Inegy pills 10mg + 20mg №28

Indications and usage

- primary hypercholesterolemia: heterozygous (familial and non-familial) hypercholesterolemia or mixed hyperlipidemia (as a supplement to a diet to reduce total cholesterol, LDL, apolipoprotein B, TG, low density lipoproteins, to increase HDL);

- homozygous familial hypercholesterolemia: to reduce elevated levels of total cholesterol and LDL (both as an additional treatment to other lipid-lowering therapy, for example, LDL-apheresis, and in its absence).

Before initiating therapy with Inegy, patients should switch to a cholesterol-lowering diet and follow it throughout the entire course of treatment.

The drug is administered orally 1 time / day, in the evening, regardless of the meal.

The dose depends on the initial level of LDL, the goal of treatment and the therapeutic effect and can vary from 10/10 mg (10 mg of ezetimibe + 10 mg of simvastatin) to 10/80 mg (10 mg of ezetimibe + 80 mg of simvastatin) per day. An initial dose of 10/20 mg (10 mg of ezetimibe + 20 mg of simvastatin) per day is usually recommended.

In order to gradually reduce the level of LDL, a dose of the drug of 10/10 mg can be recommended (10 mg of ezetimibe + 10 mg of simvastatin).

For a significant reduction in LDL (more than 55%), patients may be recommended an initial dose of 10/40 mg (10 mg of ezetimibe + 40 mg of simvastatin) per day.

2 weeks after the start of treatment, as well as throughout the course of treatment, lipid levels should be monitored and, if necessary, the dose of the drug should be adjusted.

Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia, mixed dyslipidemia)

Inegy is recommended to be taken daily in a dose of 10/40 mg (10 mg of ezetimibe + 40 mg of simvastatin) or 10/80 mg (10 mg of ezetimibe + 80 mg of simvastatin) in the evening.

Therapy should always be carried out against the backdrop of a cholesterol-lowering diet.

To further reduce levels of TG and non-HDL and increase HDL in patients with mixed dyslipidemia, treatment with Inegy can be supplemented with fenofibrate.

Homozygous familial hypercholesterolemia

Inegy is recommended to be taken in a dose of 10/40 mg or 10/80 mg 1 time / day in the evening. The drug should be used in combination with another lipid-lowering therapy (for example, LDL-apheresis). In the absence of the possibility of additional treatment, Inegy can be prescribed as monotherapy.

Elderly patients dose adjustment is not required.

Patients with mild liver failure (5-6 points on the Child-Pugh scale) dose adjustment is not required. It is not recommended to prescribe the drug. patients with moderate (7–9 points on the Child-Pugh scale) or severe (more than 9 points on the Child-Pugh scale) liver failure.

Patients with mild to moderate renal failure dose adjustment is not required. At severe renal failure (CC <30 ml / min) the drug in a dose of more than 10/10 mg / day should be used with caution.

Use in combination with other drugs.

Inegy should be taken at least 2 hours before or 4 hours after taking bile acids.

For patients receiving nicotinic acid in a dose of more than 1 g / day, cyclosporine or danazol, the maximum dose of Inegy is 10/10 mg / day.

For patients receiving Amiodarone or Verapamil, the maximum dose of Inegy is 10/20 mg / day.

Adverse reactions

The safety of the drug Inegy has been studied in clinical studies involving more than 3,800 patients and during post-marketing surveillance in different countries. In general, Inegy is well tolerated by patients.

The side effects of taking Inegy are comparable to the side effects previously reported when taking ezetimibe and / or Simvastatin.

According to placebo-controlled studies and in the period of post-marketing follow-up in patients who took Inedzhi, the following characteristic side effects were noted with a frequency of> 1/100 and <1/10, both with and without a well-defined connection:

Gastrointestinal: flatulence, abdominal pain, constipation, diarrhea, dyspepsia, vomiting, cholelithiasis, cholecystitis, jaundice, hepatitis; rarely (> 1/10 000, <1/1000) - nausea; very rarely (<1/1 000) - pancreatitis; in some cases - liver failure.According to controlled combined clinical studies, a clinically significant increase in serum transaminases (ALT and / or ACT 3 times or more) was observed in 1.7% of patients who received Inegy (these changes were asymptomatic, did not lead to cholestasis and passed on their own when discontinuing or continuing treatment).

From the hemopoietic system: thrombocytopenia, anemia.

From the musculoskeletal system: myalgia, arthralgia; very rarely - myopathy / rhabdomyolysis.

From the side of the central nervous system: dizziness, headache.

Allergic reactions: rarely (> 1/10 000, <1/1000) - skin rash and urticaria; very rarely (<1/10 000) - Anaphylactic reactions and angioedema.

