Inspra pills 50mg №30

INSPRA

Release form

coated tablets

Active ingredient

Packaging

30 pieces

Indications

- myocardial infarction: in addition to standard therapy, in order to reduce the risk of cardiovascular mortality and morbidity in patients with stable left ventricular dysfunction (ejection fraction <40%) and clinical signs of heart failure after myocardial infarction;

- chronic heart failure: in addition to standard therapy, in order to reduce the risk of cardiovascular mortality and morbidity in patients with chronic heart failure of the II functional class according to the NYHA classification, with left ventricular dysfunction (ejection fraction <35%).

Dosage and administration

The drug is prescribed inside.

Food intake does not affect the absorption of the drug INSPRA ^®. For individual selection of the dose can be applied dosages of 25 and 50 mg.

Myocardial infarction

Treatment should begin with a dose of 25 mg 1 time / day and increase it to 50 mg 1 time / day for 4 weeks, taking into account the concentration of potassium in the blood serum (see table). The recommended maintenance dose of the drug is 50 mg 1 time / day.

Chronic heart failure, starting from the II functional class according to the NYHA classification

Treatment should also begin with a dose of 25 mg 1 time / day and increase it to 50 mg 1 time / day after 4 weeks, taking into account the concentration of potassium in the blood serum (see table).

The maximum daily dose is 50 mg. After a temporary cessation of the drug due to an increase in the content of potassium in the blood serum to 6 mmol / l or more, drug therapy can be resumed at a dose of 25 mg every other day when the content of potassium in the blood serum is <5 mmol / l.

General recommendations

The content of potassium in the serum should be determined before the appointment of the drug Inspra^®during the first week and 1 month after the start of therapy or when changing the dose of the drug. In the future, it is also necessary to periodically monitor the content of potassium in the serum.

Selection of the dose after the start of treatment

Correction of the initial dose in elderly patients not required. Due to the age-related decline in kidney function in elderly patients, the risk of hyperkalemia increases, especially in the presence of comorbidities that increase serum levels of eplerenone, in particular, in violation of liver function from mild to moderate severity. It is recommended to periodically determine the content of potassium in the blood serum (see Table 1, as well as the sections "Special Instructions", "With Caution").

Correction of the initial dose in patients with mild renal impairment not required. The degree of hyperkalemia increases with the deterioration of renal function. It is recommended to periodically determine the content of potassium in the blood serum (see Table 1, as well as the section "Special Instructions"). Drug Inspra^® not removed during hemodialysis. In patients with CHF II FC according to the NYHA classification and impaired renal function of moderate severity (CC 30-60 ml / min), therapy should be started with a dose of 25 mg every other day, followed by dose adjustment depending on the content of potassium in the blood serum (see Table.one).

Have patients with severe renal failure (CC <30 ml / min) use of the drug is contraindicated (see section "Contraindications"). Experience use of the drug Inspra^® in patients with heart failure after myocardial infarction and CC <50 ml / min no. It should be used with caution drug Inspra^® in such patients (see section "With caution"). In patients with QA <50 ml / min, use of the drug Inspra^® at a dose higher than 25 mg 1 time / day has not been studied (also see the section "Special Instructions").

Correction of the initial dose in patients with impaired liver function from mild to moderate severity not required. Considering the increase in the concentration of eplerenone in such patients, it is recommended to regularly monitor the content of potassium in the blood serum, especially in elderly patients (see the section "Special Instructions"). Use of the drug Inspra^® at patients with severely impaired liver function contraindicated (see section "Contraindications").

Concomitant therapy

With the simultaneous use of drugs that have a weak or moderately pronounced inhibitory effect on the CYP3A4 isoenzyme, for example, Erythromycin, saquinavir, Amiodarone, diltiazem, Verapamil and Fluconazole, treatment with Inspra^® You can start with a dose of 25 mg 1 time / day, while the dose of the latter should not exceed 25 mg 1 time / day (see the section "Interaction with other drugs").

Adverse effects

The following are undesirable effects that could be associated with treatment, as well as serious adverse events, the frequency of which is comparable to the incidence of adverse and serious adverse events in the placebo group. Adverse events are distributed by body systems and frequency: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); frequency unknown (cannot be calculated from available data).

