What is rosiglitazone?
Rosiglitazone is an antidiabetic agent from the group of insulin sensitizers for the treatment of diabetes mellitus type 2. The operating principle is to increase the sensitivity of the tissue to insulin. The body's insulin is consequently again effectively able to lower elevated blood sugar levels.
Since November 2010 rests on the orders of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany, the transport capacity for drugs containing rosiglitazone. Your risk-benefit ratio was classified as total unfavorable from the Committee for Human Medicinal Products (CHMP) at the European Medicines Agency (cardiovascular risks, frequent heart attacks). Recent studies show, however, that the initial concerns are unfounded possibly, according to a review of rosiglitazone increases (trade name Avandia) is not the risk of heart attack. The raw data were manipulated more or less consciously in the original study, which was also not blinded. However, the economic interest in the recent commercialization of the drug is currently low because the patent has already expired.
Rosiglitazone seems the conventional antidiabetic drugs at higher costs not to be superior.
Pharmacological information
Effects
The mechanism of action of the insulin sensitizers rosiglitazone activated according to oral intake in the nucleus the PPAR (peroxisome proliferator-activated receptors) of type γ. This receptor is involved in the regulation of various mechanisms in the carbohydrate and lipid metabolism. Activation increased the sensitivity of cells to the liver, muscle and fat insulin (reduction of insulin resistance). The effect of added insulin is enhanced. Fatty acids and glucose are thus increasingly taken into the cells and metabolised. In the liver also reduces the formation of glucose
Rosiglitazone addition to their effects in the metabolism additionally anti-inflammatory properties. It lowers the concentration of NF-KB (nuclear factor kappa B) and increasing the concentration of IkB (inhibitory kappa B) in inflammatory cells. Because animal studies a therapeutic effect in Alzheimer's disease and Alzheimer's disease was discussed.
Pharmacokinetics
The maximum levels in the blood is achieved because of the rapid absorption from the gut in about one hour. The bioavailability amounts to 99%. The plasma protein binding is almost 100%. The degradation occurs via the cytochrome P450 system of the liver, the metabolites are not more active. Their elimination is done to 70% through the kidneys (renal), 30% of bowel movements. The plasma half-life is three to four hours, in liver disease it can be extended. Dosage adjustment in renal impairment is not necessary.
Clinical Data
Areas of application
Rosiglitazone is indicated for the treatment of diabetes mellitus type 2. rosiglitazone is used either alone or in combination with other drugs.
Monotherapy
The monotherapy with rosiglitazone is indicated in adults whose blood sugar through diet and exercise is not sufficiently adjustable and is unsuitable for metformin.
Dual combination therapy
Co-administration with either metformin or a drug from the group of the sulfonylureas is displayed when a sole administration of these agents is insufficiently effective.
Triple-combination therapy
Co-administration with metformin and a sulfonylurea is indicated in adults whose blood sugar with a dual-combination therapy is poorly adjusted.
Side Effects
The most common adverse effects are edema, anemia (anemia), weight gain and increase in blood cholesterol levels (hypercholesterolemia). These occur in combination with insulin to significantly more frequently than with single medication with rosiglitazone. In combination with insulin or a sulfonylurea also very commonly dose-dependent hypoglycaemia (hypoglycemia) on. Next, there may be an increased appetite and body weight, constipation (constipation) and liver damage with elevation of transaminases, but only very rarely with overt liver inflammation (hepatitis) come. Rarely there is an inflammation of the pancreas (pancreatitis), anaphylactic reactions, angioedema to, urticaria, rash and itching of the skin or a macular of the eye. Especially in combination with insulin can cause a lack of oxygen to the heart muscle.
In an analysis of 42 studies, published in June 2007 in the New England Journal of Medicine, an increased heart attack risk by 43% was observed. The manufacturer of the drug and the European Medicines Agency questioned the validity of the meta-analysis. An independent control of the study data now confirms the doubt, but imagine rosiglitazone is no increased risk of heart attacks. The FDA has therefore already loosened the requirements for prescribing rosiglitazone.
Due to the alleged increased risk of cardiovascular disease in rosiglitazone-preparations, the European Medicines Agency (EMA) recommended eventually in September 2010 to delist in Europe. The German Federal Institute for Drugs and Medical Devices (BfArM) came to this recommendation, so that rosiglitazone since November 2010 are no longer available in Germany.
According to a former employee of the Food and Drug Administration (FDA) of Avandia maker GlaxoSmithKline PLC has retained data on the risk. An expert panel of the same authority has a majority expressed concerns about "Avandia", also a majority of the same but pronounced for keeping the drug under certain conditions on the market.
Interactions
Rosiglitazone is primarily metabolized by the cytochrome P450 isoenzymes CYP2C8 and CYP2C9. Therefore, there may be variations in systemic exposure with concomitant use of drugs with influence of CYP2C8 inducers such as rifampicin, trimethoprim and gemfibrozil. Interaction with phenytoin, carbamazepine, phenobarbital and St. John's wort can not be excluded. The pharmacokinetics of coumarin derivatives, warfarin and Acenocoumarol that are also metabolized by CYP2C9, however, is unaffected. Next an increase in the activity of methotrexate is possible. Moderate alcohol consumption while taking has no influence on the effect.
Contraindications
Rosiglitazone is contraindicated in case of hypersensitivity to rosiglitazone, in heart failure and liver dysfunction. The combination with insulin has not been displayed due to the greatly increased rates of side effects.
For the application under the age of ten years are no data. An application is not recommended. Rosiglitazone crosses the placenta during pregnancy and lactation, the application should therefore not be made if no data on toxicity in humans also exist.
Chemical and pharmaceutical information
Rosiglitazone is chiral. The commercial preparations containing the drug as a racemate (1: 1 mixture of enantiomers).
Rosiglitazone is formulated orally applicable and as film-coated tablet. The tablets contain the drug as the salt of maleic acid (rosiglitazone maleate). Rosiglitazone is available on prescription.