Starlix (Starlix)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceNateglinideNateglinide
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  • Starlix
    pills inwards 
    Novartis Pharma AG     Switzerland
    • Dosage form: & nbspcoated tablets
    Composition:

    1 tablet contains:

    active substance: nateglinide 60, 120 or 180 mg;

    auxiliary substances: lactose monohydrate, microcrystalline cellulose, povidone, crosscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide (E171), talc, macrogol 4000, silicon dioxide colloidal anhydrous, iron oxide red (E172) (only in tablets 60 mg and 180 mg), iron oxide yellow (only in the composition of tablets 120 mg).

    Description:

    Tablets of 60 mg: pink round with bevelled edges with an embossed inscription '' STARLIX ' on one side and the inscription "60" on the other side.

    Tablets 120 mg: yellow oval with an embossed inscription '' STARLIX ' on one side and the inscription "120" on the other side.

    180 mg tablets: red oval with inscription '' STARLIX ' on one side and the inscription "180" on the other side.

    Pharmacotherapeutic group:Hypoglycemic agent for oral administration.
    ATX: & nbsp

    A.10.B.X.03   Nateglinide

    Pharmacodynamics:

    Nateglinide is a derivative of the amino acid phenylalanine. The drug restores early secretion of insulin, which leads to a decrease in postprandial glucose concentration in the blood and glycosylated hemoglobin (HbA1c).

    Under the influence of nateglinide taken before meals, the early (or first) phase of insulin secretion is restored, which is disrupted (until complete absence) in patients with type 2 diabetes mellitus. Nateglinide interacts with K+atf-dependent channels of pancreatic β-cells. The selectivity of nateglinide in relation to K+ATP-dependent channels of β-cells of the pancreas are 300 times greater than those for these cardiac and vascular channels.

    Nateglinide, unlike other oral hypoglycemic agents, causes an increase in insulin secretion within the first 15 minutes after ingestion, thereby smoothing postprandial fluctuations ("peaks") of blood glucose concentration. In the next 3-4 hours the concentration of insulin returns to the initial values, thus avoiding the development of postprandial hyperinsulinemia, which can lead to delayed hypoglycemia.

    The secretion of insulin by β-cells of the pancreas caused by nateglinide depends on the concentration of glucose in the blood, and, as the glucose concentration decreases, the secretion of insulin decreases.Conversely, simultaneous intake of food or infusion of a dextrose solution leads to a marked increase in insulin secretion. The ability of Starlix at low blood glucose concentrations to negatively affect insulin secretion is an additional factor preventing the development of hypoglycemia, for example, in cases of skipping meals.

    Pharmacokinetics:

    When taking Starlix tablets before meals nateglinide quickly absorbed from the gastrointestinal tract (GIT). Time to reach the maximum concentration (Cmax) is less than 1 hour. Bioavailability of the drug is about 72%. For such indicators as the area under the curve "concentration-time" (AUC) and Cmax the pharmacokinetics of nateglinide in the dose range from 60 mg to 240 mg is linear in the appointment of type 2 diabetes mellitus type 3 3 times a day for one week. The time to reach the maximum concentration (Tmax) do not depend on the dose of the drug. When nateglinide is prescribed after a meal, a decrease in its absorption is noted -max, the value of C decreasesmax, while the completeness of absorption (magnitude AUC) Do not change, so it is recommended to use Starlix before meals.

    The association of nateglinide with serum proteins (predominantly with albumin and to a lesser extent - with acid α1-glycoprotein) is 97-99%. The degree of binding to proteins does not depend on the concentration of nateglinide in the plasma in the studied range - 0.1-10 μg / ml. The volume of distribution when the equilibrium state is reached is about 10 liters.

    Nateglinide is largely metabolized in the liver with the participation of microsomal isoenzymes of cytochrome P450 (70% isoenzyme CYP 2С9, by 30% - CYP ZA4). The three main metabolites of nateglinide, formed as a result of hydroxylation reactions, have a few times lower pharmacological activity than the starting substance.

