Lisinopril adverse reactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2], Amr Marawan, M.D. [3]
Lisinopril
Lisinopril and Hydrochlorothiazide tablet
Overview
Lisinopril tablet is an angiontensin converting enzyme inhibitor drug that is FDA approved for the treatment of hypertension, heart failure, left ventricular dysfunction after myocardial infarction, diabetic nephropathy. Adverse reactions include hypotension, rash, hyperkalemia, disorder of taste, cough. hypotension, rash, hyperkalemia, disorder of taste, cough.
Category
Antihypertensive Agents, Angiotensin Converting Enzyme Inhibitors. Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [5]
Adverse Reactions
Lisinopril have been found to be generally well tolerated in controlled clinical trials involving 1969 patients with hypertension or heart failure. For the most part, adverse experiences were mild and transient.
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 are listed in the table below:
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Chest pain and back pain were also seen, but were more common on placebo than 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 11.0% 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 frequently on lisinopril than placebo.
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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.
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 (2.0%), 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 1.0% 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
Metabolic
Weight loss, dehydration, fluid overload, gout, weight gain.
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. 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 alteration.
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%). 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.
Hypotension
In hypertensive patients, hypotension occurred in 1.2% and syncope occurred in 0.1% of 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 causes for discontinuation of therapy in 1.8% of these patients. 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.
Fetal/Neonatal Morbidity and Mortality
See WARNINGS, Fetal/Neonatal Morbidity and Mortality.
Cough
See PRECAUTIONS - Cough
Clinical Laboratory Test Findings
Serum Electrolytes: Hyperkalemia (see PRECAUTIONS), hyponatremia.
Creatinine, Blood Urea Nitrogen
Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2.0% of patients with essential hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in approximately 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased.
Hemoglobin and Hematocrit
Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol%, respectively) occurred frequently in patients treated with lisinopril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia.
Liver Function Tests
Rarely, elevations of liver enzymes and/or serum bilirubin have occurred.
In hypertensive patients, 2.0% discontinued therapy due to laboratory adverse experiences, principally elevations in blood urea nitrogen (0.6%), serum creatinine (0.5%), and serum potassium (0.4%).
In the heart failure trials, 3.4% of patients discontinued therapy due to laboratory adverse experiences; 1.8% due to elevations in blood urea nitrogen and/or creatinine, and 0.6% due to elevations in serum potassium. In the myocardial infarction trial, 2.0% of patients receiving lisinopril discontinued therapy due to renal dysfunction (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration); less than 1.0% of patients discontinued therapy due to other laboratory adverse experiences: 0.1 % with hyperkalemia and less than 0.1% with hepatic enzyme alterations.[1]
References
Adapted from the FDA Package Insert.