Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):VED
АТХ:A.10.B.G Thiazolidinediones
A.10.B.G.02 Rosiglitazone
Pharmacodynamics:Selective binding with peroxisome proliferator-activated receptor γ (PPAR-γ), modulation of transcription of insulin-sensitive genes controlling glucose and lipid metabolism.
Pharmacokinetics:Adsorption is 99%. The time to reach the maximum concentration of 1 hour. Food intake helps to reduce the maximum concentration to 28%, increasing the time it takes to reach 1.75 hours, but this is not considered clinically significant. Relationship with plasma proteins 99.8% (serum albumin). Biotransformation in the liver to inactive metabolites is carried out by N-demethylation, hydroxylation and conjugation with residues of sulfuric and glucuronic acids. In studies in vitro The involvement of CYP2C8 isoenzymes and, to a lesser extent, CYP3C9 in the metabolism of rosiglitazone has been established. Half-life 3-4 hours Elimination by the kidneys (64%) and with feces (23% in the form of metabolites).
Indications:Diabetes mellitus type 2: as a monotherapy with insufficient effectiveness of diet and exercise; in combination with sulfonylurea derivatives,metformin or insulin in order to improve the control of glycemia; in combination with sulfonylurea derivatives and metformin (triple combination therapy) to improve glycemic control.
IV.E10-E14.E11 Non-insulin-dependent diabetes mellitus
Contraindications:Hypersensitivity, type 1 diabetes mellitus (in the absence of insulin is ineffective), moderate or severe hepatic insufficiency, dysmenorrhea, pregnancy, breast-feeding, patients under 18 years of age (efficacy and safety not determined).
Carefully:Congestive heart failure, myocardial ischemia, edema.
Pregnancy and lactation:Studies in humans were not conducted. In experiments on rats and rabbits, teratogenic action was not detected, but the presence of fetotoxic effect and delay in fetal growth were established. There is no information on the penetration of human milk. In experiments on rats, penetration of lactating rats into the milk was established. If it is necessary to treat rosiglitazone, it is necessary to stop breastfeeding.
Recommendations for FDA - Category C.
Dosing and Administration:The recommended initial dose is 4 mg per day.If necessary, according to the scheme of treatment, the dose can be increased to 8 mg per day.
The daily dose is taken in 1-2 divided doses, regardless of the meal.
Side effects:From the side metabolism: minor hypercholesterolemia, edema.
From the side hematopoiesis system: rarely - anemia.
From the side of cardio-vascular system: possible peripheral edema, heart failure (especially in older patients with long-term diabetes and receiving rosiglitazone in a dose of 8 mg per day); rarely congestive heart failure and pulmonary edema.
From the side digestive system: rarely - increased activity of hepatic enzymes (causality is not proven).
Interaction:Inductors CYP2C8 (rifampicin) accelerate the metabolism of rosiglitazone; It is possible to make changes in the scheme of hypoklikemic therapy (depending on the clinical response).
Inhibitors of CYP2C8 (gemfibrozil) slow down the metabolism of rosiglitazone. It may be necessary to reduce the dose of the drug with gemfibrozil, which is associated with the potential dose-dependence of side effects when combined with rosiglitazone.
Hypoglycemic drugs (especially those that promote the release of insulin) drugs (insulin, sulfonylureas) increase the risk of hypoglycemia. It may be necessary to reduce the dose of the concomitant.
Special instructions:The Cochrane systematic review of 18 studies involving 3888 patients suggests that treatment with rosiglitazone does not improve the patient's critical outcomes (mortality, complications of diabetes, side effects of therapy, quality of life, cost of treatment) and doubled the risk of edematous syndrome, cardiovascular complications and the frequency of bone fractures in women. The necessity of open publication of all the results of drug research at different stages is underlined.
With monotherapy rosiglitazone affects the control of glycemia; its effect is comparable with that of other hypoglycemic agents. Combination therapy has a significantly greater influence on the control of glycemia than prolonged therapy with a single hypoglycemic drug.
NB! Despite the well-known property of rosiglitazone to increase the content of total cholesterol, HDL cholesterol and LDL cholesterol,there is evidence of a sharp decrease in the concentration of HDL and apolipoprotein A-1 when the drug is used. The effect is reversible upon the cancellation of rosiglitazone. WHO recommends the determination of the content of HDL and triglycerides before the start of treatment and monitor their concentration in the future.