Ramipril Side Effects

Brand Names: Altace

Please note - some side effects for Ramipril may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Ramipril - for the Consumer

Ramipril

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Ramipril:

Cough; dizziness; headache; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur when using Ramipril:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the hands, eyes, mouth, face, lips, throat, or tongue; hoarseness); chest pain; dark urine; decreased urination; difficulty swallowing; infection (eg, fever, chills, persistent sore throat); irregular heartbeat; loss of appetite; pale stools; red, swollen, blistered, or peeling skin; seizures; stomach pain (with or without nausea or vomiting); symptoms of low blood pressure (eg, fainting, severe dizziness, lightheadedness); yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Ramipril Capsules

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Ramipril Capsules:

Cough; dizziness; headache; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur when using Ramipril Capsules:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the hands, eyes, mouth, face, lips, throat, or tongue; hoarseness); chest pain; dark urine; decreased urination; difficulty swallowing; infection (eg, fever, chills, persistent sore throat); irregular heartbeat; loss of appetite; pale stools; red, swollen, blistered, or peeling skin; seizures; stomach pain (with or without nausea or vomiting); symptoms of low blood pressure (eg, fainting, severe dizziness, lightheadedness); yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch .

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Ramipril Side Effects - for the Professional

Ramipril

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hypertension

Ramipril has been evaluated for safety in over 4000 patients with hypertension; of these, 1230 patients were studied in U.S. controlled trials, and 1107 were studied in foreign controlled trials. Almost 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was similar in Ramipril and placebo patients. The most frequent clinical side effects (possibly or probably related to study drug) reported by patients receiving Ramipril in placebo-controlled trials were: headache (5.4%), dizziness (2.2%), and fatigue or asthenia (2.0%), but only the last one was more common in Ramipril patients than in patients given placebo. Generally the side effects were mild and transient, and there was no relation to total dosage within the range of 1.25 mg to 20 mg. Discontinuation of therapy because of a side effect was required in approximately 3% of U.S. patients treated with Ramipril. The most common reasons for discontinuation were: cough (1.0%), dizziness (0.5%), and impotence (0.4%).

Of observed side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with Ramipril, only asthenia (fatigue) was more common on Ramipril than placebo (2% [n = 13/651] vs. 1% [n = 2/286], respectively).

In placebo-controlled trials, there was also an excess of upper respiratory infection and flu syndrome in the Ramipril group, not attributed at that time to Ramipril. As these studies were carried out before the relationship of cough to ACE inhibitors was recognized, some of these events may represent Ramipril-induced cough. In a later 1 year study, increased cough was seen in almost 12% of Ramipril patients, with about 4% of patients requiring discontinuation of treatment.

Other Adverse Reactions

Other adverse reactions reported in controlled clinical trials (in less than 1% of Ramipril patients), or rarer events seen in postmarketing experience, include the following (in some, a causal relationship to drug is uncertain):

Body as a whole: Anaphylactoid reactions [see Warnings and Precautions (5.1)].

Cardiovascular: Symptomatic hypotension (reported in 0.5% of patients in U.S. trials) [see Warnings and Precautions(5.5)], syncope, and palpitations.

Hematologic: Pancytopenia, hemolytic anemia, and thrombocytopenia. Decreases in hemoglobin or hematocrit (a low value and a decrease of 5 g/dL or 5%, respectively) were rare, occurring in 0.4% of patients receiving Ramipril alone and in 1.5% of patients receiving Ramipril plus a diuretic.

Renal: Acute renal failure. Some hypertensive patients with no apparent preexisting renal disease have developed minor, usually transient, increases in blood urea nitrogen and serum creatinine when taking Ramipril, particularly when Ramipril was given concomitantly with a diuretic [see Warnings and Precautions (5.3)].

Angioneurotic edema: Angioneurotic edema has been reported in 0.3% of patients in U.S. clinical trials of Ramipril [seeWarnings and Precautions (5.1)].

