Inspra

Name: Inspra

Pharmacology

Mechanism of Action

Selective aldosterone receptor antagonist; blocks aldosterone binding at the mineralocorticoid receptor

Pharmacokinetics

Half-Life: 3.5-6 hr

Peak Plasma Time: 1-2 hr

Bioavailability: 69%

Protein Bound: 50%

Vd: 43-90 L

Metabolism: primarily hepatic CYP3A4

Metabolite: no active mets identified

Total Body Clearance: 10 L/hr

Excretion: feces (32%) and urine (67%)

What special dietary instructions should I follow?

Talk to your doctor about drinking grapefruit juice while taking this medicine.

Do not use salt substitutes containing potassium while you are taking eplerenone. If your doctor prescribes a low-salt or low-sodium diet, follow these directions carefully.

US Brand Name

  1. Inspra

Side effects

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

  • Hyperkalemia [see WARNINGS AND PRECAUTIONS]

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.

Congestive 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

Congestive 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], 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*

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)
* Estimated using the Cockroft-Gault formula.

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

Daily Dosage n Mean Increase mEq/L % > 5.5 mEq/L
Placebo 194 0 1
25 97 0.08 0
50 245 0.14 0
100 193 0.09 1

Read the entire FDA prescribing information for Inspra (Eplerenone)

Read More »

Inspra Overview

Inspra is a prescription medication used to treat high blood pressure. Inspra belongs to a group of drugs called mineralocorticoid receptor blockers. These work by blocking the action of aldosterone, a natural substance in the body that raises blood pressure.

This medication comes in tablet form and is taken once or twice a day, with or without food.

Common side effects of Inspra include diarrhea, coughing, fatigue, and hedache. Inspra can also cause dizziness. Do not drive or operate heavy machinery until you know how Inspra affects you.

Side Effects of Inspra

Serious side effects have been reported with Inspra. See the "Inspra Precautions" section.

Common side effects of Inspra include:

  • diarrhea
  • coughing
  • fatigue
  • dizziness
  • flu-like symptoms
  • increased potassium levels

This is not a complete list of Inspra side effects.Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088.

Inform MD

Before taking Inspra, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to Inspra or to any of its ingredients
  • have or have had high blood levels of potassium
  • have diabetes
  • have gout
  • have liver disease
  • have kidney disease
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamines, and herbal supplements.

Inspra and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Inspra crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Inspra.

Inspra Overdose

If you take too much Inspra, call your healthcare provider or local Poison Control Center or seek emergency medical attention right away.

If Inspra is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

What should I avoid while taking Inspra (eplerenone)?

Do not use potassium supplements or salt substitutes while you are taking eplerenone, unless your doctor has told you to.

Interactions for Inspra

Metabolized by CYP3A4 isoenzyme.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered plasma eplerenone concentrations) with drugs that induce or inhibit CYP3A4.1

Does not inhibit or induce the CYP isoenzymes 1A2, 3A4, 2C19, 2C9, or 2D6, suggesting that the drug is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.1 21

Specific Drugs and Food1

Drug or Food

Interaction

Comments

ACE inhibitors

Possible increased serum potassium concentrations, hyperkalemia

Amiloride

Increased risk for hyperkalemia

Concomitant use contraindicated in patients with hypertension

Amiodarone

Pharmacokinetic interaction unlikely

Amlodipine

Pharmacokinetic interaction unlikely

Angiotensin II receptor antagonists

Possible increased serum potassium concentrations, hyperkalemia

Antacids (e.g., aluminum- and magnesium-containing)

Pharmacokinetic interaction unlikely

Astemizole

Pharmacokinetic interaction unlikely

Chlorzoxazone

Pharmacokinetic interaction unlikely

Cisapride

Pharmacokinetic interaction unlikely

Clarithromycin

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Cyclosporine

Pharmacokinetic interaction unlikely

Dexamethasone

Pharmacokinetic interaction unlikely

Dextromethorphan

Pharmacokinetic interaction unlikely

Diclofenac

Pharmacokinetic interaction unlikely

Digoxin

Pharmacokinetic interaction unlikely

Erythromycin

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

Ethinyl estradiol

Pharmacokinetic interaction unlikely

Fluconazole

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

Fluoxetine

Pharmacokinetic interaction unlikely

Glyburide

Pharmacokinetic interaction unlikely

Grapefruit juice

Increased eplerenone exposure

Hormonal contraceptives (norethindrone/ethinyl estradiol)

