Clinical and pharmacological group: & nbsp

Hypoglycemic synthetic and other agents

Included in the formulation
  • Diaglinide®
    pills inwards 
    AKRIKHIN HFK, JSC     Russia
  • Iglynide
    pills inwards 
  • Novonorm®
    pills inwards 
    Novo Nordisk A / S     Denmark
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    ONLS

    АТХ:

    A.10.B.X   Other hypoglycemic drugs

    A.10.B.X.02   Repaglinide

    Pharmacodynamics:

    Selective inhibition of ATP-dependent K+channels and the release of potassium ions from the cell with the resulting depolarization of the membrane, an increase in the intake of calcium ions, and stimulation of the exocytosis of insulin granules from the functioning β cells of the pancreatic islets.

    Pharmacokinetics:Suction fast and complete. F 56%. Time to reach a peak concentration of 1 h. Linkage to plasma proteins 98%. Completely metabolized as a result of oxidative biotransformation with subsequent conjugation with glucuronic acid. The main metabolites - oxidized dicarboxylic acid (M2), aromatic amine (M1) and acyl glucuronide (M7) - do not have a hypoglycemic effect. It was found that CYP3A4 is involved in the N-dealkylation of repaglinide to M2 and subsequent oxidation to M1. Half-life 1 hour. Elimination with feces (90%), with 60% of repaglinide removed in the form of M2, less than 2% in the form of the starting drug), kidney (8%). It is not removed during hemodialysis.
    Indications:Diabetes mellitus type 2 (with diet inefficiency, weight loss and exercise) in monotherapy or in combination with metformin or thiazolidinediones in cases where it is not possible to achieve satisfactory control of glycemia with monotherapy with repaglinide or metformin or thiazolidinediones.

    IV.E10-E14.E11   Non-insulin-dependent diabetes mellitus

    Contraindications:

    - Type 1 diabetes mellitus;

    - diabetic ketoacidosis; diabetic precoma and coma;

    - infectious diseases, large surgical interventions and other conditions requiring insulin therapy;

    severe liver dysfunction;

    - simultaneous administration of gemfibrozil;

    - Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

    - Pregnancy;

    - the period of breastfeeding;

    - age up to 18 years;

    - known hypersensitivity to repaglinide or to any of the components of the drug.

    Clinical studies in patients under the age of 18 years and older than 75 years were not conducted.
    Carefully:

    The need for more careful observation should be observed in violations of liver function of mild and moderate degree, febrile syndrome, chronic renal failure, alcoholism, general severe condition, malnutrition.

    Pregnancy and lactation:

    Contraindicated during pregnancy and breastfeeding.

    Recommendations FDA category C.

    Dosing and Administration:

    The initial dose is 0.5 mg / day, if the patient took another oral hypoglycemic drug - 1 mg. Correction of the dose is carried out once a week or once in 2 weeks (while focusing on the concentration of glucose in the blood as an indicator of response to therapy). The average daily dose is 4 mg 3 times / day; the maximum is 16 mg / day.

    Side effects:

    The most common side effect is hypoglycemia, the frequency of which depends, as with any kind of diabetes therapy, on individual factors such as eating habits, the dose of the drug, physical activity and stress.

    From the immune system: very rarely - generalized hypersensitivity reactions or immunological reactions such as vasculitis can be detected; unknown - hypersensitivity reactions, such as itching, rash, urticaria.

    From the side of metabolism: often - hypoglycemia; unknown - hypoglycemic coma, hypoglycemia with loss of consciousness. As with other hypoglycemic agents, hypoglycemia may develop with repaglinide.In most cases, these reactions are mild and can be eliminated by taking carbohydrates. In severe reactions, medical attention may be required, in particular, intravenous dextrose (glucose). The risk of developing hypoglycemia may increase with the interaction of repaglinide with other drugs.

    From the side of the organ of vision: very rarely - vision disorders. Changes in the concentration of glucose in the blood can lead to visual disturbances, especially at the initial stage of therapy with hypoglycemic drugs. However, usually these changes are transitory.

    From the cardiovascular system: rarely - cardiovascular diseases. The risk of cardiovascular disease is increased in type 2 diabetes mellitus. There was an increased risk of acute coronary syndrome in patients who received repaglinide, compared with patients receiving the sulfonylurea derivative, but not compared to patients receiving metformin or acarbose. However, the causal relationship is not established.

    From the digestive system: often - abdominal pain, diarrhea; very rarely - vomiting, constipation; unknown - nausea.

    From the liver and bile ducts: very rarely - violations of the liver function; in very rare cases, serious violations of liver function were reported (causal relationship with repaglinide was not established), increased activity of hepatic enzymes.
    Overdose:

    Symptoms: hypoglycemia.

    Treatment: Dextrose inside, intravenously.

    Interaction:β-Adrenoblockers - increased risk of developing severe hypoglycemic reactions, masking the symptoms of hypoglycemia.
    Means that cause hyperglycemia (thiazide diuretics, lithium preparations, slow calcium channel blockers, glucocorticoids, estrogens, oral contraceptives, isoniazid, a nicotinic acid, phenothiazines, phenytoin, sympathomimetics, thyroid hormones), inducers CYP3A4 (rifampicin, carbamazepine, an extract of grass perforated St. John's wort) - loss of control over glycemia.

    Chloramphenicol and drugs that bind to proteins in high degree: coumarin anticoagulants, NSAIDs, probenecid, MAO inhibitors, sulfonamides, inhibitors of CYP3A4 - aggravation of hypoglycemic effect of repaglinide.
    Special instructions:Prandial regulator of fast and short-acting glycemia.

    A systematic review of 15 studies involving 3781 participants, suggests the possibility of using meglitinides (including repaglinide) as a comparable hypoglycemic activity of metformin alternative (especially in the development of intolerance to metformin or with contraindications to his reception). There is no evidence of the effect of meglitinides on important long-term outcomes (eg, mortality). The experience of studying side effects arising from the use of meglitinides is still limited.

    It is comparable in effectiveness to glibenclamide and is more effective than glipizide. Predominantly, the intestinal route of excretion of the drug allows it to be administered to patients with impaired renal function. When combined with metformin, potentiation of hypoglycemic action is noted.

    Regular monitoring of blood glucose (fasting) and glycosylated hemoglobin (HbA1C) is necessary.

    The use of rosiglitazone, pioglitazone and repaglinide in combination with metformin or a sulfonylurea derivative is a stand-by method for treating some subtypes of diabetes mellitus of young,which proceeds according to the type of adult diabetes, and requires special control.

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