Zimvastin E is a cholesterol lowering agent based on Simvastatin and Ezetimibe. Simvastatin is a cholesterol lowering agent, a synthetic derivative of a fermentation product from Aspergillus terreus. Once orally absorbed, simvastatin, which is an inactive lactose, is transformed by hydrolysis into the corresponding B-hydroxy acid. The latter is a major metabolite and an inhibitor of 3-hydroxymethylglutaryl coenzyme A (HGM-CoA) reductase, an enzyme that catalyzes an early and speed limiting step in cholesterol biosynthesis. As a result, simvastatin reduces plasma concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol. In addition, simvastatin moderately increases high-density lipoprotein (HDL) cholesterol and lowers plasma triglycerides.
Orally administered simvastatin has a high selectivity for the liver, where it reaches higher concentrations than in other tissues. Simvastatin undergoes considerable first-pass extraction from the liver, its primary point of action, with subsequent excretion of the drug into the bile. In man, the systemic exposure to the active form of simvastatin has been found to be less than 5% of the orally administered dose, and 95% of that portion binds to plasma proteins.
Ezetimibe belongs to a new class of lipid lowering compounds that selectively inhibit intestinal absorption of cholesterol and related plant sterols, it is active and potent orally with a unique mechanism of action, different from other classes of reducing compounds of cholesterol.
Ezetimibe is located on the brush border of the small intestine and inhibits cholesterol absorption, leading to a reduction in the contribution of cholesterol to the liver, a reduction in the deposition of liver cholesterol and an increase in the clearance of cholesterol from the blood. Ezetimibe does not increase the excretion of bile acid (such as bile acid sequestrants), nor does it inhibit the synthesis of cholesterol in the liver (such as statins).
After oral administration, Ezetimibe is rapidly absorbed and extensively transformed by conjugation into a phenolic glucuronide with pharmacological activity (ezetimibe glucuronide). Ezetimibe glucuronide achieves on average peak plasma concentrations (Cmax) in one to two hours, and ezetimibe in four to twelve hours. Both forms are slowly removed from plasma, with indications of significant enterohepatic recycling.
The combination of a statin (Simvastatin) and Ezetimibe is indicated, (along with a specific diet and exercise) to reduce high total cholesterol (total-C), low-density lipoprotein (LDL-C) cholesterol, apolipoprotein B (Apo B), non-HDL cholesterol, triglycerides (TG) and to increase HDL cholesterol in patients with primary hypercholesterolemia (heterozygous familial and non-familial); as well as mixed dyslipidemia, as adjunctive therapy to the diet for the treatment of patients with high triglyceride levels.
Liver function tests are recommended for all patients before starting treatment and periodically for the first year (every six months) or one year after the last dose adjustment. Attention should be paid to those with increased serum transaminases; In the latter, transaminase measurements should be repeated soon after and more frequently during treatment. If transaminases continue to increase, particularly if they reach three times the upper limit of their normal values and the increase is persistent, the administration of the drug should be discontinued. Zimvastin-E should be used with caution in patients who have unexplained increases in transaminases with contraindications to the use of simvastatin.
Successive increases in transaminases (triple or more than the upper limit of their normal values) have been observed in patients on ezetimibe and a statin. Because the effects of increased exposure to Ezetimibe in patients with moderate or severe hepatic impairment are unknown, treatment with Ezetimibe is not recommended.
When Ezetimibe is co-administered with an HMG-CoA reductase inhibitor, liver function tests should be performed at the start of therapy and in accordance with the recommendations of the HMG-CoA reductase inhibitor.
Skeletal muscle: No increase in myopathy or rhabdomyolysis associated with Ezetimibe was demonstrated in clinical trials compared to placebo or an HMG-CoA reductase inhibitor alone. However, caution should be exercised because myopathy and rhabdomyolysis are known to be adverse reactions to HMG-CoA reductase inhibitors and other lipid-lowering drugs.
Use in children: Until now, the use of simvastatin in children is not recommended. Based on total ezetimibe, no pharmacokinetic data are available in children younger than 10 years.
- Potent CYP3A4 inhibitors (Itraconazole, Ketoconazole, Erythromycin, Clarithromycin) are contraindicated with ezetimibe – simvastatin.
- Fibrates, cyclosporine, amiodarone, verapamil, diltiazen.
- Antacid, cholesterol, anticoagulants and coumarins.
The association of simvastatin with ezetimibe in doses of 10/10 mg to 80/10 mg is generally well tolerated. The most frequently reported adverse reactions with the association are: asthenia, arthralgia, myalgia, dizziness and headaches. The most frequently reported adverse reactions in patients treated with ezetimibe associated with other statins are: upper respiratory infection, headache, myalgia, low back pain, sinusitis, abdominal pain, arthralgia, fatigue, diarrhea, vertigo, chest pain. The incidence of transaminase increases is slightly higher in patients treated with ezetimibe associated with a statin than with the statin alone.
The patient must be on a cholesterol-lowering diet. The recommended starting dose is Zimvastin E 10/20 mg once daily at night with or without food. In patients who need to lower LDL-C more than 55%, zimvastin E 10/40 mg can be started once a day at night. The lipid concentrations are then measured after two or more weeks and the dosage adjusted if necessary. In patients with homozygous familial hypercholesterolemia the recommended dose is zimvastin E 10/40 mg once daily at night. These dosages are subject to medical judgment.
Delicate medicine, use only under medical prescription.
Zimvastin E – 10/20
Each coated tablet contains:
C.S.P. excipients 1 coated tablet
Zimvastin E – 10/40
Each coated tablet contains:
C.S.P. excipients 1 coated tablet
Zimvastin E – 10/20: Box containing two blisters with 20 tablets each.
Zimvastin E – 10/40: Box containing two blisters with 20 tablets each.
Keep in a cool place (below 30 ° C). Protect it from light and moisture.
Zimvastin E is contraindicated in patients with recognized hypersensitivity to any of the components of this medicine or to other statins. Do not administer to patients with active liver disease, chronic alcoholism or with elevated liver enzyme values of unknown origin. Pregnancy: Zimvastin-E is contraindicated during pregnancy. Zimvastin-E should be administered to women of childbearing potential only when pregnancy is highly unlikely and after appropriate information has been given about potential risks to the fetus. If the patient becomes pregnant, treatment should be discontinued immediately. Lactation: Zimvastin-E is contraindicated during lactation. Since a small amount of statins is excreted in milk and adverse reactions in the infant are possible, women under treatment with Zimvastin-E should not breastfeed their children.