Pharmacological action Vytorin 10/40 mg:
Vytorin Lipid-lowering agent. Selectively inhibits the absorption of cholesterol (including fitoholesterina) in the intestine (brush border fringes of the small intestine). The mechanism of action different from that of other classes of lipid-lowering drugs (including statins, bile acid sequestrants, fibrates). In contrast, bile acid sequestrants ezetimibe does not increase the excretion of bile acids, in contrast to the statins did not inhibit the synthesis of cholesterol in the liver. When entering the small intestine slows the absorption of cholesterol that leads to a decrease in revenues from its gut to the liver. After 2 weeks reduces the absorption of cholesterol in the intestine by 54% compared with placebo.
Uses Vytorin 10/40 mg:
The primary hypercholesterolemia (heterozygous familial and non-family) as a monotherapy (as an adjunct to diet), in combination therapy with a statin, as an adjunct to diet (in ineffectiveness of statin monotherapy). Homozygous familial hypercholesterolemia: in combination with statins as an adjunct to diet (patients may also receive additional treatment, including LDL apheresis). Homozygous sitosterolemiya: adjuvant therapy to diet.
Contraindications Vytorin 10/40 mg:
Hypersensitivity, acute liver disease or persistent increase in activity of “liver” enzymes, moderate (7-9 points on the scale of Child-Pyuga) and heavy (more than 9 points on the scale of Child-Pyuga) the degree of liver failure. Pregnancy and lactation, age 18 years (effectiveness and safety have not been established). Simultaneous with the appointment of fibrates (at present the efficacy and safety have not been established).
Side effects Vytorin 10/40 mg:
The most frequent (1-10%) monotherapy: headache, abdominal pain, diarrhea. Combination therapy with a statin: headache, fatigue, abdominal pain, constipation, diarrhea, bloating, nausea, myalgia. More than 0.1-1%: allergic reactions, including angioedema and skin rash. In monotherapy the frequency of clinically significant increase in activity of “liver” enzymes (ALT and / or ACT) in three or more times was the same for the drug (0.5%) and placebo (0.3%). In the combined treatment with statins in clinically important increase in activity of “liver” enzymes is 1.3% for patients taking ezetimibe with a statin, and 0.4% for taking only a statin. Increased activity of “liver” enzymes are usually asymptomatic, not accompanied by the formation of stones in the gallbladder and passes as the continuation of treatment and after discontinuation. Clinically significant increase in creatine kinase more than 10 times was comparable in patients receiving the drug as monotherapy or in combination with a statin, as well as in patients receiving placebo or a statin.
Dosage and administration Vytorin 10/40 mg:
Inside, at any time, regardless of the meal. Recommended dose – 10 mg 1 time a day Combination therapy with statins: 10 mg 1 time a day together with statins in compliance with all recommendations for the use of designated statin. Concomitant therapy with a fatty acid sequestrants: 10 mg 1 time a day not later than 2 hours before taking fatty acid sequestrants, or no earlier than 4 h after it. No dose adjustment for elderly patients, as well as in renal failure is not required. Mild hepatic impairment (5-6 points on the scale of Child-Pyuga) dose adjustment is required.
Cautions:
Before treatment, patients should go to the corresponding lipid-lowering diet and continue to observe her during the entire period of drug therapy. In the combined treatment with a statin monitoring of liver function should be carried out at the beginning of treatment, and more – in accordance with the recommendations for the statin. Clinical experience in children and adolescents (ages 9 to 17 years) is limited to patients with homozygous familial hypercholesterolemia and sitosterolemiey.
Interaction Vytorin 10/40 mg:
When concomitantly with drugs metabolized isoenzymes of cytochrome P450 CYP1A2, CYP2D6, CYP2C8, CYP2C9 and CYP3A4, or N-acetyltransferase, a clinically significant pharmacokinetic interactions were observed. It has no effect on the pharmacokinetics of dapsone, dextromethorphan, digoxin, oral contraceptives (ethinyl estradiol and levonorgestrel), glipizide, tolbutamide, midazolam, and warfarin. Simultaneous administration of cimetidine with ezetimibe influence the bioavailability of ezetimibe has not. Simultaneous treatment with antacids reduces the rate of absorption of ezetimibe but has no effect on its bioavailability. Kolestiramin reduces the AUC of total ezetimibe (ezetimibe + ezetimibe glucuronide) at 55%. Safety and efficacy of ezetimibe when used with fibrates is not installed. Fibrates may increase cholesterol release into the bile, leading to cholelithiasis. Simultaneous treatment with fenofibrate or gemfibrozil increases the concentration of total ezetimibe approximately 1.5 and 1.7 times respectively. Despite the fact that this increase is not considered clinically significant, the appointment of ezetimibe with fibrates is not recommended. Atorvastatin, simvastatin, pravastatin, lovastatin, or fluvastatin clinically significant pharmacokinetic changes do not cause ezetimibe. In patients undergoing transplantation the kidney, with the spacecraft more than 50 ml / min, continuously receiving cyclosporine, a single dose of ezetimibe 10 mg was associated with increased 2.3-7.9 times the AUC in ezetemiba. In patients undergoing kidney transplantation, with severe renal insufficiency (creatinine clearance 13.2 mL/min/1.73 m) and receiving combined therapy, including cyclosporine, showed an increase in T1 / 2 of ezetimibe 12 times.
