Inspra tabs 50mg #30

Inspra instruction

You can buy Inspra here

Inspra is a potassium-sparing diuretic drug.

Release form and composition

Dosage form - film-coated tablets: diamond-shaped, yellow, on one side there is an inscription Pfizer, on the other - an inscription NSR above the number indicating the dosage, "25" or "50" (14 pcs. In blisters, in a cardboard box with first opening control 2 blisters; 10 pcs. in blisters, in a cardboard box with first opening control 2, 3, 5, 10 or 20 blisters and instructions for use of Inspra).
Compound:
    active ingredient: eplerenone - 25 mg or 50 mg in 1 tablet;
    excipients: croscarmellose sodium, hypromellose, microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate, talc, lactose monohydrate;
    film sheath: Opadry yellow YS-1-12524-A (titanium dioxide, polysorbate-80, hypromellose, macrogol, iron dye red oxide, iron dye yellow oxide).

Pharmacodynamics

The active substance of the drug - eplerenone, is characterized by high selectivity in relation to mineralocorticoid receptors in humans. It interferes with the binding of these receptors to aldosterone, the main hormone of the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and is involved in the pathogenesis of diseases of the cardiovascular system.
The drug promotes a persistent increase in serum aldosterone and plasma renin activity. Renin secretion is subsequently suppressed by aldosterone through a feedback mechanism, but an increase in circulating aldosterone concentration and renin activity does not affect the effect of eplerenone.
Eplerenone was studied in the double-blind, placebo-controlled Eplerenone Postacute Myocardial Infarction Heart Failure Efficacy and SUrvival Study (EPHESUS), which enrolled 6632 patients with clinical signs of heart failure, acute myocardial infarction and left ventricular dysfunction (ejection fraction <40%) ... For 3-14 days after acute myocardial infarction, in addition to standard basic therapy, patients received eplerenone or placebo. The initial dose was 25 mg once a day, by the end of 4 weeks it increased to 50 mg once a day, provided that the concentration of potassium in the blood serum did not exceed 5.0 mmol / L. Standard therapy included acetylsalicylic acid, beta-blockers, loop diuretics, nitrates, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) inhibitors, or angiotensin converting enzyme (ACE) inhibitors.
The primary point of the study was total mortality, the combined point was mortality or hospitalization due to cardiovascular disease. Compared with placebo, eplerenone therapy reduced the risk of all-cause mortality by 15%, mainly due to a decrease in mortality due to cardiovascular diseases. The risk of death / hospitalization due to cardiovascular disease with eplerenone was reduced by 13%. The decrease in the absolute risk for the two points studied was 2.3% and 3.3%, respectively.
In studies of the dynamics of the electrocardiogram in healthy volunteers, no significant effect of eplerenone on heart rate, duration of QT, PR, QRS intervals was found.
The clinical study Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure (EMPHASIS-HF) for ~ 21 months involved 2,737 patients under the age of 75 years who were diagnosed with chronic heart failure of functional class II (CHF II FC) according to the classification New York Heart Association (NYHA) and severe systolic dysfunction. Patients received beta-blockers, angiotensin II receptor blockers, or ACE inhibitors prior to starting active eplerenone. The main focus of the study was death from cardiovascular disease or hospitalization due to heart failure. According to the results of studies in patients with CHF II FC, who received eplerenone at an average dose of 25-50 mg per day, mortality decreased by 37%. The effectiveness of the drug in the elderly (over 75 years old) has not been studied.

