Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect
the rates observed in practice.
The following adverse reactions (events 2% greater on PRINIVIL than on placebo) were observed with PRINIVIL vs placebo: headache (5.7% vs 1.9%), dizziness (5.4% vs 1.9%), cough (3.5% vs 1.0%).
In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with PRINIVIL for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks.
The following adverse reactions (events 2% greater on PRINIVIL than on placebo) were observed with PRINIVIL vs placebo: hypotension (4.4% vs 0.6%), chest pain (3.4% vs 1.3%).
In the ATLAS trial [see Clinical Studies (14.2)] in heart failure patients, withdrawals for adverse reactions were similar in the low- and high-dose groups. The following adverse
reactions, mostly related to ACE inhibition, were reported more commonly in the high dose group:
Table 1: Dose-related Adverse Drug Reactions: ATLAS trial
Acute Myocardial Infarction
Patients in the GISSI-3 study, treated with PRINIVIL, had a higher incidence of hypotension (9.0% vs 3.7%) and renal dysfunction (2.4% vs 1.1%) compared with patients not taking PRINIVIL.
Other clinical adverse reactions occurring in 1% or higher of patients with hypertension or heart failure treated with PRINIVIL in controlled clinical trials and do not appear in other sections of labeling are listed below:
Body as a whole: Fatigue, asthenia, orthostatic effects.
Digestive: Pancreatitis, constipation, flatulence, dry mouth, diarrhea.
Hematologic: Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia.
Endocrine: Diabetes mellitus, inappropriate antidiuretic hormone secretion.
Skin: Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, Stevens – Johnson syndrome, and pruritus.
Special Senses: Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances, olfactory disturbances.
Miscellaneous: A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia,
leukocytosis, paresthesia and vertigo. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms.
Clinical Laboratory Test Findings
Serum Potassium: In clinical trials hyperkalemia (serum potassium >5.7 mEq/L) occurred in 2.2% and 4.8% of PRINIVIL-treated patients with hypertension and heart failure, respectively
[see Warnings and Precautions (5.5)].
Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension
treated with PRINIVIL alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis [see Warnings and Precautions (5.4)]. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage
of the diuretic was decreased.
Patients with acute myocardial infarction in the GISSI-3 trial treated with PRINIVIL had a higher (2.4% versus 1.1% in placebo) incidence of renal dysfunction in-hospital and at 6 weeks (increasing creatinine concentration
to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration).
Hemoglobin and Hematocrit: Small decreases in hemoglobin (mean 0.4 mg/dL) and hematocrit (mean 1.3%) occurred frequently in patients treated with PRINIVIL but were rarely of clinical importance
in patients without some other cause of anemia. In clinical trials, fewer than 0.1% of patients discontinued therapy for anemia.
Rarely, elevations of liver enzymes and/or serum bilirubin have occurred [see Warnings and Precautions (5.6)].