INSPRA SIDE EFFECTS

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Hyperkalemia.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

Heart Failure Post-Myocardial Infarction

In EPHESUS, safety was evaluated in 3307 patients treated with INSPRA and 3301 placebo-treated patients. The overall incidence of adverse events reported with INSPRA (78.9%) was similar to placebo (79.5%). Adverse events occurred at a similar rate regardless of age, gender, or race. Patients discontinued treatment due to an adverse event at similar rates in either treatment group (4.4% INSPRA vs. 4.3% placebo), with the most common reasons for discontinuation being hyperkalemia, MI, and abnormal renal function.

Adverse reactions that occurred more frequently in patients treated with INSPRA than placebo were hyperkalemia (3.4% vs. 2.0%) and increased creatinine (2.4% vs. 1.5%). Discontinuations due to hyperkalemia or abnormal renal function were less than 1.0% in both groups.

Hypertension

INSPRA has been evaluated for safety in 3091 patients treated for hypertension. A total of 690 patients were treated for over 6 months and 106 patients were treated for over 1 year.

In placebo-controlled studies, the overall rates of adverse events were 47% with INSPRA and 45% with placebo. Adverse events occurred at a similar rate regardless of age, gender, or race. Therapy was discontinued due to an adverse event in 3% of patients treated with INSPRA and 3% of patients given placebo. The most common reasons for discontinuation of INSPRA were headache, dizziness, angina pectoris/MI, and increased GGT.

Gynecomastia and abnormal vaginal bleeding were reported with INSPRA but not with placebo. The rates increased with increasing duration of therapy.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of INSPRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin: angioneurotic edema, rash

Clinical Laboratory Test Findings

Heart Failure Post-Myocardial Infarction

Creatinine

Increases of more than 0.5 mg/dL were reported for 6.5% of patients administered INSPRA and for 4.9% of placebo-treated patients.

Potassium

In EPHESUS, the frequencies of patients with changes in potassium (<3.5 mEq/L or >5.5 mEq/L or ≥6.0 mEq/L) receiving INSPRA compared with placebo are displayed in Table 1.

Table 1: Hypokalemia (<3.5 mEq/L) or Hyperkalemia (>5.5 or ≥6.0 mEq/L) in EPHESUS

Rates of hyperkalemia increased with decreasing renal function.

Table 2: Rates of Hyperkalemia ( >5.5 mEq/L) in EPHESUS by Baseline Creatinine Clearance*

The rates of hyperkalemia in EPHESUS in the INSPRA treated group vs. placebo were increased in patients with proteinuria (16% vs 11%), diabetes (18% vs. 13%) or both (26% vs. 16%).

Hypertension

Potassium

In placebo-controlled fixed-dose studies, the mean increases in serum potassium were dose-related and are shown in Table 4 along with the frequencies of values >5.5 mEq/L.

Table 3: Increases in Serum Potassium in the Placebo-Controlled, Fixed-Dose Hypertension Studies of INSPRA