Pharmacokinetics

After oral administration of 100 mg of eplerenone, the absolute bioavailability of the substance is 69%. Its absorption does not depend on the regimen and diet. The maximum concentration (Cmax) in blood plasma is observed after 2 hours. Cmax and area under the concentration-time curve (AUC) depend: linearly on dose ≤ 100 mg, non-linearly on dose> 100 mg. The equilibrium state is reached within 2 days.
The connection with blood plasma proteins (mainly with the alpha-1-acid group of glycoproteins) is approximately 50%. The substance does not bind to erythrocytes. In an equilibrium state, the calculated volume of distribution is 50 (± 7) liters.
Eplerenone is metabolized mainly with the participation of the isoenzyme CYP3A4. Active metabolites have not been identified.
After a single oral administration of labeled eplerenone, about 67% of the dose taken is excreted through the kidneys, about 32% through the intestines, with no more than 5% unchanged. The half-life is 3-5 hours. Plasma clearance is approximately 10 l / h.
The pharmacokinetics of eplerenone at a daily dose of 100 mg has been studied in men, women and elderly patients over 65 years of age. Pharmacokinetics did not differ significantly in men and women. Cmax and AUC in elderly patients were 22% and 45% higher, respectively, than in patients aged 18 to 45 years.
In patients with severe renal insufficiency, Cmax and AUC are higher, respectively, by 24% and 38% compared with patients in the control group. In patients on hemodialysis, these parameters were lower by 3% and 26%, respectively. No correlation was found between plasma clearance of eplerenone and creatinine clearance. Eplerenone is not cleared by hemodialysis.
Compared with healthy volunteers, in patients with moderate hepatic impairment (7-9 points according to the Child-Pugh classification), the equilibrium AUC and Cmax when taking eplerenone at a dose of 400 mg are higher by 42% and 3.6%, respectively. The pharmacokinetics of eplerenone in patients with severe hepatic impairment has not been studied, so the drug is not prescribed for this category of patients.
When studying the pharmacokinetics of eplerenone prescribed in a daily dose of 50 mg in patients with heart failure of II – IV functional class, it was found that the equilibrium AUC and Cmax were 38% and 30% higher, respectively, than in healthy volunteers matched by sex, age and body weight. The clearance rate of eplerenone in patients with heart failure is similar to that in healthy older adults.

Indications for use

According to the instructions, Inspra is used in addition to the standard therapy for the following diseases / conditions:
    myocardial infarction - to reduce the risk of mortality and morbidity in patients with clinical signs of heart failure after myocardial infarction and patients with stable left ventricular dysfunction (ejection fraction <40%);
    chronic heart failure - in order to reduce the risk of mortality and morbidity in patients with CHF II FC, with left ventricular dysfunction (ejection fraction <35%).

Contraindications for Inspra

Absolute:
    age under 18;
    simultaneous use of potassium-sparing diuretics, potassium preparations or potent inhibitors of the CYP3A4 isoenzyme, such as itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, nefazodone;
    lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
    severe liver failure (more than 9 points on the Child-Pugh scale);
    renal failure of moderate or severe degree (creatinine clearance <30 ml / min) in patients with CHF II FC;
    serum potassium at the start of treatment> 5.0 mmol / l;
    clinically significant hyperkalemia;
    hypersensitivity to the drug.
The triple combination of eplerenone with angiotensin II receptor antagonists and an ACE inhibitor should not be used.
Relative (requiring caution):
    elderly age;
    simultaneous use of warfarin and digoxin in doses close to the maximum therapeutic, tacrolimus, cyclosporine, lithium preparations, ACE inhibitors, strong inducers of the CYP3A4 isoenzyme, angiotensin II receptor antagonists;
    renal dysfunction (creatinine clearance less than 50 ml / min);
    microalbuminuria and type 2 diabetes mellitus.

Instructions for use of Inspra: method and dosage

The coated tablets are taken orally once a day. Eating food does not affect the effectiveness of Inspra.
The initial dose is 25 mg, after 4 weeks the daily dosage is increased to 50 mg in 1 dose (under the control of serum potassium levels).
The maintenance dose for myocardial infarction is usually 50 mg once a day.
In chronic heart failure II FC according to NYHA classification after temporary discontinuation of Inspra due to an increase in serum potassium ≥ 6 mmol / L, therapy can be resumed after the serum potassium level reaches <5 mmol / L, the dose of the drug should be 25 mg, taken 1 time per day every other day.
With the combined use of drugs with a weak or moderately pronounced inhibitory effect on the CYP3A4 isoenzyme (for example, verapamil, amiodarone, diltiazem, fluconazole, saquinavir or erythromycin), the dose of Inspra (both initial and maintenance) is 25 mg once a day.
Selection of the dose after the start of treatment, depending on the potassium content in the blood serum:
    <5.0 mmol / l: the dose is increased to 25 mg once a day, if a dose of 25 mg was prescribed every other day; up to 50 mg once a day, if a dose of 25 mg was prescribed once a day;
    5.0–5.4 mmol / l: the dose remains the same;
    5.5–5.9 mmol / l: the dose is reduced to 25 mg once a day, if a dose of 50 mg was prescribed once a day; up to 25 mg every other day, if a dose of 25 mg was prescribed once a day, temporarily cancel the drug if up to 25 mg was prescribed every other day;
    > 6.0 mmol / L: the drug is discontinued.

