Alogliptin (Alogliptin)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Hypoglycemic synthetic and other agents

Included in the formulation
  • Vipidia
    pills inwards 
    Takeda Pharmaceuticals USA, Inc.     USA
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    A.10.B.X   Other hypoglycemic drugs

    A.10.B.H.04   Alogliptin

    Pharmacodynamics:

    Hypoglycemic agent. Alogliptin - Selective inhibitor of dipeptidyl peptidase-4, which inactivates incretin hormones (glucose-dependent insulinotropic peptide, glucagon-like peptide-1). Suppression of dipeptidyl peptidase-4 increases the level of active incretins in blood plasma, which improves glycemic control. Glucose-dependent insulinotropic peptide and glucagon-like peptide-1 simulate glucose-dependent insulin secretion by beta cells of the pancreas. Glucagon-like peptide-1 has an additional effect of suppressing the glucose-dependent secretion of glucagon, which contributes to a sense of satiety, a reduction in food intake and a slowdown in the devastation of the stomach.

    Pharmacokinetics:

    The pharmacokinetics of alogliptin is similar in people with healthy and diabetic patients of type 2. With oral administration of a single dose of 800 mg in both healthy and diabetic patients, the peak concentration of alogliptin in plasma (mean Tmax) is observed after 1-2 hours.Accumulation of the substance in the body is minimal. Absolute bioavailability of about 100%, food does not affect suction. 20% of the substance binds to plasma proteins. The half-life is 21 hours, the kidney clearance is 9.6 l / h, the total clearance is 14 l / h. 76% of the substance is excreted in the urine, 13% - with feces.

    After a single intravenous injection of 12.5 mg of alogliptin to healthy people, the volume of distribution in the final phase was 417 liters, indicating a good distribution of the substance in the tissues.

    Alogliptin is not subjected to intensive metabolism, 60-71% of the substance is excreted unchanged in urine. Two secondary metabolites of the substance are N-demethylated (less than 1% of the starting compound) and N-acetylated alogliptin (less than 6% of the starting compound). N-demethylated metabolite is active, is an inhibitor of dipeptidyl peptidase-4. The N-acetylated metabolite is not active. The cytochromes CYP3A4 and CYP2D6 are involved in the metabolism of alogliptin, but their role is not great. About 10-20% of the dose of the drug undergoes transformation in the liver under the influence of cytochromes.

    Indications:

    It is prescribed for type 2 diabetes in addition to diet and exercise to improve blood glucose control.

    ICD-10

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

    Contraindications:Hypersensitivity to alogliptin, including anaphylaxis, Quincke's edema or severe skin reactions, including Stevens-Johnson syndrome.

    Pregnancy. Lactation.

    Age to 18 years.

    Severe hepatic insufficiency.

    Carefully:Acute pancreatitis in the anamnesis.

    Renal failure is of moderate severity.

    At pathological parameters of hepatic tests.

    In combination with preparations of sulfonylureas and insulin.

    Pregnancy and lactation:

    Do not administer during pregnancy and lactation.

    Pregnancy. Category B by classification FDA, Studies in animals showed no danger to the fetus, human studies have not been conducted.

    Lactation. It is not known whether alogliptin in the milk.

    Dosing and Administration:

    Assigned to 25 mg orally every day.

    Dosage for impaired renal function:

    • weakly expressed (creatinine clearance ≥ 60 l / min) - dose adjustment is not required.
    • moderatecreatinine clearance ≥ 30 to <60 ml / min) - the dose is reduced to 12.5 mg orally every day.
    • heavy (creatinine clearance ≥ 15 to <30 mL / min) or in the terminal stage of renal failure (creatinine clearance less than 15 l / min) or, if necessary, hemodialysis - the dose is 6.25 mg orally every day.

    Can be administered regardless of the dialysis schedule. Not studied in peritoneal dialysis. Before the appointment and periodically during the treatment should be checked the function of the kidneys

    Dosing in case of liver damage:

    • mild and moderate (A and B on the Child-Pugh scale) - dose adjustment is not required.
    • heavy (C on the Child-Pugh scale) - not studied.

    Alogliptin can be taken with or without food.

    Geriatric patients do not require dose adjustment.

    Side effects:

    From the gastrointestinal tract

    Frequent (1% -10%): abdominal pain, gastroesophageal reflux disease.