Gastrointestinal: Hepatic failure, hepatitis, jaundice, pancreatitis, abdominal pain (sometimes with enzyme changes suggesting pancreatitis), anorexia, constipation, diarrhea, dry mouth, dyspepsia, dysphagia, gastroenteritis, increased salivation, and taste disturbance.  

 Dermatologic: Apparent hypersensitivity reactions (manifested by urticaria, pruritus, or rash, with or without fever), photosensitivity, purpura, onycholysis, pemphigus, pemphigoid, erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome.  

Neurologic and Psychiatric: Anxiety, amnesia, convulsions, depression, hearing loss, insomnia, nervousness, neuralgia, neuropathy, paresthesia, somnolence, tinnitus, tremor, vertigo, and vision disturbances.  

Miscellaneous: As with other ACE inhibitors, a symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, photosensitivity, rash and other dermatologic manifestations. Additionally, as with other ACE inhibitors, eosinophilic pneumonitis has been reported.

Other: Arthralgia, arthritis, dyspnea, edema, epistaxis, impotence, increased sweating, malaise, myalgia, and weight gain.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, there have been rare reports of hypoglycemia reported during Ramipril therapy when given to patients concomitantly taking oral hypoglycemic agents or insulin. The causal relationship is unknown.

Clinical Laboratory Test Findings

Creatinine and Blood Urea Nitrogen: Increases in creatinine levels occurred in 1.2% of patients receiving Ramipril alone, and in 1.5% of patients receiving Ramipril and a diuretic. Increases in blood urea nitrogen levels occurred in 0.5% of patients receiving Ramipril alone and in 3% of patients receiving Ramipril with a diuretic. None of these increases required discontinuation of treatment. Increases in these laboratory values are more likely to occur in patients with renal insufficiency or those pretreated with a diuretic and, based on experience with other ACE inhibitors, would be expected to be especially likely in patients with renal artery stenosis [see Warnings and Precautions (5.3)]. As Ramipril decreases aldosterone secretion, elevation of serum potassium can occur. Use potassium supplements and potassium sparing diuretics with caution, and monitor the patient’s serum potassium frequently [see Warnings and Precautions (5.8)].

Hemoglobin and Hematocrit: Decreases in hemoglobin or hematocrit (a low value and a decrease of 5 g/dL or 5%, respectively) were rare, occurring in 0.4% of patients receiving Ramipril alone and in 1.5% of patients receiving Ramipril plus a diuretic. No U.S. patients discontinued treatment because of decreases in hemoglobin or hematocrit.

Other (causal relationships unknown): Clinically important changes in standard laboratory tests were rarely associated with Ramipril administration. Elevations of liver enzymes, serum bilirubin, uric acid, and blood glucose have been reported, as have cases of hyponatremia and scattered incidents of leucopenia, eosinophilia, and proteinuria. In U.S. trials, less than 0.2% of patients discontinued treatment for laboratory abnormalities; all of these were cases of proteinuria or abnormal liver-function tests.

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Side Effects by Body System - for Healthcare Professionals

General

Ramipril is generally well-tolerated. Most side effects are reported as often in patients taking placebo. Less than 3% of patients discontinue ramipril due to an adverse drug event.

Nervous system

Nervous system side effects include headache, dizziness, and lightheadedness in 2% to 5% of patients. Asthenia and fatigue occur in 2% of patients.

Cardiovascular

Cardiovascular problems are limited mainly to hypotension in 0.5% of patients. Angioneurotic edema is reported in 0.1% to 0.5% of patients, and may be fatal.

The exact mechanism by which ACE inhibitors produce angioedema is not well known, but is believed to involve stimulation of the kallikrein-kinin system, particularly in patients who are genetically or environmentally predisposed.

Gastrointestinal

Rare cases of abdominal pain associated with elevated enzymes suggestive of pancreatitis are reported.

