Vasotec Side Effects

Please note - some side effects for Vasotec may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Vasotec - for the Consumer

Vasotec

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 Vasotec:

Diarrhea; dizziness or lightheadedness when sitting up or standing; headache; nausea; persistent, dry cough; tiredness; vomiting.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; hoarseness; infection (eg, fever, sore throat); irregular or slow heartbeat; unusual stomach pain; yellowing of the skin or eyes.

Vasotec Side Effects - for the Professional

Vasotec

Vasotec has been evaluated for safety in more than 10,000 patients, including over 1000 patients treated for one year or more. Vasotec has been found to be generally well tolerated in controlled clinical trials involving 2987 patients.

For the most part, adverse experiences were mild and transient in nature. In clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 3.3 percent of patients with hypertension and in 5.7 percent of patients with heart failure. The frequency of adverse experiences was not related to total daily dosage within the usual dosage ranges. In patients with hypertension the overall percentage of patients treated with Vasotec reporting adverse experiences was comparable to placebo.

HYPERTENSION

Adverse experiences occurring in greater than one percent of patients with hypertension treated with Vasotec in controlled clinical trials are shown below. In patients treated with Vasotec, the maximum duration of therapy was three years; in placebo treated patients the maximum duration of therapy was 12 weeks.

HEART FAILURE

Adverse experiences occurring in greater than one percent of patients with heart failure treated with Vasotec are shown below. The incidences represent the experiences from both controlled and uncontrolled clinical trials (maximum duration of therapy was approximately one year). In the placebo treated patients, the incidences reported are from the controlled trials (maximum duration of therapy is 12 weeks). The percentage of patients with severe heart failure (NYHA Class IV) was 29 percent and 43 percent for patients treated with Vasotec and placebo, respectively.

Other serious clinical adverse experiences occurring since the drug was marketed or adverse experiences occurring in 0.5 to 1.0 percent of patients with hypertension or heart failure in clinical trials are listed below and, within each category, are in order of decreasing severity.

Body As A Whole: Anaphylactoid reactions.

Cardiovascular: Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients; pulmonary embolism and infarction; pulmonary edema; rhythm disturbances including atrial tachycardia and bradycardia; atrial fibrillation; palpitation, Raynaud's phenomenon.

Digestive: Ileus, pancreatitis, hepatic failure, hepatitis (hepatocellular [proven on rechallenge] or cholestatic jaundice), melena, anorexia, dyspepsia, constipation, glossitis, stomatitis, dry mouth.

Hematologic: Rare cases of neutropenia, thrombocytopenia and bone marrow depression.

Musculoskeletal: Muscle cramps.

Nervous/Psychiatric: Depression, confusion, ataxia, somnolence, insomnia, nervousness, peripheral neuropathy (e.g., paresthesia, dysesthesia), dream abnormality.

Respiratory: Bronchospasm, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection, pulmonary infiltrates, eosinophilic pneumonitis.

Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pemphigus, herpes zoster, erythema multiforme, urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity.

Special Senses: Blurred vision, taste alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing.

Urogenital: Renal failure, oliguria, renal dysfunction, flank pain, gynecomastia, impotence.

Miscellaneous: A symptom complex has been reported which may include some or all of the following: a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever, serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash and other dermatologic manifestations.

Angioedema: Angioedema has been reported in patients receiving Vasotec, with an incidence higher in black than in non-black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with Vasotec should be discontinued and appropriate therapy instituted immediately.

Hypotension: In the hypertensive patients, hypotension occurred in 0.9 percent and syncope occurred in 0.5 percent of patients following the initial dose or during extended therapy. Hypotension or syncope was a cause for discontinuation of therapy in 0.1 percent of hypertensive patients. In heart failure patients, hypotension occurred in 6.7 percent and syncope occurred in 2.2 percent of patients. Hypotension or syncope was a cause for discontinuation of therapy in 1.9 percent of patients with heart failure.

Fetal/Neonatal Morbidity and Mortality: See WARNINGS, Fetal/Neonatal Morbidity and Mortality.

Cough: See PRECAUTIONS, Cough.

Pediatric Patients

The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients.

Clinical Laboratory Test Findings

Serum Electrolytes:

Hyperkalemia, hyponatremia.

Creatinine, Blood Urea Nitrogen:

In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 0.2 percent of patients with essential hypertension treated with Vasotec alone. Increases are more likely to occur in patients receiving concomitant diuretics or in patients with renal artery stenosis. In patients with heart failure who were also receiving diuretics with or without digitalis, increases in blood urea nitrogen or serum creatinine, usually reversible upon discontinuation of Vasotec and/or other concomitant diuretic therapy, were observed in about 11 percent of patients. Increases in blood urea nitrogen or creatinine were a cause for discontinuation in 1.2 percent of patients.