    Rare (0.1% -1%): pancreatitis.

    According to clinical studies, pancreatitis was observed in 11 of 5902 (0.2%) patients who received 25 mg of alogliptin daily. This compares with an indicator of less than 0.1% (5/5183) of patients in the control group. In a combined analysis of 13 studies involving patients who received 25 mg or 12.5 mg of the drug, active control and placebo control, the event rate was 2, 2, 1, 0 per 1000 patient-years, respectively.

    From the side of the musculoskeletal system

    Arthralgia (no information on the frequency is given).

    From October 2006 to December 2013, the FDA Reporting System received 33 reports of severe arthralgia. In each case, patients took 1 or more inhibitors of dipeptidyl peptidase-4. 10 patients were hospitalized due to disability. In 22 cases, symptoms appeared within the first month after the initiation of therapy, in 23 cases the symptoms went away more quickly than a month after withdrawal.

    From the side of the liver

    Post-marketing reports on elevation of hepatic enzyme levels, fulminant hepatic insufficiency.

    Hypersensitivity

    It is rare (0.6%). According to post-marketing reports, manifested in the form of anaphylaxis, urticaria, Quincke edema, severe skin reactions (Stevens-Johnson syndrome).

    From the nervous system

    Headaches (1% -10%).

    From the respiratory system

    Often (1% -10%): nasopharyngitis, respiratory infections.

    From the skin side

    Often (1% -10%): skin itching.

    According to post-marketing reports, there are exfoliative skin lesions, including Stevens-Johnson syndrome, erythema polymorph, Quincke's edema, urticaria.

    Metabolic disorders

    Frequent (1% -10%): hypoglycemia.

    According to the results of the cumulative analysis, the hypoglycemic risk of the medication was found to be neutral.

    Overdose:

    According to the manufacturer's instructions, the largest single dose given to healthy people was 800 mg, patients with type 2 diabetes were prescribed 400 mg daily for two weeks. This is equivalent to exceeding the recommended clinical dose by 32 and 16 times, respectively. Serious side effects with the use of such doses were not revealed.

    In case of an overdose, the treatment is symptomatic in accordance with the clinical status of the patients. Hemodialysis is not an effective remedy for an overdose of alogliptin.

    Interaction:

    Alogliptin is not subjected to intensive metabolism, the metabolism associated with cytochrome P450 is negligible. Alogliptin showed no significant effect on other drugs metabolized by cytochrome isoenzymes (warfarin, caffeine, pioglitazone, glyburide, tolbutamide, dextromethorphan, atorvastatin, ethinyl estradiol, norethindrone, midazolam) or substrates PGP (digoxin, fexofenadine).

    In the same way,in the pharmacokinetics of alogliptin, there is no change in co-administration with gemfibrozil, pioglitazone, fluconazole, ketoconazole, atorvastatin, cyclosporine and digoxin.

    Alogliptin is excreted mainly by the kidneys. Significant interactions with the studied drugs, excreted by the kidneys (metformin, cimetidine), was not found.

    Special instructions:

    Pancreatitis. Post-marketing reports refer to cases of acute pancreatitis in patients taking alogliptin. Patients should be examined for signs and symptoms pancreatitis. In case of suspicion of this disease, alogliptin must be immediately canceled, appropriate measures should be taken. Whether patients with pancreatitis in history are at risk for developing acute pancreatitis while taking alogliptin, it is not known.

    Hypersensitivity. In the case of manifestations of hypersensitivity reactions, alogliptin should be canceled. It is necessary to clarify whether there are other reasons for such reactions, and to choose another antidiabetic therapy. It should be used with caution in patients with Quinck's edema after the application of otherinhibitors dipeptidyl peptidase-4 in the anamnesis.

    Use with drugs that can cause hypoglycemia. When used with insulin or stimulants, insulin secretion (sulfonylureas) may require a reduction in the dose of insulin or a stimulant of secretion to reduce the risk of hypoglycemia.

    Hepatotoxicity. Post-marketing reports refer to fatal and non-fatal cases of liver failure (some reports did not contain enough information to determine the cause of the problem). Prior to the appointment of alogliptin, it is recommended that liver samples be taken and patients examined. Start therapy in patients with abnormal liver tests with caution.

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