Side effects of Inspra

Distribution of adverse reactions in frequency: often - from> 1/100 to <1/10; infrequently - from> 1/1000 to <1/100, frequency unknown - from the available data the frequency cannot be calculated.
Possible side effects by system organ class:
    nervous system: often - dizziness, fainting; infrequently - asthenia, malaise, hypesthesia, headache;
    respiratory system: often - cough, infrequently - pharyngitis;
    cardiovascular system: often - a marked decrease in blood pressure, myocardial infarction; infrequently - atrial fibrillation, tachycardia, thrombosis of the arteries of the lower extremities, left ventricular failure, orthostatic hypotension;
    gastrointestinal tract (GIT): often - constipation, diarrhea, nausea; infrequently - flatulence, vomiting;
    kidneys and urinary tract: often - impaired renal function;
    liver and biliary tract: infrequently - cholecystitis;
    hematopoietic system and lymphatic system: infrequently - eosinophilia;
    musculoskeletal system and connective tissue: often - musculoskeletal pain, cramps in the calf muscles; infrequently - back pain;
    skin and subcutaneous fat: often - itching of the skin; infrequently - rash, increased sweating; frequency unknown - angioedema;
    mental disorders: infrequently - insomnia;
    infections: infrequently - gynecomastia, pyelonephritis;
    metabolic and nutritional disorders: often - hypercholesterolemia, hyperkalemia, hypertriglyceridemia, dehydration; infrequently - hypothyroidism, hyponatremia;
    laboratory parameters: infrequently - an increase in serum glucose concentration, a decrease in the expression of the epidermal growth factor receptor, an increase in the concentration of residual urea nitrogen and creatinine.

Overdose

No cases of overdose of eplerenone have been reported. The most likely symptoms are hyperkalemia and a marked drop in blood pressure. With hyperkalemia, standard therapy is recommended, with a decrease in blood pressure, supportive treatment. Hemodialysis is ineffective. Eplerenone actively binds to activated carbon.

Special instructions

Before the start of therapy, during the first week of treatment, one month after the appointment of the drug and then periodically, the potassium content in the blood serum should be determined.
Inspra may contribute to the development of hyperkalemia, which is due to the mechanism of action of eplerenone. In this regard, before prescribing the drug and when changing the dose, it is necessary to control the level of potassium in the blood serum. With continued treatment, monitoring of potassium concentration should be carried out in patients at risk of developing hyperkalemia. These include the elderly, people with diabetes and people with kidney failure. For the same reason, it is not recommended to take potassium supplements after the end of Inspra treatment. Reducing the dose of eplerenone helps to reduce serum potassium. The study found that the simultaneous use of hydrochlorothiazide prevents an increase in serum potassium levels.
In combination with strong inducers of the CYP3A4 isoenzyme, the use of Inspra is not recommended.
You should also avoid the combined use of drugs containing lithium, tacrolimus and cyclosporine.

Influence on the ability to drive vehicles and complex mechanisms

The effect of eplerenone on psychomotor and cognitive functions has not been studied, however, the drug can cause dizziness and fainting, therefore, during therapy, care should be taken when driving and working with possible dangerous consequences.

Application during pregnancy and lactation

There are no data on the safety of using Inspra in pregnant women. The drug can be prescribed only in cases of urgent need, when the expected benefit to the woman significantly outweighs the potential risks to the fetus.
It is not known whether eplerenone is excreted in breast milk, therefore it is necessary to assess the situation individually with a doctor - it is worth interrupting breastfeeding or refraining from prescribing the drug.

Childhood use

There is no experience with eplerenone in patients under 18 years of age. It is not recommended to prescribe the drug for children and adolescents.

With impaired renal function

Severe renal insufficiency (creatinine clearance <30 ml / min) is a contraindication to the use of the drug.
Inspra should be used with caution when treating patients with creatinine clearance <50 ml / min.
Patients with CHF II FC and concomitant renal impairment of moderate severity (creatinine clearance from 30 to 60 ml / minute) should begin treatment with a dose of 25 mg every other day, then the dosage may be adjusted depending on the level of potassium in the blood serum.
For mild renal impairment, dose adjustment is not required. Since the degree of hyperkalemia increases in case of deterioration of the renal condition, it is recommended to monitor the potassium content in the blood serum.

For violations of liver function

Severe liver dysfunctions (class C on the Child-Pugh scale) are a contraindication to the use of Inspra.
Mild to moderate hepatic impairment does not require adjustment of the initial dose of eplerenone.