Pharmacokinetic interaction unlikely

Itraconazole

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Ketoconazole

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Lithium

Possible increased serum lithium concentrations resulting in lithium toxicity;1 such interaction observed with concomitant administration of diuretics and/or ACE inhibitors and lithium1 5 7 14 15

If used concomitantly, frequently monitor serum lithium concentrations1

Losartan

Pharmacokinetic interaction unlikely

Lovastatin

Pharmacokinetic interaction unlikely

Midazolam

Pharmacokinetic interaction unlikely

Mephobarbital

Pharmacokinetic interaction unlikely

Methylphenidate

Pharmacokinetic interaction unlikely

Methylprednisolone

Pharmacokinetic interaction unlikely

Metoprolol

Pharmacokinetic interaction unlikely

Nefazodone

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Nelfinavir

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Nifedipine

Pharmacokinetic interaction unlikely

NSAIAs

Possible decreased antihypertensive effect and/or severe hyperkalemia in patients with impaired renal function

Phenytoin

Pharmacokinetic interaction unlikely

Potassium-sparing agents or potassium supplements

Possible increased risk of hyperkalemia 1 4 21

Ritonavir

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Saquinavir

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

St. John's wort

Decreased eplerenone AUC

Simvastatin

Pharmacokinetic interaction unlikely

Spironolactone

Increased risk for hyperkalemia

Concomitant use contraindicated in patients with hypertension

Tolbutamide

Pharmacokinetic interaction unlikely

Triamterene

Increased risk for hyperkalemia

Concomitant use contraindicated in patients with hypertension

Triazolam

Pharmacokinetic interaction unlikely

Troleandomycin

Increased plasma concentrations of eplerenone

Concomitant use contraindicated

Verapamil

Increased plasma concentrations of eplerenone

Reduce eplerenone dosage (see Dosage: Hypertension, under Dosage and Administration)

Warfarin

Pharmacokinetic interaction unlikely

Inspra Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common
  • Excess of cholesterol in the blood
  • excess of triglycerides in the blood
Incidence not known
  • Abdominal or stomach pain
  • arm, back, or jaw pain
  • chest pain or discomfort
  • chest tightness or heaviness
  • confusion
  • difficulty with breathing
  • dizziness
  • fast or irregular heartbeat
  • headache
  • irregular heartbeat
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • nausea
  • nervousness
  • numbness or tingling in the hands, feet, or lips
  • pain or discomfort in the arms, jaw, back, or neck
  • rash
  • shortness of breath
  • sweating
  • vomiting
  • weakness or heaviness of the legs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common
  • Abnormal vaginal bleeding
  • breast pain
  • chills
  • cloudy urine
  • cough
  • diarrhea
  • fever
  • general feeling of discomfort or illness
  • joint pain
  • loss of appetite
  • muscle aches and pains
  • swelling of the breasts or breast soreness in both females and males
  • unusual tiredness or weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses of Inspra

  • It is used to treat high blood pressure.
  • It is used to help heart function after a heart attack.
  • It may be given to you for other reasons. Talk with the doctor.

Inspra Dosage and Administration

Congestive Heart Failure Post-Myocardial Infarction

Initiate treatment at 25 mg once daily and titrate to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient.

Once treatment with Inspra has begun, adjust the dose based on the serum potassium level as shown in Table 1.

Table 1. Dose Adjustment in Congestive Heart Failure Post-MI
Serum Potassium (mEq/L) Dose Adjustment
<5.0 25 mg every other day to 25 mg once daily
25 mg once daily to 50 mg once daily
5.0–5.4 No adjustment
5.5–5.9 50 mg once daily to 25 mg once daily
25 mg once daily to 25 mg every other day
25 mg every other day to withhold
≥6.0 Withhold and restart at 25 mg every other day when potassium levels fall to <5.5 mEq/L

Hypertension

The recommended starting dose of Inspra is 50 mg administered once daily. The full therapeutic effect of Inspra is apparent within 4 weeks. For patients with an inadequate blood pressure response to 50 mg once daily increase the dosage of Inspra to 50 mg twice daily. Higher dosages of Inspra are not recommended because they have no greater effect on blood pressure than 100 mg and are associated with an increased risk of hyperkalemia [see Clinical Studies (14.2)].

Recommended Monitoring

Measure serum potassium before initiating Inspra therapy, within the first week, and at one month after the start of treatment or dose adjustment. Assess serum potassium periodically thereafter.

