Ramipril

Ramipril is used alone or in combination with other medications to treat high blood pressure. It is also used to reduce the risk of heart attack and stroke in patients at risk for these problems and to improve survival in patients with heart failure after a heart attack. Ramipril is in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten the blood vessels, so blood flows more smoothly and the heart can pump blood more efficiently.

High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Ramipril is a prescription medication used:

• to treat high blood pressure
• to treat heart failure after a heart attack
• to lower the risk of heart attacks, stroke, and death from cardiovascular (heart or blood vessel) causes

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• aliskiren (Tekturna; also in Amturnide, Tekamlo, Tekturna HCT)
• angiotensin receptor blockers such as candesartan (Atacand), losartan (Cozaar), and telmisartan (Micardis, Twynsta)
• nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen (Naprosyn), ibuprofen (Motrin, Advil), and indomethacin (Indocin)
• diuretics such as hydrochlorothiazide or chlorthalidone
• vasodilators such as nitroglycerin (Nitrostat), hydralazine, and minoxidil (Loniten)
• potassium-sparing diuretic such as spironolactone (Aldactone), triamterene (Dyrenium), and amiloride (Midamor)
• lithium (Eskalith, Lithobid)

This is not a complete list of ramipril drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with ramipril including:

• Angioedema (a serious hypersensitivy reaction). Tell your healthcare profession right away if you have signs or symptoms of angioedema, which include:
  • swelling of face, eyes, lips, tongue, larynx and extremities
  • difficulty in swallowing or breathing
  • hoarseness (having difficulty making sounds when trying to speak)
• Hyperkalemia (high levels of potassium in the blood). This medication may lead to increased levels of potassium, which could lead to side effects such as heart arrhythmias (irregular heartbeat) and nausea.
• Hypotension (low blood pressure). Excessive perspiration and dehydration may lead to an excessive fall in blood pressure (hypotension). Vomiting or diarrhea may also lead to a fall in blood pressure.
• Decline in kidney function. Your doctor may need to perform tests to determine the stability of the function of your kidneys, especially in patients who already have kidney dysfunction. This risk is also present when combined with angiotensin receptor blockers (ARBs) or aliskiren.
• Neutropenia (rare). Report any sign of infection such as sore throat or fever, which may be a sign of neutropenia (a decreased amount of white blood cells).
• Liver failure (rare). Report any signs or symptoms of hepatic failure, including:
  • yellowing of the skin or eyes
  • nausea
  • vomiting
  • fatigue
  • itching

Do not take ramipril if you:

• have a history of angioedema related to previous treatment with an ACE inhibitor, or a history of angioedema altogether
• are allergic to ramipril or any of this medication's ingredients

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of ramipril, salt substitutes containing potassium should be avoided.

• Take ramipril exactly as prescribed.
• Ramipril comes in capsule form and is given once or twice a day, with or without food.
• The ramipril capsule can also be opened and its contents sprinkled on a small amount (about 4 oz.) of applesauce or mixed in 4 oz. (120 mL) of water or apple juice. To be sure that ramipril is not lost when such a mixture is made, consume the entire mixture. The mixtures can also be prepared and stored for up to 24 hours at room temperature or up to 48 hours under refrigeration.
• If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of ramipril at the same time.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Hypertension

Ramipril capsules, USP are 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. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Ramipril capsules, USP may be used alone or in combination with thiazide diuretics.

Heart Failure Post-Myocardial Infarction

Ramipril capsules, USP are indicated in stable patients who have demonstrated clinical signs of congestive heart failure within the first few days after sustaining acute myocardial infarction. Administration of Ramipril capsules to such patients has been shown to decrease the risk of death (principally cardiovascular death) and to decrease the risks of failure-related hospitalization and progression to severe/resistant heart failure [see CLINICAL STUDIES (14.3)].

Pregnancy

Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Ramipril as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Ramipril unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Ramipril for hypotension, oliguria, and hyperkalemia [see USE IN SPECIFIC POPULATIONS (8.4)].

Nursing Mothers

Ingestion of a single 10 mg oral dose of Ramipril resulted in undetectable amounts of Ramipril and its metabolites in breastmilk. However, because multiple doses may produce low milk concentrations that are not predictable from a single dose, do not use Ramipril in nursing mothers.

Pediatric Use

Neonates with a history of in utero exposure to Ramipril:

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Ramipril, which crosses the placenta, can be removed from the neonatal circulation by these means, but limited experience has not shown that such removal is central to the treatment of these infants.

Safety and effectiveness in pediatric patients have not been established. Irreversible kidney damage has been observed in very young rats given a single dose of Ramipril.

Geriatric Use

Of the total number of patients who received Ramipril in U.S. clinical studies of Ramipril, 11% were ≥ 65 years of age while 0.2% were ≥ 75 years of age. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

One pharmacokinetic study conducted in hospitalized elderly patients indicated that peak Ramiprilat levels and area under the plasma concentration-time curve (AUC) for Ramiprilat are higher in older patients.

