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Hyperkalemia: The principal risk of EPLERENONA PENTAFARMA TABLETS (eplerenone) is hyperkalemia. Hyperkalemia, if not recognized in a timely manner, can cause serious, sometimes fatal, arrhythmias. All patients prescribed EPLERENONA PENTAFARMA TABLETS must have their serum potassium level measured before initiating EPLERENONA PENTAFARMA TABLETS therapy, within one week and at one month after the first dose or after a dose adjustment, and measured periodically thereafter, as clinically warranted (see Dosage & Administration).
Hyperkalemia can be minimized by appropriate patient selection, avoidance of certain concomitant treatments, thoroughly informing the patient and periodic monitoring until the effect of EPLERENONA PENTAFARMA TABLETS has been established.
For patient selection and medications which should not be prescribed concomitantly with EPLERENONA PENTAFARMA TABLETS or prescribed with caution, see Contraindications, Interactions, and Adverse Reactions.
EPLERENONA PENTAFARMA TABLETS should not be administered to heart failure patients with initial serum potassium >5.0 mmol/L, and/or eGFR <30 mL/min/1.73 m2. The incidence of hyperkalemia increases with declining renal function (see Tables 6 and 9 in Adverse Reactions).
Diabetic patients with heart failure (HF) who are treated with EPLERENONA PENTAFARMA TABLETS, especially those with proteinuria or renal impairment, should also be treated with caution as they have an increased risk of hyperkalemia. Patients with either diabetes or renal impairment/proteinuria also have an increased risk of hyperkalemia, however the incidence remains lower than in patients with both of these comorbidities (see Tables 7 and 10 in Adverse Reactions).
Impaired Hepatic Function: In 16 subjects with mild-to-moderate hepatic impairment (Child-Pugh Class B) who received 400 mg of eplerenone, no elevations of serum potassium above 5.5 mmol/L were observed. Cmax was not significantly changed but AUC was increased by 42% and eplerenone clearance 30% lower compared to matched controls. The dose recommended is 8 times smaller and, therefore, no dose adjustment is necessary in patients with mild to moderate hepatic impairment.
The use of EPLERENONA PENTAFARMA TABLETS in patients with severe hepatic impairment has not been evaluated and therefore, EPLERENONA PENTAFARMA TABLETS is contraindicated in these patients (see Contraindications, Dosage & Administration, and Pharmacology: Pharmacokinetics: Special Populations and Conditions under Actions).
Impaired Renal Function: See Hyperkalemia as previously mentioned, Contraindications, and Adverse Reactions.
Carcinogenesis, Mutagenesis: Preclinical studies of safety pharmacology, genotoxicity, carcinogenic potential and toxicity to reproduction revealed no special hazard for humans.
In repeat dose toxicity studies, prostate atrophy was observed in rats and dogs at exposure levels several-fold above clinical exposure levels. The prostatic changes were not associated with adverse functional consequences. The clinical relevance of these findings is unknown.
Studies in rats and rabbits showed no teratogenic effects, although decreased body weight in maternal rabbits and increased rabbit fetal resorptions and post-implantation loss were observed at the highest administered dosage.
Use in Pregnancy: See Pregnant Women under Use in Pregnancy & Lactation.
Use in Lactation: See Nursing Women under Use in Pregnancy & Lactation.
Use in Children: The safety and effectiveness of EPLERENONA PENTAFARMA TABLETS have not been established in pediatric patients and EPLERENONA PENTAFARMA TABLETS is not recommended in this patient population.
Use in the Elderly: There were 1641 (46%) patients treated with eplerenone who were 65 and over, while 616 (18.6%) were 75 and over. Patients greater than 75 years did not appear to benefit from the use of eplerenone.
There were 1854 (68%) patients treated with eplerenone in EMPHASIS-HF who were 65 years and over, while 657 (24%) were 75 years and over. Both subgroups of patients appeared to benefit from the use of eplerenone compared to placebo-treated patients, based on the results from the primary endpoint (composite endpoint CV mortality or hospitalization for heart failure) but these results were driven by a significant reduction of hospitalization for heart failure. While hospitalization for heart failure was reduced in all age groups, the study did not show a reduction in cardiovascular mortality with eplerenone in patients 75 years and older.
No initial dose adjustment is required in the elderly. Due to an age-related decline in renal function, the risk of hyperkalemia is increased in elderly patients. This risk may be further increased when co-morbidity associated with increased systemic exposure is also present, in particular mild-to-moderate hepatic impairment. Periodic monitoring of serum potassium is recommended.