From the hemopoietic system: infrequently - eosinophilia.

Metabolism and nutrition disorders: often - hyperkalemia, dehydration, hypercholesterolemia, hypertriglyceridemia; infrequently - hyponatremia, hypothyroidism.

Psychological: infrequently - insomnia.

Nervous system: often - dizziness, fainting; infrequently - headache, hypesthesia.

Cardiovascular: often - myocardial infarction, pronounced decrease in blood pressure; infrequently - atrial fibrillation, left ventricular failure, tachycardia, orthostatic hypotension, thrombosis of the arteries of the lower extremities.

Respiratory: often cough; infrequently - pharyngitis.

Gastrointestinal: often - diarrhea, nausea, constipation; infrequently - flatulence, vomiting.

Liver and biliary tract: infrequently - cholecystitis.

From the skin and subcutaneous fat: often - itching; infrequently - increased sweating, rash; frequency is unknown - angioedema.

Musculoskeletal system: often - cramps in the calf muscles of the legs, musculoskeletal pain; infrequently - back pain.

Urogenital: often - impaired renal function.

Other: infrequently - pyelonephritis, gynecomastia, asthenia, malaise.

Laboratory values: infrequently - an increase in the concentration of residual nitrogen of urea, creatinine, a decrease in the expression of the epidermal growth factor receptor, an increase in the concentration of glucose in the blood serum.

Contraindications

- clinically significant hyperkalemia;

- serum potassium concentration at the beginning of treatment> 5 mmol / l;

- moderate or severe renal failure (CC <50 ml / min in patients after myocardial infarction and with chronic heart failure and CC <30 ml / min in patients with chronic heart failure starting from functional class II);

- plasma creatinine concentration> 2 mg / dL (or> 177 mmol / l) in men or> 1.8 mg / dL (or> 159 mmol / l) in women;

- severe liver failure (Child-Pugh class C);

- simultaneous use of potassium-sparing diuretics, potassium preparations or powerful CYP3A4 inhibitors, for example, itraconazole, Ketoconazole, ritonavir, nelfinavir, Clarithromycin, telithromycin and nefazodone;

- rare inherited diseases such as galactose intolerance, lapp lactase deficiency and glucose-galactose malabsorption syndrome;

- there is no experience of using the drug in children and adolescents under the age of 18, therefore its administration to patients of this age group is not recommended;

- Hypersensitivity to eplerenone or other components of the drug.

WITH caution: type 2 diabetes and microalbuminuria; simultaneous use of eplerenone, ACE inhibitors or angiotensin II receptor antagonists, drugs containing lithium, cyclosporine or tacrolimus, Digoxin and Warfarin in doses close to the maximum therapeutic; elderly age; renal dysfunction (CC less than 50 ml / min).

Use during pregnancy and lactation

Information about the use of the drug in pregnant women do not. The drug should be prescribed with caution and only in cases where the expected benefit to the mother far exceeds the possible risk to the fetus / child.

Information about the removal of eplerenone after ingestion with breast milk is not. The possible undesirable effects of eplerenone on breastfed infants are unknown, so it is advisable either to stop breastfeeding or to cancel the drug, depending on its importance to the mother.

Application for violations of the liver

Correction of the initial dose in patients with impaired liver function from mild to moderate severity not required.

Use of the drug Inspra^® at patients with severely impaired liver function (class C on the Child-Pugh scale) is contraindicated.

Application for violations of kidney function

Correction of the initial dose in patients with mild renal impairment not required. The degree of hyperkalemia increases with the deterioration of renal function. It is recommended to periodically determine the content of potassium in the serum.

In patients with CHF II FC according to the NYHA classification and impaired renal function of moderate severity (CC 30-60 ml / min), therapy should be started with a dose of 25 mg every other day, followed by dose adjustment depending on the serum potassium content.

WITHcaution: renal dysfunction (CC <50 ml / min).

Have patients with severe renal failure (CC <30 ml / min) use of the drug is contraindicated.