Other: fatigue, asthenia. In 0.2% of patients who received Inegy, there was a clinically significant increase in CPK (10 times or more VGN).

Contraindications

- liver disease in the active phase or a persistent increase in the activity of hepatic transaminases of unknown etiology;

- moderate and severe degree of liver failure (7 or more points on the Child-Pugh scale);

- pregnancy;

- lactation period (breastfeeding);

- age up to 18 years;

- hypersensitivity to the drug.

WITH caution the drug should be used in cases of severe renal failure (CC <30 ml / min), alcohol abuse, a history of liver diseases, muscle soreness or changes in skeletal muscle tone of unknown etiology, gall bladder diseases, while Inegy is administered with fibrates.

Pregnancy and Breastfeeding

The drug is contraindicated in pregnancy and lactation (breastfeeding).

Special notes

If it is necessary to administer Inegy to patients with severe renal insufficiency (CC <30 ml / min), the drug at a dose of more than 10/10 mg / day should be used with caution.

Inegy should be used with caution in patients taking large amounts of alcohol and / or having a history of liver disease. Acute liver diseases or an inexplicably sustained high level of liver enzyme activity are contraindications to taking the drug. Inegy is not recommended for patients with moderate or severe liver failure.

Patients with a history of history require careful monitoring during treatment with Inegy. A few days before large surgical interventions and in the early postoperative period, it is recommended to stop taking the drug temporarily.

Simvastatin, like other inhibitors of HMG-CoA reductase, can cause myopathy, manifested by muscle pain, weakness, fatigue, and also an increase in the level of CPK more than 10 times relative to VGN. Sometimes myopathy takes the form of rhabdomyolysis and may be accompanied by myoglobinuria, acute renal failure, and in rare cases with a fatal outcome. The risk of myopathy is increased due to an increase in the blood plasma inhibitory activity against HMG-CoA reductase.The decision to administer the drug to Inegy in combination with other drugs should be taken individually, taking into account the possible risk of myopathy.

Most cases of rhabdomyolysis during treatment with simvastatin were combined with a burdened history, including renal failure, predominantly diabetic. Patients with a history of history require careful monitoring during treatment with Inegy.

The risk of myopathy / rhabdomyolysis depends on the dose of simvastatin. In clinical studies, when patients were carefully monitored, myopathy / rhabdomyolysis was observed: while taking simvastatin at a dose of 20 mg in approximately 0.03% of cases, at a dose of 40 mg in 0.08%, at a dose of 80 mg in 0.4% of cases.

At the beginning of the reception or with an increase in the dose of the drug Inegy patients should be warned about the risk of myopathy and the need to immediately inform the doctor about the occurrence of unexplained muscle pain, weakness or indisposition. In case of diagnosis or suspicion of myopathy, therapy with Inegy should be immediately discontinued. The presence of these symptoms and / or an increase in the level of CPK more than 10 times higher than VGN, means the development of myopathy. In most cases, when discontinuing simvastatin, the symptoms of myopathy and elevated CPK levels disappeared.

At the beginning of receiving or increasing the dose of Inegy, periodic control of the CPK level may be required, however, this measure does not guarantee the prevention of myopathy.

Influence on ability to drive motor transport and control mechanisms

No studies have been conducted to assess the effect of the drug on the ability to drive and to other potentially dangerous activities. However, there is no reason to assume that Inegy can somehow influence these processes.

Several cases of simvastatin overdose have been reported with no clinically relevant consequences for patients; the maximum dose taken was 3.6 g.

In clinical studies, 15 healthy patients who took ezetimibe at a dose of 50 mg / day for 14 days, and 18 patients with primary hypercholesterolemia who took ezetimibe at a dose of 40 mg / day for 56 days, showed good tolerability of therapy. Several cases of overdose have been reported in which undesirable effects were either not observed or were not serious.

Treatment: there is no antidote to ezetimibu and simvastatin. In case of an overdose of the drug Inegy, it is recommended to carry out symptomatic and supportive treatment.

When using Inegy, especially in high doses, in combination with powerful inhibitors of CYP3A4, for example, with itraconazole, Ketoconazole, Erythromycin, Clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, the risk of myopathy / rhabdomyolysis increases. If you need therapy with itraconazole, ketoconazal, erythromycin,clarithromycin or telithromycin Inegy should be discontinued. Strong inhibitors of the isoenzyme CYP3A4 increase the risk of myopathy, because prevent the removal of simvastatin. Concurrent use of the drug with other drugs containing strong CYP3A4 inhibitors should be avoided, unless the expected benefits of the combination therapy exceed the potential risk.