Hematology:

Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g percent and 1.0 vol percent, respectively) occur frequently in either hypertension or congestive heart failure patients treated with Vasotec but are rarely of clinical importance unless another cause of anemia coexists. In clinical trials, less than 0.1 percent of patients discontinued therapy due to anemia. Hemolytic anemia, including cases of hemolysis in patients with G-6-PD deficiency, has been reported; a causal relationship to enalapril cannot be excluded.

Liver Function Tests

Elevations of liver enzymes and/or serum bilirubin have occurred.

Side Effects by Body System

Cardiovascular

Cardiovascular side effects, such as hypotension in 2% to 15% and dizziness in 1% to 8% of patients, are more likely in patients with hypovolemia. Enalapril-induced hypotension is usually asymptomatic, but syncope has been reported in 1% of patients. Edema and chest pain have been reported in 3% and 5% of patients, respectively. Angioedema is rare, occurring in approximately 0.2% of patients, and may be due to the effect of enalapril on vasodilating kinins.

Predisposing risk factors for hypotension after enalapril administration are decreased intravascular volume (angiotensin-dependency), hyponatremia, and concurrent use of a diuretic agent.

Nervous system

Nervous system side effects have included headache (3% to 20%). Other nervous system complaints, such as vertigo, fatigue, peripheral paresthesias, and insomnia have been reported in 0.1% to 5% of patients.

Renal

Renal side effects of new or worsened renal insufficiency, presenting as an increased serum creatinine, uric acid, and potassium has occurred in approximately 4% of patients, particularly in patients with "high angiotensin states" (congestive heart failure, edema, renal artery stenosis, or chronic renal failure).

Enalapril, like other angiotensin converting enzyme inhibitors, may decrease serum aldosterone levels, resulting in mild to moderate hyperkalemia. Diuretic use and advanced age increase the risk of renal impairment. Enalapril reduced the risk of renal impairment compared to placebo in diabetic patients. The concomitant use of beta blockers with enalapril has been shown to be renoprotective.

Enalapril may worsen renal insufficiency, especially if the patient is hypovolemic or hypotensive.

Patients with underlying congestive heart failure are predisposed to renal side effects associated with enalapril.

Hepatic

Rare case reports of enalapril-associated hepatitis, where liver function tests rose despite resolution of congestive heart failure, are reported.

A 54-year-old woman with hypertension developed asymptomatic abnormal liver function tests associated with eosinophilia and relatively normal abdominal ultrasonography seven weeks after beginning enalapril. An extensive work-up revealed no evidence of infection; liver biopsy revealed cellular degeneration, portal eosinophilic and mononuclear infiltration, and centrilobular necrosis. The signs and symptoms of hepatitis resolved upon discontinuation of enalapril.

An 80-year-old woman with hypertension and mild heart failure developed hepatomegaly and icterus accompanied by increased conjugated bilirubin, alkaline phosphatase, and aspartate aminotransferase thirty days after beginning enalapril treatment. The patient had not been taking any other medications or herbal products. Tests for hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency returned with normal results. Serology for hepatitis A, B, C and autoimmune screen were negative. Other infectious causes were ruled out. Twenty days after admission, the patient developed grade III encephalopathy and severe coagulation disorders and died 30 days after admission.

In patients with liver dysfunction, frequent monitoring of liver function tests during enalapril administration is recommended.

Hepatic side effects associated with the use of enalapril or other ACE inhibitors have included a rare syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. Experts recommend discontinuation of therapy with this drug if jaundice or markedly elevated hepatic serum enzymes develop. Both cholestatic jaundice and centrilobular necrosis have been described.

Hypersensitivity

Late-onset enalapril-induced angioedema (more than three months) is reported in at least one patient who had taken enalapril without incident for three years. 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.

Hypersensitivity reactions to enalapril, as with some other 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. Obstructive laryngeal and glossal angioedema due to enalapril is a rare, but potentially fatal reaction. 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. Enalapril is not recommended for patients with a history of idiopathic angioedema.

Other hypersensitivity reactions including photosensitivity in 0.1%, or urticaria in 0.3% of patients have been reported. A single case of Henoch-Schonlein purpura has also been reported.

Respiratory

Rare case reports of asthma associated with some angiotensin converting enzyme inhibitors suggest that these drugs seem to play a role in the genesis and metabolism of bronchodilatory mediators. For this reason, some experts recommend cautious use of enalapril in patients with preexisting asthma.

A retrospective study has revealed a significantly higher incidence of discontinuation of angiotensin converting enzyme (ACE) inhibitor therapy due to cough among black patients compared with non-black patients (9.6% vs. 2.4%).

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.

Respiratory side effects have included a dry, nonproductive cough which can be a problem for 1% to 5% of patients. Some patients with enalapril-induced cough have demonstrated new bronchial hyperactivity. Less common respiratory system side effects have included rhinorrhea, which is thought to be due to the effect of enalapril on vasodilating kinins. In addition, ACE inhibitors have been associated with exacerbation of obstructive sleep apnea symptoms due to ACEI-induced upper airway inflammation.