Renal Impairment

A single-dose pharmacokinetic study was conducted in hypertensive patients with varying degrees of renal impairment who received a single 10 mg dose of Ramipril. Patients were stratified into four groups based on initial estimates of creatinine clearance: normal (> 80 mL/min), mild impairment (40 to 80 mL/min), moderate impairment (15 to 40 mL/min), and severe impairment (< 15 mL/min). On average, the AUC0-24h for Ramiprilat was approximately 1.7-fold higher, 3.0-fold higher, and 3.2-fold higher in the groups with mild, moderate, and severe renal impairment, respectively, compared to the group with normal renal function. Overall, the results suggest that the starting dose of Ramipril should be adjusted downward in patients with moderate-to-severe renal impairment.

Ramipril is a 2-aza-bicyclo [3.3.0]-octane-3-carboxylic acid derivative. Ramipril, USP is a white to almost white crystalline powder. It is freely soluble in methanol and sparingly soluble in water. Ramipril melts between 105°C and 112° C.

Ramipril’s chemical name is (2S, 3aS, 6aS)-1[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl] octahydrocyclopenta [b]pyrrole-2-carboxylic acid, 1 -ethyl ester; its structural formula is:

Its molecular formula is C23H32N2O5, and its molecular weight is 416.5.

Ramiprilat, the diacid metabolite of Ramipril, is a non-sulfhydryl angiotensin converting enzyme inhibitor. Ramipril is converted to Ramiprilat by hepatic cleavage of the ester group.

Each Ramipril capsule, USP intended for oral administration contains 1.25 mg or 2.5 mg or 5 mg or 10 mg of Ramipril, USP. In addition, each capsule contains the following inactive ingredients: gelatin, pregelatinized starch and titanium dioxide. Additionally each 1.25 mg capsule shell contains: FD&C red # 40, FD&C yellow # 5 and FD&C yellow # 6, 2.5 mg capsule shell contains: D&C yellow # 10 and FD&C red # 40, 5 mg capsule shell contains: FD&C blue # 1, FD&C red # 40 and FD&C yellow # 6 and 10 mg capsule shell contains:, D&C red # 28, D&C yellow # 10 and FD&C blue # 1. The capsule is printed with black pharmaceutical ink which contains black iron oxide as a coloring agent.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of a tumorigenic effect was found when Ramipril was given by gavage to rats for up to 24 months at doses of up to 500 mg/kg/day or to mice for up to 18 months at doses of up to 1000 mg/kg/day. (For either species, these doses are about 200 times the maximum recommended human dose when compared on the basis of body surface area.) No mutagenic activity was detected in the Ames test in bacteria, the micronucleus test in mice, unscheduled DNA synthesis in a human cell line, or a forward gene-mutation assay in a Chinese hamster ovary cell line. Several metabolites and degradation products of Ramipril were also negative in the Ames test. A study in rats with dosages as great as 500 mg/kg/day did not produce adverse effects on fertility.

No teratogenic effects of Ramipril were seen in studies of pregnant rats, rabbits, and cynomolgus monkeys. On a body surface area basis, the doses used were up to approximately 400 times (in rats and monkeys) and 2 times (in rabbits) the recommended human dose.

• Altace

Ramipril is an ACE inhibitor which prevents the formation of angiotensin II from angiotensin I and exhibits pharmacologic effects that are similar to captopril. Ramipril must undergo enzymatic saponification by esterases in the liver to its biologically active metabolite, ramiprilat. The pharmacodynamic effects of ramipril result from the high-affinity, competitive, reversible binding of ramiprilat to angiotensin-converting enzyme, thus preventing the formation of the potent vasoconstrictor angiotensin II. This isomerized enzyme-inhibitor complex has a slow rate of dissociation, which results in high potency and a long duration of action; a CNS mechanism may also be involved in the hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure

Absorption

Well absorbed (50% to 60%)

Distribution

Plasma levels decline in a triphasic fashion; rapid decline is a distribution phase to peripheral compartment, plasma protein and tissue ACE (half-life: 2-4 hours); second phase is an apparent elimination phase representing the clearance of free ramiprilat (half-life: 9-18 hours); and final phase is the terminal elimination phase representing the equilibrium phase between tissue binding and dissociation

Metabolism

Hepatic to the active form, ramiprilat

Excretion

Urine (60%) and feces (40%) as parent drug and metabolites

Slowed metabolism of ramiprilat. Ramipril plasma levels increase about 3-fold.

Heart failure post-myocardial infarction: Treatment of heart failure (HF) after myocardial infarction (MI).

Hypertension: Management of hypertension (monotherapy or in combination with thiazide diuretics).

