Fosinopril adverse reactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [2], Ahmed Zaghw, M.D. [3]
Fosinopril
Fosinopril and Hydrochlorothiazide
Overview
Captopril 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
Fosinopril has been evaluated for safety in more than 2100 individuals in hypertension and heart failure trials, including approximately 530 patients treated for a year or more. Generally adverse events were mild and transient, and their frequency was not prominently related to dose within the recommended daily dosage range.
Hypertension
In placebo-controlled clinical trials (688 fosinopril-treated patients), the usual duration of therapy was two to three months. Discontinuations due to any clinical or laboratory adverse event were 4.1% and 1.1% in fosinopril-treated and placebo-treated patients, respectively. The most frequent reasons (0.4 to 0.9%) were headache, elevated transaminases, fatigue, cough, diarrhea, and nausea and vomiting.
During clinical trials with any fosinopril regimen, the incidence of adverse events in the elderly ≥65 years old) was similar to that seen in younger patients.
Clinical adverse events probably or possibly related or of uncertain relationship to therapy, occurring in at least 1% of patients treated with fosinopril alone and at least as frequent on fosinopril as on placebo in placebo-controlled clinical trials are shown in the table below.
Clinical Adverse Events in Placebo-Controlled Trials (Hypertension)
The following events were also seen at >1% on fosinopril but occurred in the placebo group at a greater rate: headache, diarrhea, fatigue, and sexual dysfunction. Other clinical events probably or possibly related, or of uncertain relationship to therapy occurring in 0.2 to 1% of patients (except as noted) treated with fosinopril in controlled or uncontrolled clinical trials (N = 1479) and less frequent, clinically significant events include (listed by body system):
General
Chest pain, edema, weakness,excessive sweating.
Cardiovascular
Angina/myocardial infarction, cerebrovascular accident, hypertensive crisis, rhythm disturbances, palpitations, hypotension, syncope, flushing, claudication.
Orthostatic
Hypotension occurred in 1.4% of patients treated with fosinopril monotherapy. Hypotension or orthostatic hypotension was a cause for discontinuation of therapy in 0.1% of patients.
Dermatologic
Urticaria, rash, photosensitivity, pruritus.
Endocrine/Metabolic
Gastrointestinal
Pancreatitis, hepatitis, dysphagia, abdominal distention, abdominal pain, flatulence, constipation, heartburn, appetite/weight change, dry mouth.
Hematologic
Immunologic
Musculoskeletal
Arthralgia, musculoskeletal pain, myalgia/muscle cramp.
Nervous/Psychiatric
Memory disturbance, tremor, confusion, mood change, paresthesia, sleep disturbance, drowsiness, vertigo.
Respiratory
Bronchospasm, pharyngitis, sinusitis/rhinitis, laryngitis/hoarseness, epistaxis. A symptom-complex of cough, bronchospasm, and eosinophilia has been observed in two patients treated with fosinopril.
Special Senses
Tinnitus, vision disturbance, taste disturbance, eye irritation.
Urogenital
Renal insufficiency, urinary frequency.
Heart Failure
In placebo-controlled clinical trials (361 fosinopril-treated patients), the usual duration of therapy was 3 to 6 months. Discontinuations due to any clinical or laboratory adverse event, except for heart failure, were 8% and 7.5% in fosinopril-treated and placebo-treated patients, respectively. The most frequent reason for discontinuation of fosinopril was angina pectoris (1.1%). Significant hypotension after the first dose of fosinopril occurred in 14/590 (2.4%) of patients; 5/590 (0.8%) patients discontinued due to first dose hypotension.
Clinical adverse events probably or possibly related or of uncertain relationship to therapy, occurring in at least 1% of patients treated with fosinopril and at least as common as the placebo group, in placebo-controlled trials are shown in the table below.
Clinical Adverse Events in Placebo-Controlled Trials (Heart Failure)
The following events also occurred at a rate of 1% or more on fosinopril but occurred on placebo more often: fatigue, dyspnea, headache, rash, abdominal pain, muscle cramp, angina pectoris, edema, and insomnia.
The incidence of adverse events in the elderly (≥65 years old) was similar to that seen in younger patients.
Other clinical events probably or possibly related, or of uncertain relationship to therapy occurring in 0.4 to 1% of patients (except as noted) treated with fosinopril in controlled clinical trials (N = 516) and less frequent, clinically significant events include (listed by body system):
General
Fever, influenza, weight gain, hyperhidrosis, sensation of cold, fall, pain.
Cardiovascular
Sudden death, cardiorespiratory arrest, shock (0.2%), atrial rhythm disturbance, cardiac rhythm disturbances, non anginal chest pain, edema lower extremity, hypertension, syncope, conduction disorder, bradycardia, tachycardia.
Dermatologic
Endocrine/Metabolic
Gastrointestinal
Hepatomegaly, abdominal distention, decreased appetite, dry mouth, constipation, flatulence.
Immunologic
Angioedema (0.2%).
Musculoskeletal
Muscle ache, swelling of an extremity, weakness of an extremity.
Nervous/Psychiatric
Cerebral infarction, TIA, depression, numbness, paresthesia, vertigo, behavior change, tremor.
Respiratory
Abnormal vocalization, rhinitis, sinus abnormality, tracheobronchitis, abnormal breathing, pleuritic chest pain.
Special Senses
Vision disturbance, taste disturbance.
Urogenital
Abnormal urination, kidney pain.
Potential Adverse Effects Reported with ACE Inhibitors
Body as a Whole
Other medically important adverse effects reported with ACE inhibitors include: Cardiac arrest; eosinophilic pneumonitis; neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), thrombocytopenia; acute renal failure; hepatic failure, jaundice (hepatocellular or cholestatic); symptomatic hyponatremia; bullous pemphigus, exfoliative dermatitis; a syndrome which may include: arthralgia/ arthritis, vasculitis, serositis, myalgia, fever, rash or other dermatologic manifestations, a positive ANA, leukocytosis, eosinophilia, or an elevated ESR.
Laboratory Test Abnormalities
Serum Electrolytes
BUN/Serum Creatinine
Elevations, usually transient and minor, of BUN or serum creatinine have been observed. In placebo-controlled clinical trials, there were no significant differences in the number of patients experiencing increases in serum creatinine (outside the normal range or 1.33 times the pre-treatment value) between the fosinopril and placebo treatment groups. Rapid reduction of longstanding or markedly elevated blood pressure by any antihypertensive therapy can result in decreases in the glomerular filtration rate, and in turn, lead to increases in BUN or serum creatinine. (See PRECAUTIONS, General.)
Hematology
In controlled trials, a mean hemoglobin decrease of 0.1 g/dL was observed in fosinopril-treated patients. In individual patients decreases in hemoglobin or hematocrit were usually transient, small, and not associated with symptoms. No patient was discontinued from therapy due to the development of anemia.
Other
Neutropenia, leukopenia and eosinophilia.
Liver Function Tests
Elevations of transaminases, LDH, alkaline phosphatase and serum bilirubin have been reported. Fosinopril therapy was discontinued because of serum transaminase elevations in 0.7% of patients. In the majority of cases, the abnormalities were either present at baseline or were associated with other etiologic factors. In those cases which were possibly related to fosinopril therapy, the elevations were generally mild and transient and resolved after discontinuation of therapy.
Pediatric Patients
The adverse experience profile for pediatric patients is similar to that seen in adult patients with hypertension. The long-term effects of fosinopril on growth and development have not been studied.[1]
References
Adapted from the FDA Package Insert.