Gastrointestinal complaints of nausea or dyspepsia are reported in approximately 1% of patients. Rare problems include general abdominal pain or fullness, dry mouth, dysphasia, constipation, diarrhea, gastroenteritis, anorexia, vomiting, increased salivation, and dysgeusia.

Respiratory

Respiratory side effects are limited to an idiosyncratic and reversible cough in approximately 3% of patients.

Several agents have been studied for treating cough with ACE inhibitors. No long term trials exist to allow a definitive treatment option. Cromolyn has the most data showing some benefit. Other agents studied include baclofen, theophylline, sulindac, and benzonatate.

Renal

In one study of 13 patients with congestive heart failure, mean creatinine clearance increased during ramipril therapy.

Renal insufficiency occurs in approximately 1% to 2% of patients and is usually transient. In general, ACE inhibitor-induced renal insufficiency is much more likely in sodium- or intravascular volume-depleted patients, or in those patients on concomitant diuretic therapy.

Metabolic

Metabolic changes include significant increases in serum potassium in 1% to 2% of patients. Extremely rare cases of hyponatremia have been associated with the use of ramipril (and other ACE inhibitors) in the elderly.

Ramipril has not been associated with deleterious changes in blood glucose or serum lipids in patients with diabetes mellitus.

Increases in serum potassium are associated with ACE inhibitors because they decrease aldosterone secretion, which usually promotes renal potassium excretion.

The mechanism of hyponatremia (rare) is unknown. Hyponatremia associated with ACE inhibitors presents like SIADH and may be due to inhibition of bradykinin metabolism or direct stimulation of ADH secretion by angiotensin II in the central nervous system (angiotensin I accumulates during ACE inhibitor therapy and crosses the blood-brain barrier).

Ramipril, like other ACE inhibitors does not appear to exert a significant effect on plasma glucose, insulin, or C-peptide levels.

Genitourinary

Genitourinary complaints are limited to impotence in 0.4% of patients.

Hypersensitivity

Hypersensitivity reactions to angiotensin converting enzyme (ACE) inhibitors may be life threatening. Angioedema of the face, extremities, lips, tongue, glottis and/or pharynx have been reported rarely in patients receiving ACE inhibitors. In addition, intestinal angioedema has been reported in patients treated with ACE inhibitors. It is recommended that any patient with dyspnea, dysphagia, or significant facial angioedema stop therapy immediately and avoid ACE inhibitor therapy in general.

Dermatitis, pruritus, and photosensitivity have also been reported.

Patients with intestinal angioedema generally present with abdominal pain (with or without nausea or vomiting) and in some cases there was no prior history of facial angioedema, and C-1 esterase levels were normal. These symptoms resolve after stopping the ACE inhibitor.

Hematologic

Hematologic side effects including agranulocytosis have been associated with ACE inhibitors including ramipril.

ACE inhibitors have been used to treat post renal transplant erythrocytosis. Data have shown that they may decrease circulating erythropoietin levels in these patients.

Musculoskeletal

Musculoskeletal pains--both arthralgias and myalgias--have rarely been associated with the use of some ACE inhibitors, including ramipril.

Dermatologic

Dermatologic side effects are typically the result of hypersensitivity reactions. Rare cases of pemphigus, including lichen planus pemphigoides, have been associated with the use of ramipril and other ACE inhibitors. In addition, Stevens-Johnson syndrome has been associated with ramipril therapy.

Drug-induced pemphigus has also been associated with a related drug, captopril. The mechanism remains unknown but drugs containing a thiol group may be involved as they are able to produce acantholysis of epidermal cells in vitro. Drugs containing an amide group have also been associated with pemphigus. These include enalapril which also induced acantholysis in vitro. (Four cases of enalapril-induced pemphigus have been reported.) Spontaneous remission of the skin lesions after drug withdrawal is less common with drugs containing the amide group compared with drugs containing the thiol group (15% vs. 50%).

Hepatic

Hepatic side effects including hepatic failure, hepatitis, jaundice and pancreatitis have been reported rarely.

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