Reduction in risk of MI, stroke, and death from cardiovascular causes: To reduce the risk of MI, stroke, and death in patients ≥55 years at high risk of developing major cardiovascular events.

Guideline recommendations:

Heart failure: The 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure guidelines recommend the use of ACE inhibitors, along with other guideline-directed medical therapies, to prevent HF in patients with a reduced ejection fraction who have a history of MI (stage B HF), to prevent HF in any patient with a reduced ejection fraction (stage B HF), or to treat those with HF and reduced ejection fraction (stage C HFrEF) (Yancy 2013)

Hypertension: The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients:

• Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg.

• Patients <60 years of age with SBP ≥140 mm Hg or DBP is ≥90 mm Hg.

• Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg.

• Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg.

Coronary artery disease (CAD) and hypertension: The American Heart Association, American College of Cardiology and American Society of Hypertension (AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in patients with CAD recommends the use of an ACE inhibitor (or an ARB) as part of a regimen in patients with hypertension and chronic stable angina if there is prior MI, LV systolic dysfunction, diabetes mellitus, or CKD. A BP target of <140/90 mm Hg is reasonable for the secondary prevention of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines recommend an ACE inhibitor (or an ARB) for patients with HTN and diabetes with albuminuria (urinary albumin-to-creatinine ratio [UACR] ≥30 mg/g). For patients with hypertension and diabetes without albuminuria, any of the 4 classes of blood pressure medications (eg, ACE inhibitors, ARBs, thiazide-like diuretics, or dihydropyridine calcium channel blockers) may be used and have shown beneficial cardiovascular outcomes (ADA 2017a).

STEMI: The 2013 ACCF/AHA guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) state that an ACE inhibitor should be initiated within the first 24 hours after STEMI in patients with anterior MI, heart failure, or left ventricular ejection fraction (LVEF) ≤0.4. It is also reasonable to initiate an ACE inhibitor in all patients with STEMI (O'Gara 2013).

CrCl >40 mL/minute: No dosage adjustment necessary.

CrCl <40 mL/minute: Administer 25% of normal dose.

Heart failure post-MI: Initial: 1.25 mg once daily, may increase to 1.25 mg twice daily and then up to a maximum of 2.5 mg twice daily as tolerated.

Hypertension: Initial: 1.25 mg once daily, titrated as tolerated to effect; maximum: 5 mg/day.

Renal artery stenosis: Initial: 1.25 mg once daily; titrate as tolerated to effect.

You should not use this medicine if you are allergic to ramipril or to any other ACE inhibitor, such as benazepril, captopril, fosinopril, enalapril, lisinopril, moexipril, perindopril, quinapril, or trandolapril.

You may also need to avoid taking ramipril with aliskiren if you have kidney disease.

To make sure ramipril is safe for you, tell your doctor if you have:

• kidney disease (or if you are on dialysis);

• liver disease;

• diabetes;

• a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis; or

• if you are also taking telmisartan (Micardis).

Do not use if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Ramipril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control.

It is not known whether ramipril passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Applies to ramipril: oral capsule, oral tablet

Along with its needed effects, ramipril may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ramipril:

• Blurred vision
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• sweating
• unusual tiredness or weakness

• Arm, back, or jaw pain
• chest pain or discomfort
• chest tightness or heaviness
• chills
• cloudy urine
• cold sweats
• decrease in urine output or decrease in urine-concentrating ability
• diarrhea
• fainting
• fast or irregular heartbeat
• shortness of breath

• Seizures
• unexplained bleeding or bruising

Some side effects of ramipril may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Cough

• Nausea
• vomiting

• Feeling of constant movement of self or surroundings
• muscle pain or stiffness
• sensation of spinning
• stomach pain
• weight loss

Applies to ramipril: oral capsule, oral tablet

General

The most common adverse reaction is hypotension.[Ref]

Cardiovascular

Very common (10% or more): Hypotension (11%)
Common (1% to 10%): Angina pectoris, postural hypotension, orthostatic blood pressure decreased
Uncommon (0.1% to 1%): Symptomatic hypotension, myocardial ischemia, myocardial infarction, tachycardia, arrhythmia, palpitation, flushing
Rare (less than 0.1%): Vascular stenosis, hypoperfusion, vasculitis
Frequency not reported: Disturbed orthostatic regulation, Raynaud's phenomenon[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, vomiting, diarrhea, gastrointestinal inflammation, digestive disturbances, abdominal discomfort, dyspepsia
Uncommon (0.1% to 1%): Pancreatitis, pancreatic enzymes increased, abdominal pain, small bowel angioedema, gastritis, constipation, dry mouth
Rare (less than 0.1%): Glossitis
Frequency not reported: Dysphagia, gastroenteritis, increased salivation, gastric pain, aphthous stomatitis[Ref]