Use in the elderly

Elderly patients do not need to adjust the initial dose of the drug.
Due to the age-related decline in renal function in the elderly, the risk of developing hyperkalemia increases, especially if there are concomitant diseases that contribute to an increase in the concentration of eplerenone in the blood serum - mild to moderate liver dysfunction. For this reason, periodically during treatment with Inspra, the determination of the concentration of potassium in the blood serum is indicated.

Drug interactions

Pharmacodynamic interactions

    preparations containing lithium: there is a risk of an increase in the concentration of lithium and the development of intoxication. In cases where the simultaneous use of drugs is clinically justified, it is necessary to control the concentration of lithium in the blood plasma;
    nonsteroidal anti-inflammatory drugs: the risk of developing acute renal failure, especially in patients at risk (dehydration, old age). If the simultaneous use of drugs is clinically justified, it is necessary to ensure the control of renal function and an adequate water regime;
    potassium-sparing diuretics and potassium supplements: the risk of hyperkalemia increases (not recommended combination);
    trimethoprim: the risk of developing hyperkalemia increases. If the simultaneous use of drugs is clinically justified, it is necessary to monitor serum potassium and renal function, especially in the elderly and patients with renal insufficiency;
    amifostine, baclofen, antipsychotics, tricyclic antidepressants: the antihypertensive effect may increase and / or the risk of orthostatic hypotension may increase;
    antagonists of angiotensin II receptors, ACE inhibitors: the likelihood of developing hyperkalemia increases, especially in the elderly and patients with impaired renal function, as a result, careful monitoring of the level of potassium in the blood serum is required; a triple combination of eplerenone with an ACE inhibitor and an angiotensin II receptor antagonist should not be used;
    tetracosactide, glucocorticoids: sodium and fluid retention is possible;
    alpha1-adrenergic blockers (alfuzosin, prazosin): the antihypertensive effect may increase, the risk of orthostatic hypotension may increase, for this reason, blood pressure control is indicated, especially when changing body position;
    tacrolimus, cyclosporine: there is a risk of impaired renal function, the likelihood of developing hyperkalemia increases. Such combinations should be avoided whenever possible. If tacrolimus or cyclosporine is required during treatment with Inspra, it is recommended that renal function and serum potassium be closely monitored.

Pharmacokinetic interactions

    warfarin: no clinically significant pharmacokinetic interaction has been identified. Caution should be exercised if warfarin is shown to be used in a dose close to the maximum therapeutic dose;
    digoxin: its AUC increases by 16%. Caution should be exercised if digoxin is shown to be used in a dose close to the maximum therapeutic dose;
    CYP3A4 isoenzyme substrates (for example, midazolam, cisapride): no signs of pharmacokinetic interaction have been identified;
    antacids: significant interaction is not expected;
    inducers of the CYP3A4 isoenzyme: St. John's wort - decreases the AUC of eplerenone by 30%, rifampicin and other stronger inducers - possibly a more pronounced decrease in AUC and the effectiveness of eplerenone (not recommended combination);
    weak and moderate inhibitors of the isoenzyme CYP3A4 (amiodarone, erythromycin, verapamil, fluconazole, diltiazem, saquinavir): the degree of increase in AUC varies from 98% to 187%. If it is necessary to use such a combination, the dose of eplerenone should not exceed 25 mg;
    strong inhibitors of the CYP3A4 isoenzyme (nefazod, telithromycin, clarithromycin, ritonavir, itraconazole, nelfinavir, ketoconazole): a significant pharmacokinetic interaction is possible (contraindicated combinations).
According to in vitro studies, eplerenone does not inhibit isoenzymes CYP2D6, CYP2C19, CYP3A4, CYP2C9, CYP1A2. The substance is not a substrate or an inhibitor of glycoprotein P.

Storage term and conditions

Shelf life is 3 years.
Keep out of the reach of children. Store not exceeding a temperature of 30 ° C.

Reviews about Inspra

Reviews of doctors who prescribe the drug according to indications about Inspra are positive. In patients with chronic heart failure and patients after myocardial infarction, soft tissue edema and congestion decrease, high blood pressure decreases, ventricular diastolic function improves, there is a significant decrease in pre- and afterload on the heart, and the development and progression of left ventricular hypertrophy slows down.

Terms of sell

You can buy Inspra without a prescription.