Lisinopril Adverse Effects

Hypertension
In clinical trials in patients with hypertension treated with lisinopril, discontinuation of therapy due to clinical adverse experiences occurred in 5.7% of patients. The overall frequency of adverse experiences could not be related to total daily dosage within the recommended therapeutic dosage range.

For adverse experiences occurring in greater than 1% of patients with hypertension treated with lisinopril or lisinopril plus hydrochlorothiazide in controlled clinical trials, and more frequently with lisinopril and/or lisinopril plus hydrochlorothiazide than placebo, comparative incidence data data are listed in the table below:



Chest and back pain were also seen but were more common on placebo then lisinopril.

Heart Failure
In patients with heart failure treated with lisinopril for up to four years, discontinuation of therapy due to clinical adverse experiences occurred in 11% of patients. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with lisinopril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks. The following table lists those adverse experiences which occurred in greater than 1% of patients with heart failure treated with lisinopril or placebo for up to 12 weeks in controlled clinical trials, and more on lisinopril than placebo.



Also observed at > 1% with lisinopril but more frequent or as frequent on placebo than lisinopril in controlled trials were asthenia, angina pectoris, nausea, dyspnea, cough, and pruritus.

Worsening of heart failure, anorexia, increased salivation, muscle cramps, back pain, myalgia, depression, chest sound abnormalities, and pulmonary edema were also seen in controlled clinical trials, but were more common on placebo than lisinopril. In the two-dose ATLAS trial in heart failure patients, withdrawals due to adverse events were not different between the low and high groups, either in total number of discontinuation (17 to 18%) or in rare specific events (<1%). The following adverse events, mostly related to ACE inhibition, were reported more commonly in the high dose group:



Acute Myocardial Infarction
In the GISSI-3 trial, in patients treated with lisinopril for six weeks following acute myocardial infarction, discontinuation of therapy occurred in 17.6% of patients.

Patients treated with lisinopril had a significantly higher incidence of hypotension and renal dysfunction compared with patients not taking lisinopril.

In the GISSI-3 trial, hypotension (9.7%), renal dysfunction (2%), cough (0.5%), post infarction angina (0.3%), skin rash and generalized edema (0.01%), and angioedema (0.01%) resulted in withdrawal of treatment. In elderly patients treated with lisinopril, discontinuation due to renal dysfunction was 4.2%.

Other clinical adverse experiences occurring in 0.3% to 1% of patients with hypertension or heart failure treated with lisinopril in controlled clinical trials and rarer, serious, possibly drug-related events reported in uncontrolled studies or marketing experience are listed below, and within each category are in order of decreasing severity:

Body as a Whole
Anaphylactoid reactions, syncope, orthostatic effects, chest discomfort, pain, pelvic pain, flank pain, edema, facial edema, virus infection, fever, chills, malaise.

Cardiovascular
Cardiac arrest; myocardial infarction or cerebrovascular accident possibly secondary to excessive hypotension in high risk patients; pulmonary embolism and infarction, arrhythmias (including ventricular tachycardia, atrial tachycardia, atrial fibrillation, bradycardia and premature ventricular contractions), palpitations, transient ischemic attacks, paroxysmal nocturnal dyspnea, orthostatic hypotension, decreased blood pressure, peripheral edema, vasculitis.

Digestive
Pancreatitis, hepatitis (hepatocellular or cholestatic jaundice), vomiting, gastritis, dyspepsia, heartburn, gastrointestinal cramps, constipation, flatulence, dry mouth.

Hematologic
Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia.

Endocrine
Diabetes mellitus.

Metabolic
Weight loss, dehydration, fluid overload, gout, weight gain.
 * Cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin have been reported in post-marketing experience

Musculoskeletal
Arthritis, arthralgia, neck pain, hip pain, low back pain, joint pain, leg pain, knee pain, shoulder pain, arm pain, lumbago.

Nervous System/Psychiatric
Stroke, ataxia, memory impairment, tremor, peripheral neuropathy (e.g., dysesthesia), spasm, paresthesia, confusion, insomnia, somnolence, hypersomnia, irritability and nervousness.

Respiratory System
Malignant lung neoplasms, hemoptysis, pulmonary infiltrates, bronchospasm, asthma, pleural effusion, pneumonia, eosinophilic pneumonitis, bronchitis, wheezing, orthopnea, painful respiration, epistaxis, laryngitis, sinusitis, pharyngeal pain, pharyngitis, rhinitis, rhinorrhea.

Skin
Urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema, flushing, diaphoresis, cutaneous pseudolymphoma. Other severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson syndrome; causal relationship has not been established.

Special Senses
Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances.

Urogenital System
Acute renal failure, oliguria, anuria, uremia, progressive azotemia, renal dysfunction, pyelonephritis, dysuria, urinary tract infection, breast pain.

Miscellaneous
A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia and leukocytosis. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms.

Angioedema
Angioedema has been reported in patients receiving lisinopril (0.1%) 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 lisinopril should be discontinued and appropriate therapy instituted immediately. In rare cases, intestinal angioedema has been reported in post marketing experience.

Hypotension
In hypertensive patients, hypotension occurred in 1.2% and syncope occurred in 0.1% of patients with an incidence higher in Black than in non-Black patients. Hypotension or syncope was a cause of discontinuation of therapy in 0.5% of hypertensive patients. In patients with heart failure, hypotension occurred in 5.3% and syncope occurred in 1.8% of patients. These adverse experiences were possibly dose-related (see above data from ATLAS Trial) and caused discontinuation of therapy in 1.8% of these patients in the symptomatic trials. In patients treated with lisinopril for six weeks after acute myocardial infarction, hypotension (systolic blood pressure <100 mmHg) resulted in discontinuation of therapy in 9.7% of the patients.

Pediatric Patients
No relevant differences between the adverse experience profile for pediatric patients and that previously reported for adult patients were identified.