    The drug is excreted from the body fairly quickly - during the first 6 hours after ingestion with urine, about 75% of the dose taken is excreted. Excretion is carried out mainly by the kidneys (approximately 83% of the dose), mainly in the form of metabolites; In an unchanged form, the kidneys produce about 6-16% of the dose. About 10% is excreted with calories. When used in doses up to 240 mg 3 times a day nateglinide Do not cumulate. Half-life is 1.5 hours.

    Indications:

    Diabetes mellitus type 2 - with ineffectiveness of diet and exercise.

    Contraindications:

    - Hypersensitivity to the active substance or any of the components of the drug

    - Type 1 diabetes mellitus

    - Diabetic ketoacidosis

    - Pregnancy, the period of breastfeeding

    - Age to 18 years (due to the lack of data from clinical studies for this age group of patients)

    - Expressed violations of the liver (in connection with the lack of data from clinical studies for this patient population)

    Carefully:

    The risk of developing hypoglycemia with Starlix, as well as other hypoglycemic drugs, is higher in elderly patients, undernourished, with adrenal or pituitary insufficiency, in patients with severe renal dysfunction.

    Pregnancy and lactation:

    Nateglenide did not have a teratogenic effect in experimental studies. The experience of using Starlix during pregnancy is currently absent, thus the safety of the drug for pregnant women has not been established. Do not use the drug during pregnancy.

    Nategelide is excreted in breast milk in rats.It is not known whether Starlix is ​​excreted in breast milk in women, so in connection with the potential risk of developing hypoglycemia in infants who are breastfeeding, Starlix should not be given to nursing mothers /

    Dosing and Administration:

    Starlix should be taken orally before meals. The interval between taking the drug and taking food should not exceed 30 minutes. As a rule, the drug is taken immediately before meals.

    When Starlix is ​​used as a monotherapy the recommended dose is 120 mg 3 times a day (before breakfast, lunch and dinner). If this dosage regimen fails to achieve the desired effect, the single dose can be increased to 180 mg. For patients with values HbA1c approaching the target, a single dose of Starlix at the beginning of treatment may be 60 mg. Correction of the dosing regimen is carried out on the basis of regularly determined indicators HbA1c .

    Combined therapy. Patients receiving monotherapy with Starlix and needy at accession of another hypoglycemic drug, may additionally be prescribed metformin. Conversely, patients already receiving metformin therapy may receive Starlix at a dose of 120 mg 3 times a day (before meals) as an additional remedy. If the background of metformin therapy is HbAic is approaching the desired (less than 7.5%), Starlix dose may be less - 60 mg 3 times a day.

    For elderly patients special correction of the dosing regimen is not required. For patients of advanced age there were no changes in the profile of efficacy and safety, as well as changes in pharmacokinetic characteristics.

    In patients with mild and moderate hepatic impairment correction of the dosing regimen is not required. There were no clinically significant differences in systemic bioavailability and T 1/2 nateglinide in patients with mild and moderate liver dysfunction, not suffering from diabetes, in comparison with healthy ones.

    In patients with impaired renal function of varying severity (including those on hemodialysis) correction of the dosing regimen is not required. There were no clinically significant differences in systemic bioavailability and T 1/2 in patients with moderate and severe (creatinine clearance 15-50 ml / min / 1.73 m2) impaired renal function and in patients on dialysis, compared with healthy ones.

    Side effects:

    As with other hypoglycemic drugs, hypoglycemia may develop with such manifestations as excessive sweating, tremor, dizziness, increased appetite, palpitation, nausea, weakness, malaise. These symptoms were mild and passed with the intake of carbohydrates if necessary. Values ​​of blood glucose concentrations of less than 3.3 mmol / l occur in 2.4% of patients who have had the above clinical signs.

    Rarely (> 0.01% to <0.1%): increased activity of liver enzymes in the blood; allergic reactions (rash, itching, urticaria).

    In the group of patients receiving Starlix and the group of patients receiving placebo, undesirable gastrointestinal effects (such as abdominal pain, dyspepsia, diarrhea), headache, and also undesirable phenomena associated with the characteristic for this group were noted with the same frequency patients with concomitant diseases, such as respiratory infections.