Use in children

There is no experience of using the drug in children and adolescents under the age of 18, therefore its administration to patients of this age group is not recommended.

Use in elderly patients

Correction of the starting dose inelderly patients not required. Due to the age-related decline in renal function in elderly patients, the risk of hyperkalemia increases, especially in the presence of comorbidities that increase serum levels of eplerenone, in particular, in violation of liver function from mild to moderate severity. It is recommended to periodically determine the concentration of potassium in the serum.

special instructions

Hyperkalemia

In the treatment of drug Inspra^® hyperkalemia may develop, which is due to its mechanism of action. At the beginning of treatment and when changing the dose of the drug in all patients should be monitored the content of potassium in the serum. In the future, periodic monitoring of the potassium content is recommended for patients with an increased risk of hyperkalemia, for example, the elderly, patients with renal insufficiency (see the section “Dosage and administration”) and diabetes. Given the increased risk of hyperkalemia, the prescription of potassium drugs after the start of treatment with eplerenone is not recommended. Inspra dose reduction^® leads to a decrease in the content of potassium in the serum. In one study, the addition of hydrochlorothiazide to eplerenone prevented an increase in serum potassium.

Renal dysfunction

In patients with impaired renal function, incl.diabetic microalbuminuria, it is recommended to regularly monitor the content of potassium in the serum. The risk of developing hyperkalemia increases with a decrease in renal function. Although the number of patients with type 2 diabetes and microalbuminuria was limited in research, nevertheless, an increase in the frequency of hyperkalemia was noted in this small sample (see the section “With Care”). In this regard, such patients should be treated with caution. Drug Inspra^® not removed during hemodialysis. Use of the drug Inspra^® contraindicated in severe renal failure (see "Contraindications").

Liver dysfunction

In patients with mild or moderate liver dysfunction (5-6 and 7-9 points according to Child-Pugh classification), no increase in serum potassium levels greater than 5.5 mmol / l was detected. In such patients, the concentration of electrolytes should be monitored. In patients with severely impaired liver function, eplerenone has not been studied, therefore its use is contraindicated (see section "Contraindications").

Inductors of isoenzyme CYP3A4

Simultaneous use of the drug Inspra^® with strong inducers of an isoenzyme CYP3A4 is not recommended (see the section "Interaction with Other Medicines").

Cyclosporine, tacrolimus, preparations containing lithium

During treatment with the drug Inspra^® the use of these agents should be avoided (see section "Interaction with other drugs").

Lactose

Inspra drug tablets^® contain lactose, so they should not be prescribed to patients with rare hereditary diseases, such as lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Influence on ability to drive motor transport and control mechanisms

Effects of Inspra^® The ability to drive or use the equipment has not been studied. However, given the possibility of the drug to cause dizziness and fainting, caution should be exercised when driving or using technology while taking the drug Inspra^®.

Overdose

Cases of overdose of eplerenone in humans have not been described. The most likely manifestations of overdose may be a decrease in blood pressure and hyperkalemia.

Treatment: with an excessive decrease in blood pressure, supportive treatment should be prescribed. In the case of the development of hyperkalemia, standard therapy is indicated. Eplerenone is not removed by hemodialysis. It is established that eplerenone is actively associated with Activated carbon.

Drug interaction

Pharmacodynamic interaction

Potassium-sparing diuretics and potassium preparations: Considering the increased risk of hyperkalemia, eplerenone should not be prescribed to patients receiving potassium-sparing diuretics and potassium preparations (see section "Contraindications"). Potassium-sparing diuretics can enhance the effects of antihypertensive drugs and other diuretics.

Preparations containing lithium: The interaction of eplerenone with lithium preparations has not been studied. However, in patients who received lithium preparations in combination with diuretics and ACE inhibitors, cases of increasing the concentration and intoxication with lithium are described. If such a combination is necessary, it is advisable to control the concentration of lithium in the blood plasma (see section "Special Instructions").

Cyclosporin, tacrolpmus: cyclosporine and tacrolimus can cause renal dysfunction and increase the risk of hyperkalemia. The simultaneous use of eplerenone and cyclosporine or tacrolimus should be avoided. If during treatment with eplerenone, cyclosporine or tacrolimus is required, it is recommended to carefully monitor serum potassium and kidney function (see "Special Instructions").

Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAID treatment can lead to acute renal failure due to direct suppression of glomerular filtration, especially in patients at risk (elderly patients and / or patients with dehydration). With the joint use of these funds before and during treatment, it is necessary to provide an adequate water regime and monitor kidney function.

Trimethoprim: simultaneous use of trimethoprim with eplerenone increases the risk of hyperkalemia. It is recommended to control serum potassium and kidney function, especially in patients with renal insufficiency and in elderly patients.

ACE inhibitors and angiotensin II receptor antagonists: When using eplerenone with ACE inhibitors or angiotensin II receptor antagonists, the content of serum potassium should be carefully monitored.Such a combination may lead to an increased risk of hyperkalemia, especially in patients with impaired renal function, including in elderly patients. Do not use a triple combination of an ACE inhibitor and angiotensin II receptor antagonists with eplerenone.

Alpha₁-blockers (prazosin, alfuzosin): with simultaneous use of alpha₁-adrenergic blockers with eplerenone may increase the antihypertensive effect and / or increase the risk of orthostatic hypotension, and therefore, control of blood pressure is recommended, especially when changing body position.

Tricyclic antidepressants, neuroleptics, amifostine, Baclofen : with the simultaneous use of these agents with eplerenone, the antihypertensive effect may increase or the risk of orthostatic hypotension may increase.

Glucocorticoids, tetracosactide: the simultaneous use of these agents with eplerenone can lead to sodium and fluid retention.

Pharmacokinetic interaction

In vitro studies indicate that eplerenone does not inhibit CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 isoenzymes. Eplerenone is not a substrate or inhibitor of glycoprotein R.

Digoxin: AUC of digoxin when used simultaneously with eplerenone is increased by 16% (90% CI: 4% -30%). Care must be taken if digoxin is used in doses close to the maximum therapeutic.

Warfarin: clinically significant pharmacokinetic interaction with warfarin was not detected. Care must be taken if warfarin is applied in doses close to the maximum therapeutic.

Substrates of isoenzyme CYP3A4: In special studies, no signs of pharmacokinetic interaction of eplerenone with CYP3A4 isoenzyme substrates, for example, midazolam and cisapride, were identified.

Inhibitors of isoenzyme CYP3A4

Strong inhibitors of isoenzyme CYP3A4: with the use of eplerenone with CYP3A4 isoenzyme inhibiting agents, a significant pharmacokinetic interaction is possible. A strong inhibitor of the isoenzyme CYP3A4 (ketoconazole 200 mg 2 times / day) caused an increase in the AUC of eplerenone by 441%. The simultaneous use of eplerenone with strong inhibitors of CYP3A4 isoenzyme, such as ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazadone, is contraindicated (see section "Contraindications").

Weak and moderate inhibitors of CYP3A4 isoenzyme: simultaneous use with erythromycin, saquinavir, amiodarone, diltiazem, verapamil and fluconazole was accompanied by significant pharmacokinetic interaction (the degree of increase in AUC varied from 98% to 187%). With the simultaneous use of these agents with eplerenone, the dose of the latter should not exceed 25 mg (see section "Dosage and administration").

Inductors of isoenzyme CYP3A4

The simultaneous administration of preparations containing St. John's wort (St John's Wort, a strong inducer of the CYP3A4 isoenzyme) with eplerenone caused a 30% decrease in the AUC of the latter. When using stronger CYP3A4 isoenzyme inducers, such as rifampicin, a more pronounced decrease in the AUC of eplerenone is possible. Given the possible reduction in eplerenone efficacy, the simultaneous use of strong inducers of the CYP3A4 isoenzyme (rifampicin, Carbamazepine, phenytoin, phenobarbital, preparations containing St. John's wort) is not recommended (see the section "Special Instructions").

Antacids: Based on a pharmacokinetic clinical study, a significant interaction of antacids with eplerenone with their simultaneous use is not expected.

Pharmacy sales terms

The drug is available on prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not higher than 30 ° C.