Fosinopril sodium 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 sodium -treated patients), the usual duration of therapy was two to three months. Discontinuation due to any clinical or laboratory adverse event were 4.1% and 1.1% in fosinopril sodium-treated and placebo-treated patients, respectively. The most frequent reasons (0.4 to 0.9%) were headache, elevated transaminases, fatigue, cough (see PRECAUTIONS: General Cough ), diarrhea, and nausea and vomiting. During clinical trials with any fosinopril sodium 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 sodium alone and at least as frequent on fosinopril sodium as on placebo in placebo-controlled clinical trials are shown in the table below. Clinical Adverse Events in Placebo-Controlled Trials (Hypertension) Fosinopril Sodium (N=688) Incidence (Discontinuation) Placebo (N=184) Incidence (Discontinuation) Cough 2.2 (0.4) 0.0 (0.0) Dizziness 1.6 (0.0) 0.0 (0.0) Nausea/Vomiting 1.2 (0.4) 0.5 (0.0) The following events were also seen at >1% on fosinopril sodium 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 1.0% of patients (excepted as noted) treated with fosinopril sodium 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: Gout, decreased libido. Gastrointestinal: Pancreatitis, hepatitis, dysphagia, abdominal distention, abdominal pain, flatulence, constipation, heartburn, appetite/weight change, dry mouth. Hematologic: Lymphadenopathy. Immunologic: Angioedema. (See WARNINGS: Head and Neck Angioedema and Intestinal Angioedema.) 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 sodium -treated patients), the usual duration of therapy was 3-6 months. Discontinuations due to any clinical or laboratory adverse events, except for heart failure, were 8.0% and 7.5% in fosinopril sodium-treated and placebo-treated patients, respectively. The most frequent reason for discontinuation of fosinopril sodium was angina pectoris (1.1%). Significant hypotension after the first dose of fosinopril sodium 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 relate or of uncertain relationship to therapy, occurring in at least 1% of patients treated with fosinopril sodium 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) Fosinopril Sodium (N=361) Incidence (Discontinuation) Placebo (N=373) Incidence (Discontinuation) Dizziness 11.9 (0.6) 5.4 (0.3) Cough 9.7 (0.8) 5.1 (0.0) Hypotension 4.4 (0.8) 0.8 (0.0) Musculoskeletal Pain 3.3 (0.0) 2.7 (0.0) Nausea/Vomiting 2.2 (0.6) 1.6 (0.3) Diarrhea 2.2 (0.0) 1.3 (0.0) Chest Pain (non-cardiac) 2.2 (0.0) 1.6 (0.0) Upper Respiratory Infection 2.2 (0.0) 1.3 (0.0) Orthostatic Hypotension 1.9 (0.0) 0.8 (0.0) Subjective Cardiac Rhythm Disturbances 1.4 (0.6) 0.8 (0.3) Weakness 1.4 (0.3) 0.5 (0.0) The following events also occurred at a rate of 1% or more on fosinopril sodium, 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 1.0% of patients (except as noted) treated with fosinopril sodium 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 cardio respiratory arrest, shock (0.2%), atrial rhythm disturbance, cardiac rhythm disturbances, non anginal chest pain, edema lower extremity death, syncope, conduction disorder, bradycardia, tachycardia. Dermatologic: Pruritus. Endocrine/Metabolic: Gout, sexual dysfunction. Gastrointestinal: Hepatomegaly, abdominal distension, 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: Anaphylactoid reactions (see WARNINGS: Anaphylactoid and possible related reactions and PRECAUTIONS: Hemodialysis ). 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: Hyperkalemia, (see PRECAUTIONS ), hyponatremia, (see PRECAUTIONS: Drug Interactions, With diuretics ). 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 long standing or markedly elevated blood pressure by any antihypertensive therapy can result in decrease 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 if 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 (see WARNINGS ), 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 Information relating to treatment-emergent adverse events is available in the approved labeling for Bristol-Myers Squibb Company’s fosinopril sodium drug product. However, due to Bristol Myers Squibb’s marketing exclusively rights, this drug product is not labeled for pediatric use.