Other

Common (1% to 10%): Fatigue, asthenia, vertigo, bronchitis, sinusitis, chest pain
Uncommon (0.1% to 1%): Peripheral edema, pyrexia, libido decreased
Rare (less than 0.1%): Conjunctivitis, hearing impaired, tinnitus
Frequency not reported: Hearing loss, edema, malaise, gynecomastia[Ref]

Respiratory

Common (1% to 10%): Cough, nonproductive tickling cough, cough increased, dyspnea
Uncommon (0.1% to 1%): Bronchospasm, asthma aggravated
Frequency not reported: Eosinophilic pneumonitis, epistaxis, nasal congestion[Ref]

Psychiatric

Uncommon (0.1% to 1%): Depressed mood, anxiety, nervousness, restlessness, sleep disorder
Rare (less than 0.1%): Confusional state
Frequency not reported: Depression, insomnia, disturbance in attention[Ref]

Nervous system

Common (1% to 10%): Headache, dizziness, syncope
Uncommon (0.1% to 1%): Paresthesia, dysgeusia, ageusia, somnolence
Rare (less than 0.1%): Tremor, balance disorder
Frequency not reported: Smell disturbance, amnesia, convulsions, neuralgia, neuropathy, cerebral ischemia, ischemic stroke, transient ischemic attack, psychomotor skills impaired, burning sensation, parosmia[Ref]

Musculoskeletal

Common (1% to 10%): Muscle spasm, myalgia
Uncommon (0.1% to 1%): Arthralgia
Frequency not reported: Arthritis[Ref]

Dermatologic

Common (1% to 10%): Maculopapular rash
Uncommon (0.1% to 1%): Pruritus, hyperhidrosis
Rare (less than 0.1%): Exfoliative dermatitis, urticaria, onycholysis
Frequency not reported: Purpura, pemphigus, pemphigoid, erythema multiforme, toxic epidermal necrolysis, Stevens Johnson syndrome, sweating increased, alopecia, psoriasis aggravated, dermatitis psoriasiform, lichenoid exanthema, enanthema[Ref]

Renal

Common (1% to 10%): Abnormal kidney function
Uncommon (0.1% to 1%): Renal impairment, acute renal failure[Ref]

Metabolic

Common (1% to 10%): Creatinine increased, blood potassium increased
Uncommon (0.1% to 1%): Anorexia, decreased appetite, BUN increased
Frequency not reported: Weight gain, hyponatremia, loss of appetite, uric acid elevated, blood glucose elevated, blood sodium decreased
Postmarketing reports: Hypoglycemia[Ref]

Genitourinary

Uncommon (0.1% to 1%): Worsening of preexisting proteinuria, urine output increased, transient erectile impotence
Frequency not reported: Proteinuria, impotence[Ref]

Ocular

Uncommon (0.1% to 1%): Visual disturbance, blurred vision[Ref]

Hematologic

Uncommon (0.1% to 1%): Eosinophilia, hemoglobin or hematocrit decreased
Rare (less than 0.1%): Neutropenia, agranulocytosis, white blood cell count decreased, red blood cell count decreased, platelet count decreased
Frequency not reported: Pancytopenia, hemolytic anemia, thrombocytopenia, leucopenia, bone marrow failure[Ref]

Hepatic

Uncommon (0.1% to 1%): Hepatic enzymes increased, conjugated bilirubin increased
Rare (less than 0.1%): Cholestatic jaundice, hepatocellular damage
Frequency not reported: Hepatic failure, hepatitis, jaundice, acute liver failure, hepatocellular damage, cholestatic hepatitis, cytolytic hepatitis, serum bilirubin elevated[Ref]

Immunologic

Uncommon (0.1% to 1%): Angioneurotic edema, angioedema
Very rare (less than 0.01%): Photosensitivity
Frequency not reported: Anaphylactic reaction, anaphylactoid reaction, apparent hypersensitivity reaction, antinuclear antibody increased[Ref]

Endocrine

Frequency not reported: Syndrome of inappropriate antidiuretic hormone secretion[Ref]

Some side effects of ramipril may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

CrCl 40 mL/min or less: Reduce usual dose by 25%

CrCl less than 90 mL/min and hypertension: Initial dose: 1.25 mg orally once a day; may titrate up until blood pressure controlled or to maximum dose of 5 mg/day.

CrCl less than 90 mL/min and heart failure: Initial dose: 1.25 mg orally once a day; may increase to 1.25 mg twice daily and to maximum dose of 2.5 mg twice daily.

Renal artery stenosis: Initial dose: 1.25 mg orally once a day

US BOXED WARNING:
-FETAL TOXICITY: When pregnancy is detected, discontinue this drug as soon as possible. Drugs that act directly on the renin angiotensin system (RAS) can cause injury and death to the developing fetus.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.