Eplerenone
Encyclopedia
Eplerenone (icon) is an aldosterone antagonist
used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone
, though it may be more specific for the mineralocorticoid receptor
and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction
. It is marketed by Pfizer
under the trade name Inspra. Eplerenone is a potassium-sparing diuretic
, meaning that it helps the body get rid of water but still keep potassium.
dysfunction within 3–14 days of an acute myocardial infarction
, in combination with standard therapies and as treatment against hypertension. In the EPHESUS trial, this lowered risk by 2.4%, with a risk of death of 16.7% in the placebo arm , giving a relative risk of 0.86 , or a number of patients needed to treat (NNT : Number needed to treat
) of 41 to save one life ( 100% divided by 2.4%) .
C). The manufacturer of eplerenone also contraindicates ( relative C.I. ) concomitant treatment with ketoconazole
, itraconazole
or other potassium-sparing diuretic
s (though the manufacturer still considers taking these drugs to be absolute C.I.) Potential benefits should be weighted against possible risks.
s (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension
, dizziness, altered renal function, and increased creatinine concentration.
enzyme CYP3A4
. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole
and itraconazole
is contraindicated. Other CYP3A4 inhibitors including erythromycin
, saquinavir
, and verapamil
should be used with caution. Other drugs that increase potassium
concentrations may increase the risk of hyperkalaemia associated with eplerenone therapy, including salt substitutes, potassium supplements and other potassium-sparing diuretic
s.
Aldosterone antagonist
Aldosterone antagonist refers to diuretic drugs which antagonize the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure...
used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone
Spironolactone
Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
, though it may be more specific for the mineralocorticoid receptor
Mineralocorticoid receptor
The mineralocorticoid receptor , also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.MR is a receptor with high affinity for mineralocorticoids...
and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
. It is marketed by Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
under the trade name Inspra. Eplerenone is a potassium-sparing diuretic
Potassium-sparing diuretic
Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....
, meaning that it helps the body get rid of water but still keep potassium.
Indications
Eplerenone is specifically indicated for the reduction of risk of cardiovascular death in patients with heart failure and left ventricularLeft ventricle
The left ventricle is one of four chambers in the human heart. It receives oxygenated blood from the left atrium via the mitral valve, and pumps it into the aorta via the aortic valve.-Shape:...
dysfunction within 3–14 days of an acute myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, in combination with standard therapies and as treatment against hypertension. In the EPHESUS trial, this lowered risk by 2.4%, with a risk of death of 16.7% in the placebo arm , giving a relative risk of 0.86 , or a number of patients needed to treat (NNT : Number needed to treat
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
) of 41 to save one life ( 100% divided by 2.4%) .
Contraindications
Eplerenone is contraindicated in patients with hyperkalaemia, severe renal impairment (creatinine Cl less than 30 ml/min), or severe hepatic impairment (Child-Pugh scoreChild-Pugh score
In medicine , the Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis...
C). The manufacturer of eplerenone also contraindicates ( relative C.I. ) concomitant treatment with ketoconazole
Ketoconazole
Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
, itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
or other potassium-sparing diuretic
Potassium-sparing diuretic
Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....
s (though the manufacturer still considers taking these drugs to be absolute C.I.) Potential benefits should be weighted against possible risks.
Adverse effects
Common adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, dizziness, altered renal function, and increased creatinine concentration.
Drug interactions
Eplerenone is primarily metabolised by the cytochrome P450Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
enzyme CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole
Ketoconazole
Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
and itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
is contraindicated. Other CYP3A4 inhibitors including erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
, saquinavir
Saquinavir
Saquinavir is an antiretroviral drug used in HIV therapy. It falls in the protease inhibitor class. Two formulations have been marketed:*a hard-gel capsule formulation of the mesylate, with trade name Invirase, which requires combination with ritonavir to increase the saquinavir bioavailability;*a...
, and verapamil
Verapamil
Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
should be used with caution. Other drugs that increase potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
concentrations may increase the risk of hyperkalaemia associated with eplerenone therapy, including salt substitutes, potassium supplements and other potassium-sparing diuretic
Potassium-sparing diuretic
Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....
s.