With the simultaneous use of Inegy and fenofibrate or gemfibrozil, the concentration of ezetimibe in blood plasma increases by 1.5 and 1.7 times, respectively; however, this increase is not clinically significant. The safety and efficacy of Inegy in combination with fibrates (with the exception of fenofibrate) are not well understood. In the study, which was attended by 184 patients who took Inegy at a dose of 10/20 mg / day and fenofibrate at a dose of 160 mg for 12 weeks, no adverse reactions were observed from the gallbladder. It is assumed that fibrates can increase the secretion of cholesterol in bile, which in turn can lead to cholelithiasis.

With simultaneous use of the drug Inegy, especially in high doses, with cyclosporine, danazol or nicotinic acid (more than 1 g / day) increases the risk of myopathy / rhabdomyolysis. Inegy in combination with nicotinic acid (more than 1 g / day) should be administered with caution, since nicotinic acid as a monotherapy can cause myopathy.For patients taking cyclosporine or danazol in a dose of more than 1 g / day, the dose of Inegy should not exceed 10/10 mg / day. The potential benefit and potential risk should be assessed when Inegy is prescribed for patients receiving cyclosporine or danazol. When prescribing Inegy in combination with cyclosporine, constant monitoring of the concentration of cyclosporine in the blood is necessary.

With simultaneous use with Inegy, especially in high doses, with amiodarone or verapamil increases the risk of myopathy / rhabdomyolysis. There is evidence of the development of myopathy in 6% of patients who participated in relevant clinical studies and received simvastatin at a dose of 80 mg and amiodarone. For patients taking amiodarone or verapamil, the dose of Inegy should not exceed 10/20 mg / day. The combined use of Inegy in doses exceeding 10/20 mg / day with amiodarone or verapamil should be avoided, unless the advantages of combined therapy exceed the potential risk of myopathy.

In patients receiving fusidic acid at the same time as Inegy, the risk of myopathy may increase, so these patients need clinical control.

In patients receiving diltiazem and Inegy at a dose of 10/80 mg, the risk of myopathy increases slightly. Clinical studies have shown that the risk of myopathy is the same for patients taking simvastatin at a dose of 40 mg with or without diltiazem concomitant therapy.

Preclinical studies have shown that ezetimibe does not induce a CYP3A4 isoenzyme. There was no clinically significant pharmacokinetic interaction between ezetimibe and other drugs that are metabolic substrates involving isoenzymes of the cytochrome P450 system 1A2, 2D6, 2C8, 2C9, and 3A4 or N-acetyltransferase. Simvastatin is metabolized by CYP3A4 isoenzyme, but does not possess CYP3A4 inhibitory activity, therefore its effect on the plasma concentration of other drugs metabolized by CYP3A4 is unlikely.

When combined with Kolestiramine, the average AUC of total ezetimibe (ezetimibe and ezetimibe glucuronide) decreased by approximately 55%. With the combined use of Inegy and Kolestiramine, the increasing decrease in LDL can be less pronounced.

In 2 clinical studies (one in healthy volunteers, the other in patients with hypercholesterolemia) simvastatin at a dose of 20-40 mg / day moderately potentiated the effect of coumarin anticoagulants, extending the prothrombin time when the initial value of MHO (the ratio of the patient's prothrombin time to the prothrombin time is normal blood plasma) equal to 1.7 in healthy volunteers increased to 1.8, and in patients with hypercholesterolemia, the initial value of 2.6 increased to 3.4. Patients taking coumarin anticoagulants are carefully monitored for blood coagulation parameters (prothrombin time) before the first ingestion of Inegy.Subsequent measurements should be regular to achieve stable indicators of MHO, then measurements are carried out at the usual intervals recommended for control in the treatment with coumarin anticoagulants. With the abolition of the drug and changing the dose Inegy spend an extraordinary determination of the parameters of blood clotting. In patients not taking anticoagulants, simvastatin therapy did not cause bleeding or changes in blood clotting parameters.

At the same time taking Inegy and antacids, the level of absorption of ezetimibe is slightly reduced, while its bioavailability does not change.

Grapefruit juice contains one or more components that inhibit the CYP3A4 isoenzyme, and may increase the level of substances metabolized by this isoenzyme in the blood plasma. The effect of drinking juice in small amounts (250 ml per day) is minimal (the activity inhibiting HMG-CoA reductase increases in plasma by 13%, as shown by the AUC value) and has no clinical significance. However, the use of large amounts of juice (more than 1 l per day) while taking simvastatin significantly increases the level of activity in the blood plasma that inhibits HMG-CoA reductase. Therefore, you should avoid eating large amounts of grapefruit juice and at the same time taking the drug.

The drug is available on prescription.

List B.The drug should be stored out of reach of children at a temperature not exceeding 30 ° C.