Hematologic

Rare, reversible cases of agranulocytosis associated with enalapril and other angiotensin converting enzyme (ACE) inhibitors have been reported. ACE inhibitors have been used to treat post renal transplant erythrocytosis. Data have shown that they may decrease circulating erythropoietin levels in these patients.

Hematologic side effects are extremely rare. Discontinuation of enalapril due to anemia has been reported in less than 0.1% of patients. Rare cases of neutropenia and agranulocytosis have been reported.

Gastrointestinal

A 56-year-old woman with hypertension and diabetes developed acute abdominal pain, nausea, and vomiting associated upper abdominal tenderness, hyperamylasemia, hyperlipasemia, and normal upper abdominal ultrasonography within 24 hours of starting enalapril. The signs and symptoms of pancreatitis resolved over the next several days once the drug was discontinued. No rechallenge was performed.

A 65-year-old woman was diagnosed with acute pancreatitis by ultrasonography, CT scan, and serum amylase level of 980 units/L. The patient had been receiving enalapril, HCTZ, and amiloride for one year. The pancreatitis resolved over 7 days. The patient upon rechallenge with enalapril developed severe upper abdominal pain, vomiting, and hypotension. CT scan showed intrapancreatic necrosis and peripancreatic fluid. Four weeks later a CT scan showed three pseudocysts that took 4 months to resolve. The author of the report concluded that rechallenging patients who develop acute pancreatitis while on enalapril is not recommended.

Gastrointestinal side effects are unusual. Nausea, vomiting, or diarrhea has each been reported in less than 3% of patients. Dysgeusia is rare, occurring in less than 0.5% of patients. Rare cases of pancreatitis and acute small bowel mucosal edema associated with enalapril have been reported.

Dermatologic

Dermatologic side effects reported most commonly include a pruritic, maculopapular eruption on the upper trunk and arms, in approximately 1.5% of patients. (Only 0.4% of patients have discontinued therapy due to rash.) Rare dermatologic side effects have included alopecia, photosensitive lichenoid eruptions, erythema with vasculitis, bullous pemphigoid, pemphigus foliaceous and toxic pustuloderma.

A 52-year-old Korean woman with hypertension experienced a generalized, erythematous, scaly rash associated with a positive Nikolsky sign and biopsy results consistent with pemphigus foliaceous within three weeks after beginning enalapril. Direct immunofluorescence revealed intercellular IgG deposition. The pemphigus remained active at least 12 months after enalapril was discontinued.

A 35-year-old woman with hypertension developed alopecia during enalapril therapy, which resolved upon discontinuation of the drug, and recurred upon rechallenge.

A 77-year-old man with heart failure developed a generalized morbilliform rash after starting enalapril. Biopsy was consistent with toxic pustuloderma.

Psychiatric

A 52-year-old woman with hypertension and a history of depression associated with the use of beta-blockers, developed fatigue, malaise, and clinical signs and symptoms of depression, including suicidal ideation, within five weeks after starting enalapril. The depression gradually resolved with substitution of a thiazide diuretic and a low sodium diet. Rechallenge resulted in recurrent depression.

A 41-year-old man with hypertension became agitated, anxious, depressed, and unable to sleep four weeks after starting enalapril. The psychosis resolved when enalapril was stopped, and recurred upon rechallenge.

Psychiatric problems associated with enalapril have been rarely reported, and include depression and acute psychosis.

Endocrine

Endocrinologic side effects have included the syndrome of inappropriate ADH secretion and gynecomastia (rare). Limited data have shown that the use of ACE inhibitors is an independent risk factor for the development of hypoglycemia in some diabetic patients.

A 69-year-old woman with diabetes mellitus and hypertension developed symptomatic hyponatremia associated with decreased plasma and increased urine osmolalities, normal thyroid and basal cortisol studies, and a positive water load test four months after beginning enalapril. The syndrome resolved upon discontinuation of enalapril, and recurred upon rechallenge.

Musculoskeletal

Musculoskeletal complaints have included severe arthralgias and myalgias which have rarely been associated with some ACE inhibitors, including enalapril.

A 76-year-old woman with hypertension, on enalapril monotherapy for three weeks, developed progressive myalgias, asthenia, morning stiffness, and weakness associated with no abnormal laboratory values. Due to the absence of other apparent causes, enalapril was discontinued, and the patient's myalgias disappeared. In at least one other case, rechallenge resulted in recurrent symptoms.

Immunologic

Immunologic side effects have been reported in a limited study of nine elderly patients, three of whom developed a positive fluorescent antinuclear antibody test during six weeks of enalapril therapy.

Genitourinary

Genitourinary side effects rarely reported include vulvovaginal pruritus, dysuria, and incontinence, and have been associated with the use of enalapril in an elderly patient.

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