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Ramipril

Pronunciation

Pronunciation: ruh-MIH-prill
Class: Angiotensin converting enzyme (ACE) inhibitor

Trade Names

Altace
- Capsules 1.25 mg
- Capsules 2.5 mg
- Capsules 5 mg
- Capsules 10 mg

Apo-Ramipril (Canada)
Novo-Ramipril (Canada)
ratio-Ramipril (Canada)

Pharmacology

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.

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Pharmacokinetics

Absorption

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).

Distribution

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.

Metabolism

In liver to active metabolite ramiprilat, which had 6 times the ACE inhibitory activity.

Elimination

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 Populations

Renal 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.

Contraindications

Hypersensitivity to ACE inhibitors (particularly history of angioedema).

Dosage and Administration

Heart Failure Post-MI
Adults

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
Adults

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
Adults

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.

Storage/Stability

Store tablets at controlled room temperature (59° to 89°F). Protect from moisture.

Drug Interactions

Antacids

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.

Adverse Reactions

Cardiovascular

Hypotension (11%); angina pectoris (3%); postural hypotension, syncope (2%).

CNS

Dizziness (4%).

EENT

Vertigo (2%).

GI

Nausea, vomiting (2%); diarrhea (1%).

Genitourinary

Abnormal renal function (1%).

Hematologic

Neutropenia, agranulocytosis.

Metabolic

Hyperkalemia (1%).

Respiratory

Cough (8%).

Miscellaneous

Angioedema (0.3%); anaphylactoid reactions.

Precautions

Warnings

Pregnancy

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.


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

May show higher blood levels of active metabolite.

Renal Function

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.

Hepatic Function

Use drug with caution. Dosage reduction may be required because of impaired metabolism.

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 failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

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.

Overdosage

Symptoms

Hypotension.

Patient Information

  • 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.

Copyright © 2009 Wolters Kluwer Health.

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