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Inspra (Eplerenone) - Warnings and Precautions

 
 



WARNINGS AND PRECAUTIONS

Hyperkalemia

Minimize the risk of hyperkalemia with proper patient selection and monitoring, and avoidance of certain concomitant medications [See CONTRAINDICATIONS (4), ADVERSE REACTIONS, and DRUG INTERACTIONS (7) ]. Monitor patients for the development of hyperkalemia until the effect of INSPRA is established. Patients who develop hyperkalemia (>5.5 mEq/L) may continue INSPRA therapy with proper dose adjustment. Dose reduction decreases potassium levels. [See DOSAGE AND ADMINISTRATION.]

The rates of hyperkalemia increase with declining renal function. [See ADVERSE REACTIONS.] Patients with hypertension who have serum creatinine levels >2.0 mg/dL (males) or >1.8 mg/dL (females) or creatinine clearance ≤50 mL/min should not be treated with INSPRA. [See CONTRAINDICTIONS (4).] Patients with CHF post-MI who have serum creatinine levels >2.0 mg/dL (males) or >1.8 mg/dL (females) or creatinine clearance ≤50mL/min should be treated with INSPRA with caution.

Diabetic patients with CHF post-MI should also be treated with caution, especially those with proteinuria. The subset of patients in the EPHESUS study with both diabetes and proteinuria on the baseline urinalysis had increased rates of hyperkalemia compared to patients with either diabetes or proteinuria. [See ADVERSE REACTIONS.]

Impaired Hepatic Function

Mild-to-moderate hepatic impairment did not increase the incidence of hyperkalemia. In 16 subjects with mild-to-moderate hepatic impairment who received 400 mg of eplerenone, no elevations of serum potassium above 5.5 mEq/L were observed. The mean increase in serum potassium was 0.12 mEq/L in patients with hepatic impairment and 0.13 mEq/L in normal controls. The use of INSPRA in patients with severe hepatic impairment has not been evaluated. [See CLINICAL PHARMACOLOGY.]

Impaired Renal Function

Patients with decreased renal function are at increased risk of hyperkalemia. [See CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS.]

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. INSPRA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Teratogenic Effects

Embryo-fetal development studies were conducted with doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits (exposures up to 32 and 31 times the human AUC for the 100 mg/day therapeutic dose, respectively). No teratogenic effects were seen in rats or rabbits, although decreased body weight in maternal rabbits and increased rabbit fetal resorptions and post-implantation loss were observed at the highest administered dosage. Because animal reproduction studies are not always predictive of human response, INSPRA should be used during pregnancy only if clearly needed.

Nursing Mothers

The concentration of eplerenone in human breast milk after oral administration is unknown. However, preclinical data show that eplerenone and/or metabolites are present in rat breast milk (0.85:1 [milk:plasma] AUC ratio) obtained after a single oral dose. Peak concentrations in plasma and milk were obtained from 0.5 to 1 hour after dosing. Rat pups exposed by this route developed normally. Because many drugs are excreted in human milk and because of the unknown potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

In a 10-week study of 304 hypertensive pediatric patients age 4 to 17 years treated with INSPRA up to 100 mg per day, doses that produced exposure similar to that in adults, INSPRA did not lower blood pressure effectively. In this study and in a 1-year pediatric safety study in 149 patients, the incidence of reported adverse events was similar to that of adults.

INSPRA has not been studied in hypertensive patients less than 4 years old because the study in older pediatric patients did not demonstrate effectiveness.

INSPRA has not been studied in pediatric patients with heart failure.

Geriatric Use

Congestive Heart Failure Post-Myocardial Infarction

Of the total number of patients in EPHESUS, 3340 (50%) were 65 and over, while 1326 (20%) were 75 and over. Patients greater than 75 years did not appear to benefit from the use of INSPRA. [See CLINICAL STUDIES.]

No differences in overall incidence of adverse events were observed between elderly and younger patients. However, due to age-related decreases in creatinine clearance, the incidence of laboratory-documented hyperkalemia was increased in patients 65 and older. [See WARNINGS AND PRECAUTIONS.]

Hypertension

Of the total number of subjects in clinical hypertension studies of INSPRA, 1123 (23%) were 65 and over, while 212 (4%) were 75 and over. No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects.

Page last updated: 2009-08-10

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