. Urinary excretion of metabolite is reduced. Higher peak and trough ramiprilat levels.Hepatic Function Impairment
Slowed metabolism of ramiprilat. Ramipril plasma levels increase about 3-fold.
Indications and Usage
Treatment of hypertension; for stable patients who have demonstrated clinical signs of CHF within the first few days after sustaining acute MI; reduce risk of MI, stroke, or death from CV causes in patients at high risk.
Hypersensitivity to ACE inhibitors (particularly history of angioedema).
Dosage and AdministrationHeart Failure Post-MI
PO 2.5 mg twice daily. Switch to 1.25 mg twice daily if hypotension occurs. Titrate to target dose of 5 mg twice daily.Hypertension
PO Initial dose is 2.5 mg every day initially. Maintenance dose is 2.5 to 20 mg/day as single dose or in 2 equally divided doses.Patients with Renal Impairment
PO 1.25 mg every day in patients with Ccr below 40 mL/min (serum creatinine higher than 2.5 mg/dL; max, 5 mg/day).Reduction in Risk of MI, Stroke, and Death from CV Causes
PO Initial dose is 2.5 mg every day for 1 wk, 5 mg every day for 3 wk, then increase the dose as tolerated to maintenance dose. Maintenance dose is 10 mg every day or in divided doses if patient is hypertensive or recently post-MI.
Store tablets at controlled room temperature (59° to 89°F). Protect from moisture.
Ramipril bioavailability may be decreased. Separate administration times by 1 to 2 h.Capsaicin
May exacerbate cough.Digoxin
Increased or decreased digoxin levels.Diuretics
Increased risk of hypotension.Indomethacin, salicylates (eg, aspirin)
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.
Laboratory Test Interactions
False elevation of liver enzymes, serum bilirubin, uric acid, and blood glucose may occur.
Hypotension (11%); angina pectoris (3%); postural hypotension, syncope (2%).
Nausea, vomiting (2%); diarrhea (1%).
Abnormal renal function (1%).
Angioedema (0.3%); anaphylactoid reactions.
When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.
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.
Safety and efficacy not established.
May show higher blood levels of active metabolite.
Dosage reduction is required in patients with renal function impairment. May further decrease renal function with elevations in BUN and serum creatinine caused by decreased renal perfusion.
Use drug with caution. Dosage reduction may be required because of impaired metabolism.
Angioedema may occur. Use drug with extreme caution in patients with hereditary angioedema.
Chronic cough may occur during treatment; it is more common in women.
Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.
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 has occurred with agents in this class, especially with high doses or prior renal disease.
- Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
- Advise patient to try to take each dose at about the same time each day.
- Inform hypertensive patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
- Caution patient not to change the dose or stop taking unless advised by health care provider.
- Instruct patient to continue taking other medications for condition as prescribed by health care provider.
- Instruct patient in BP and pulse measurement skills.
- Advise patient to monitor and record BP and pulse at home and to inform health care provider should abnormal measurements be noted. Also advise patient to take record of BP and pulse to each follow-up visit.
- Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
- Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
- Emphasize to hypertensive patient the importance of the following other modalities on BP control: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
- Emphasize to heart failure patient the importance of the following other modalities that can help control heart failure symptoms: weight control, progressive exercise program, smoking cessation, and moderate intake of alcohol and salt.
- Advise heart failure patient to weigh daily, keep a record of daily weights, and notify health care provider if rapid weight gain (eg, 5 pounds in 1 wk) is noted or if edema or shortness of breath are getting worse.
- Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in lightheadedness or fainting.
- Advise patient that medication may cause dizziness or lightheadedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
- Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
- Instruct patient to stop taking drug and immediately report any of the following symptoms to health care provider: sore throat, fever, swelling of the hands or feet, irregular heartbeat, chest pains, fainting, swelling of the face, lips, eyelids, or tongue, difficulty breathing.
- Instruct patient to inform health care provider if a persistent cough develops while taking this medication.
- Caution patient not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by health care provider.
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