Inspra
Generic: EPLERENONE
Basic Information
Manufacturer
Viatris Specialty LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
1a52bedc-8e2c-4116-a296-a87770676b4a
Indications & Usage
1 INDICATIONS AND USAGE INSPRA is an aldosterone antagonist indicated for: • Improving survival of stable adult patients with symptomatic heart failure with reduced ejection fraction (HFrEF) after an acute myocardial infarction.
( 1.1 ) • The treatment of hypertension in adults, to lower blood pressure.
Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
( 1.2 ) 1.1 Heart Failure Post-Myocardial Infarction INSPRA is indicated to improve survival of stable adult patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI).
1.2 Hypertension INSPRA is indicated for the treatment of hypertension in adults, 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.
( 1.1 ) • The treatment of hypertension in adults, to lower blood pressure.
Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
( 1.2 ) 1.1 Heart Failure Post-Myocardial Infarction INSPRA is indicated to improve survival of stable adult patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI).
1.2 Hypertension INSPRA is indicated for the treatment of hypertension in adults, 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.
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Hyperkalemia [see Warnings and Precautions (5.1) ] HFrEF Post-MI: Most common adverse reactions (>2% and more frequent than with placebo): hyperkalemia and increased creatinine.
( 6.1 ) Hypertension: In clinical studies, adverse reactions with INSPRA were uncommon.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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.
6.2 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: angioedema, rash 6.3 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 [see Clinical Studies (14.1) ] , 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 2.
Table 2.
Hypokalemia (<3.5 mEq/L) or Hyperkalemia (>5.5 or ≥6.0 mEq/L) in EPHESUS Potassium (mEq/L) INSPRA (N=3251) n (%) Placebo (N=3237) n (%) <3.5 273 (8.4) 424 (13.1) >5.5 508 (15.6) 363 (11.2) ≥6.0 180 (5.5) 126 (3.9) Rates of hyperkalemia increased with decreasing renal function.
Table 3.
Rates of Hyperkalemia (>5.5 mEq/L) in EPHESUS by Baseline Creatinine Clearance* * Estimated using the Cockroft-Gault formula.
Baseline Creatinine Clearance INSPRA (N=508) n (%) Placebo (N=363) n (%) ≤30 mL/min 160 (32) 82 (23) 31-50 mL/min 122 (24) 46 (13) 51-70 mL/min 86 (17) 48 (13) >70 mL/min 56 (11) 32 (9) 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 4.
Increases in Serum Potassium in the Placebo-Controlled, Fixed-Dose Hypertension Studies of INSPRA Mean Increase mEq/L % >5.5 mEq/L Daily Dosage n Placebo 194 0 1 25 97 0.08 0 50 245 0.14 0 100 193 0.09 1
( 6.1 ) Hypertension: In clinical studies, adverse reactions with INSPRA were uncommon.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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.
6.2 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: angioedema, rash 6.3 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 [see Clinical Studies (14.1) ] , 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 2.
Table 2.
Hypokalemia (<3.5 mEq/L) or Hyperkalemia (>5.5 or ≥6.0 mEq/L) in EPHESUS Potassium (mEq/L) INSPRA (N=3251) n (%) Placebo (N=3237) n (%) <3.5 273 (8.4) 424 (13.1) >5.5 508 (15.6) 363 (11.2) ≥6.0 180 (5.5) 126 (3.9) Rates of hyperkalemia increased with decreasing renal function.
Table 3.
Rates of Hyperkalemia (>5.5 mEq/L) in EPHESUS by Baseline Creatinine Clearance* * Estimated using the Cockroft-Gault formula.
Baseline Creatinine Clearance INSPRA (N=508) n (%) Placebo (N=363) n (%) ≤30 mL/min 160 (32) 82 (23) 31-50 mL/min 122 (24) 46 (13) 51-70 mL/min 86 (17) 48 (13) >70 mL/min 56 (11) 32 (9) 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 4.
Increases in Serum Potassium in the Placebo-Controlled, Fixed-Dose Hypertension Studies of INSPRA Mean Increase mEq/L % >5.5 mEq/L Daily Dosage n Placebo 194 0 1 25 97 0.08 0 50 245 0.14 0 100 193 0.09 1