Check serum potassium and serum creatinine within 3–7 days of a patient initating a moderate CYP3A inhibitor ACE inhibitors, angiotensin-II blockers or non-steroidal-anti-inflammatories.

Dose Modification for Use with Moderate CYP3A Inhibitors

In post-MI CHF patients receiving a moderate CYP3A inhibitor (e.g., erythromycin, saquinavir, verapamil, and fluconazole), do not exceed 25 mg once daily. In patients with hypertension receiving a moderate CYP3A inhibitor, initiate at 25 mg once daily. For inadequate blood pressure response, dosing may be increased to a maximum of 25 mg twice daily [see Drug Interactions (7.1)].

PRINCIPAL DISPLAY PANEL - 25 mg Tablet Blister Pack

Inspra®
(eplerenone)
tablets

25 mg

G.D. Searle LLC
Division of Pfizer Inc,
NY, NY 10017

EXP & LOT AREA

PRINCIPAL DISPLAY PANEL - 50 mg Tablet Bottle Label

NDC 0025-1720-03

Pfizer

Inspra®
(eplerenone) tablets

50 mg

30 Tablets
Rx only

Inspra 
eplerenone tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0025-1710
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
EPLERENONE (EPLERENONE) EPLERENONE 25 mg
Inactive Ingredients
Ingredient Name Strength
LACTOSE, UNSPECIFIED FORM  
MICROCRYSTALLINE CELLULOSE  
CROSCARMELLOSE SODIUM  
HYPROMELLOSE, UNSPECIFIED  
SODIUM LAURYL SULFATE  
TALC  
MAGNESIUM STEARATE  
TITANIUM DIOXIDE  
POLYETHYLENE GLYCOL, UNSPECIFIED  
POLYSORBATE 80  
FERRIC OXIDE YELLOW  
FERRIC OXIDE RED  
Product Characteristics
Color YELLOW Score no score
Shape DIAMOND (biconvex) Size 7mm
Flavor Imprint Code Pfizer;NSR;25
Contains     
Packaging
# Item Code Package Description
1 NDC:0025-1710-01 30 TABLET, FILM COATED in 1 BOTTLE
2 NDC:0025-1710-02 90 TABLET, FILM COATED in 1 BOTTLE
3 NDC:0025-1710-03 100 BLISTER PACK in 1 BOX, UNIT-DOSE
3 1 TABLET, FILM COATED in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021437 09/27/2002
Inspra 
eplerenone tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0025-1720
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
EPLERENONE (EPLERENONE) EPLERENONE 50 mg
Inactive Ingredients
Ingredient Name Strength
LACTOSE, UNSPECIFIED FORM  
MICROCRYSTALLINE CELLULOSE  
CROSCARMELLOSE SODIUM  
HYPROMELLOSE, UNSPECIFIED  
SODIUM LAURYL SULFATE  
TALC  
MAGNESIUM STEARATE  
TITANIUM DIOXIDE  
POLYETHYLENE GLYCOL, UNSPECIFIED  
POLYSORBATE 80  
FERRIC OXIDE YELLOW  
FERRIC OXIDE RED  
Product Characteristics
Color YELLOW Score no score
Shape DIAMOND (biconvex) Size 9mm
Flavor Imprint Code Pfizer;NSR;50
Contains     
Packaging
# Item Code Package Description
1 NDC:0025-1720-03 30 TABLET, FILM COATED in 1 BOTTLE
2 NDC:0025-1720-01 90 TABLET, FILM COATED in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021437 09/27/2002
Labeler - G.D. Searle LLC Division of Pfizer Inc (829077085)
Registrant - Pfizer Inc (113480771)
Establishment
Name Address ID/FEI Operations
NEOLPHARMA, INC. 078709787 PACK(0025-1710, 0025-1720)
Establishment
Name Address ID/FEI Operations
Pfizer Pharmaceuticals LLC 829084552 ANALYSIS(0025-1720, 0025-1710), LABEL(0025-1720, 0025-1710), MANUFACTURE(0025-1720, 0025-1710), PACK(0025-1720, 0025-1710)
Establishment
Name Address ID/FEI Operations
Pharmacia and Upjohn Company LLC 618054084 API MANUFACTURE(0025-1710, 0025-1720)
Revised: 04/2017   G.D. Searle LLC Division of Pfizer Inc
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