Summary

Commonly reported side effects of enalapril include: increased blood urea nitrogen and increased serum creatinine. Other side effects include: hypotension. Continue reading for a comprehensive list of adverse effects.

Applies to enalapril: oral extemporaneous suspension, oral tablets, parenteral injection.

Side effects include:

Enalapril in patients with hypertension: Headache, fatigue, dizziness.

Enalapril in patients with heart failure: Orthostatic effects, syncope, chest pain, hypotension, diarrhea, dizziness, cough.

Enalaprilat: Hypotension.

For Healthcare Professionals

Applies to enalapril: compounding powder, intravenous solution, oral liquid, oral tablet.

Cardiovascular

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

Very common (10% or more): Hypotension

Common (1% to 10%): Edema

Uncommon (0.1% to 1%): Angioedema^[Ref]

Nervous system

Very common (10% or more): Headache

Common (1% to 10%): Vertigo, fatigue, peripheral paresthesias, insomnia, dizziness, syncope^[Ref]

Renal

Common (1% to 10%): Increased serum creatinine, uric acid, and potassium^[Ref]

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.^[Ref]

Hepatic

Frequency not reported: Cholestatic jaundice, centrilobular necrosis, fulminant hepatic necrosis, death^[Ref]

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.^[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Photosensitivity, urticaria

Frequency not reported: Angioedema, obstructive laryngeal and glossal angioedema, intestinal angioedema, Henoch-Schonlein purpura^[Ref]

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.^[Ref]

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.^[Ref]

Common (1% to 10%): Dry, nonproductive cough

Frequency not reported: New bronchial hyperactivity, rhinorrhea, exacerbation of obstructive sleep apnea^[Ref]

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.^[Ref]

Rare (less than 0.1%): Neutropenia, agranulocytosis^[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, vomiting, diarrhea

Uncommon (0.1% to 1%): Dysgeusia

Frequency not reported: Pancreatitis, acute small bowel mucosal edema^[Ref]

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.^[Ref]

Dermatologic

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.^[Ref]

Common (1% to 10%): Pruritic, maculopapular eruption

Uncommon (0.1% to 1%): Rash

Frequency not reported: Alopecia, photosensitive lichenoid eruptions, erythema with vasculitis, bullous pemphigoid, pemphigus foliaceous, toxic pustuloderma^[Ref]

Psychiatric

Frequency not reported: Depression, acute psychosis^[Ref]

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.^[Ref]

Endocrine

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.^[Ref]

Frequency not reported: Syndrome of inappropriate ADH secretion, gynecomastia^[Ref]

Musculoskeletal

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.^[Ref]

Frequency not reported: Severe arthralgias and myalgias^[Ref]

Immunologic

Frequency not reported: Positive fluorescent antinuclear antibody test^[Ref]

Genitourinary

Frequency not reported: Vulvovaginal pruritus, dysuria, incontinence^[Ref]