INSPRA- eplerenone tablet, film coated

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

EPLERENONE (UNII: 6995V82D0B) (EPLERENONE - UNII:6995V82D0B)

Tilgjengelig fra:

Pfizer Laboratories Div Pfizer Inc

INN (International Name):

EPLERENONE

Sammensetning:

EPLERENONE 25 mg

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

INSPRA is indicated to improve survival of stable patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI). INSPRA is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (CV) events, primarily strokes and MI. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. Control of high blood pressure should be part of comprehensive CV risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce CV morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent CV outcome benefit has been a reduction in the risk of stroke, but reductions in MI and CV mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased CV risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. INSPRA may be used alone or in combination with other antihypertensive agents. For All Patients INSPRA is contraindicated in all patients with: For Patients Treated for Hypertension INSPRA is contraindicated for the treatment of hypertension in patients with: Risk Summary The available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes (see Clinical Considerations). In animal studies, no adverse developmental effects were observed when eplerenone was administered to pregnant rats and rabbits during organogenesis at exposures 32 and 31 times, respectively the human exposure at the 100 mg/day therapeutic dose. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Pregnant women with heart failure are at increased risk for preterm birth. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Closely monitor pregnant patients for destabilization of their heart failure. Data Animal Data 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) administered during organogenesis. No teratogenic effects were seen in rats or rabbits, although decreased rat fetal weights were observed, and decreased body weight in maternal rabbits and increased rabbit fetal resorptions and post-implantation loss were observed at the highest administered dosages. In a pre- and postnatal development study pregnant rats were administered eplerenone at doses up to 1000 mg/kg/day from Gestation Day 6 through Lactation Day 20. Decreased pup weights were observed beginning at birth at 1000 mg/kg/day. Risk Summary There are no human data available on whether eplerenone is present in human milk, or has effects on breastfed infants or on milk production. Eplerenone was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Infertility Based on animal data, use of INSPRA may compromise male fertility. In mature rats, male fertility was decreased with eplerenone exposure at 17 times the 100 mg/day human therapeutic dose. Reversibility of effects was not evaluated [see Nonclinical Toxicology (13.1)]. In a 10-week study of 304 hypertensive pediatric patients age 4 to 16 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 (age range 5 to 17 years), 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. 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 (14.1)]. 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 (5.1)]. 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, however due to age-related decreases in creatine clearance, the risk of hyperkalemia may be increased [see Warnings and Precautions (5.1)] .

Produkt oppsummering:

INSPRA Tablets are yellow, diamond biconvex, and film-coated. They are debossed with Pfizer on one side. They are supplied as follows: 25 mg NSR 25 1710-01 1710-02 1710-03 50 mg NSR 50 1720-03 1720-01 NA Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [See USP Controlled Room Temperature].

Autorisasjon status:

New Drug Application

Preparatomtale

INSPRA- EPLERENONE TABLET, FILM COATED
PFIZER LABORATORIES DIV PFIZER INC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
INSPRA SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR INSPRA.
INSPRA (EPLERENONE) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2002
INDICATIONS AND USAGE
INSPRA is an aldosterone antagonist indicated for:
Improving survival of stable patients with symptomatic heart failure
with reduced ejection fraction
(HFrEF) after an acute myocardial infarction. (1.1)
The treatment of hypertension, to lower blood pressure. Lowering blood
pressure reduces the risk of
fatal and nonfatal cardiovascular events, primarily strokes and
myocardial infarctions. (1.2)
DOSAGE AND ADMINISTRATION
_HFrEF Post-MI_: Initiate treatment with 25 mg once daily. Titrate to
maximum of 50 mg once daily within 4
weeks, as tolerated. Dose adjustments may be required based on
potassium levels. (2.1)
_Hypertension_: 50 mg once daily, alone or combined with other
antihypertensive agents. For inadequate
response, increase to 50 mg twice daily. Higher dosages are not
recommended. (2.2)
_For all patients:_
Measure serum potassium before starting INSPRA and periodically
thereafter. (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: 25 mg, 50 mg (3)
CONTRAINDICATIONS
_For all patients:_
Serum potassium >5.5 mEq/L at initiation (4)
Creatinine clearance ≤30 mL/min (4)
Concomitant use with strong CYP3A inhibitors (4, 7.1)
_For the treatment of hypertension:_
Type 2 diabetes with microalbuminuria (4)
Serum creatinine >2.0 mg/dL in males, >1.8 mg/dL in females (4)
Creatinine clearance <50 mL/min (4)
Concomitant use of potassium supplements or potassium-sparing
diuretics (4)
WARNINGS AND PRECAUTIONS
Hyperkalemia: Patients with decreased renal function, diabetes,
proteinuria or patients who are taking
ACEs and ARBs, NSAIDs or moderate CYP3A inhibitors are at increased
risk. Monitor serum potassium
levels and adjust dose as needed. (5.1)
ADVERSE REACTIONS
_HFrEF Post-MI_: Mo