    Overdose:

    It was noted that Starlix was well tolerated when taking a dose of up to 720 mg per day for 7 days. Cases of overdose Starlix have not been described to date. Presumptive symptoms: severe hypoglycemia with clinical manifestations of varying severity. With the saved consciousness and the absence of neurological manifestations, a dextrose / sugar solution inside is indicated, as well as correction of the dose of the drug and / or meals. In severe hypoglycemia accompanied by coma, convulsions and other neurological manifestations, intravenous administration of a dextrose solution (glucose) is indicated. The use of hemodialysis for the removal of nateglinide from the bloodstream is inefficient due to its high binding to plasma proteins.

    Interaction:

    Nateglinide is largely metabolized by cytochrome P450 isoenzymes - CYP 2C9 (70%) and CYP FOR (30%) (data received in vitro and in vivo). According to the data received in vitro, nateglinide is a potential inhibitor CYP 2C9. No effect of nateglinide on isoenzyme activity CYP AP4 in vitro it was not found. Generally, nateglinide does not have any significant potential for clinically significant pharmacokinetic interactions.

    Nateglinide does not affect the pharmacokinetic properties of warfarin (a substrate for CYP FOR4 and CYP 2C9), diclofenac (substrate for CYP 2C9) and digoxin. Thus, with the simultaneous administration of Starlix and such drugs as warfarin, diclofenac and digoxin dosage adjustment is not required. Also it was not revealed clinically relevant pharmacokinetic interactions of Starlix with other oral hypoglycemic drugs, such as metformin and glibenclamide.

    In a study of the interaction of nateglinide with sulfinpyrazone, a strong and selective inhibitor CYP 2C9, there was a moderate increase AUC (28%) in healthy volunteers, with constant values ​​of Cmax and T1 / 2. Thus, with the co-administration of nateglinide with inhibitors CYP 2C9, the probability of prolongation of the effect and the potential risk of developing hypoglycemia can not be ruled out.

    Such highly protein-binding drugs as furosemide, propranolol, captopril, nicardipine, pravastatin, warfarin, phenytoin, acetylsalicylic acid, glibenclamide and metformin do not affect the binding of nateglinide to plasma proteins in vitro. The same way, nateglinide does not displace from the bond with the protein propranolol, glibenclamide, nicardipine, warfarin, phenytoin, tolbutamide and acetylsalicylic acid.

    It should be borne in mind that some drugs affect glucose metabolism, so when they are administered simultaneously with hypoglycemic drugs, including with Starlix, glucose concentration changes are possible and medical supervision is required. Hypoglycemic effects of Starlix can be enhanced by simultaneous administration with non-steroidal anti-inflammatory drugs, salicylates, monoamine oxidase (MAO) inhibitors, nonselective beta-blockers. On the contrary, the hypoglycemic effect of Starlix can be weakened with simultaneous administration of thiazide diuretics, glucocorticosteroids, sympathomimetics, thyroid hormone preparations. When prescribing these drugs concurrently with nateglinide or their withdrawal in the case of combination therapy, the glucose level in patients should be closely monitored.

    The simultaneous use of Starlix and another hypoglycemic drug can provoke a marked decrease in the concentration of glucose in the blood.

    Simultaneous reception of beta-blockers can mask manifestations of hypoglycemia.

    Special instructions:

    When Starlix is ​​used, precautions should be taken regarding the occurrence of hypoglycemia. Reducing the concentration of glucose in the blood can be triggered by alcohol intake and increased physical exertion.

    Given that the main therapeutic effect of Starlix is ​​to reduce the prandial concentration of glucose in the blood (this concentration determines the value of the indicator HbA1c , To assess the therapeutic effectiveness of the drug, you can also use the blood glucose concentration index after 1-2 hours after eating.

    Starlix can be used as a monotherapy or in combination with hypoglycemic drugs with a different mechanism of action, for example, metformin.

    Effect on the ability to drive transp. cf. and fur:Patients working with mechanisms and driving vehicles should take special precautions to prevent hypoglycemia.
    Form release / dosage:

    Tablets coated with 60 mg, 120 mg, 180 mg

    12 tablets in a blister pack. 1, 2, 5, 7, 10 or 30 blisters with instructions for use in a cardboard bundle.

    Storage conditions:

    At a temperature of no higher than 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N014606 / 01
    Date of registration:07.02.2012
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC
    Information update date: & nbsp07.02.2012
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