Gliben-M

Each 500/2.5-mg and 500/5-mg film-coated tablet contains 500 mg Metformin (Gliben-M) HCl equivalent to Metformin (Gliben-M) 390 mg, and Glibenclamide (Gliben-M) 2.5 mg and 5 mg, respectively.

This anti-diabetic medication is a combination of 2 drugs (glyburide and Metformin (Gliben-M)). It is used along with a diet and exercise program to control high blood sugar in patients with type 2 diabetes (non-insulin-dependent diabetes).Glyburide is a sulfonylurea and works by stimulating the release of your body’s natural insulin and by decreasing the amount of sugar that your liver makes. Metformin (Gliben-M) is a biguanide and works by decreasing the amount of sugar that your liver makes and that your stomach/intestines absorb.

General: As for all hypoglycemic agents, the dosage should be adapted according to the individual metabolic response (glycemia, HbA1c).

Initiation of Treatment: Treatment should be initiated with a dose of the combination product equivalent to previous individual doses of Metformin (Gliben-M) and Glibenclamide (Gliben-M); the dose being gradually increased depending on results on glycemic parameters.

Dosage Regimen: The dosage regimen depends on the individual posology: Once a Day: Morning at breakfast, 1 tab/day.

Twice a Day: Morning and evening, 2 or 4 tab/day.

Three Times a Day: Morning, noon and evening, for a dosage of 3, 5 or 6 tab/day (500 mg/2.5 mg film-coated tablets) or 3 tab/day (500 mg/5 mg film-coated tablets).

Dose Titration: The dosage should be adjusted every 2 weeks or longer, by increments of 1 tab, depending on glycemia results. A gradual increase in the dosage may aid gastrointestinal tolerance and prevent the onset of hypoglycemia.

Maximum Daily Recommended Dose: 500/2.5-mg film-coated tablets: 6 tab; 500/5-mg film-coated tablets: 3 tab. In exceptional cases, an increase up to 4 tab may be recommended.

Combination with Insulin Therapy: No clinical data are available on the concomitant use of Gliben-M with insulin therapy.

Elderly: The dosage of Metformin (Gliben-M)/Glibenclamide (Gliben-M) should be adjusted depending on renal function parameters [start with 1 tab of Metformin (Gliben-M) 500 mg/Glibenclamide (Gliben-M) 2.5 mg; regular checks on the renal function are necessary ].

Administration: The tablets should be taken with meals. The dosage regimen should be adjusted according to the individual eating habits. However, any intake must be followed by a meal with a sufficiently high carbohydrate content to prevent the onset of hypoglycemic episodes.

Hypersensitivity to Metformin (Gliben-M) HCl, Glibenclamide (Gliben-M), or other sulfonylureas and sulfonamides, or to any of the excipients of Gliben-M.

Type 1 diabetes (insulin-dependent diabetes), ketoacidosis, diabetic pre-coma. Renal failure or renal dysfunction (CrCl <60 mL/min). Acute conditions with the potential to alter renal function eg, dehydration, severe infection, shock or intravascular administration of iodinated contrast materials. Acute or chronic disease which may cause tissue hypoxia eg, cardiac or respiratory failure, recent myocardial infarction, shock. Hepatic insufficiency, acute alcohol intoxication, alcoholism; porphyria; and concurrent miconazole treatment.

Use in lactation: Metformin (Gliben-M) is excreted in the milk of lactating rats. In humans, in the absence of data concerning passage of Metformin (Gliben-M) and Glibenclamide (Gliben-M) into the breast milk, and in view of the risk of neonatal hypoglycemia, Gliben-M is contraindicated while breastfeeding.

You may be more likely to have hyperglycemia (high blood sugar) if you are taking Metformin (Gliben-M) with other drugs that raise blood sugar. Drugs that can raise blood sugar include:

isoniazid;

diuretics (water pills);

steroids (prednisone and others);

phenothiazines (Compazine and others);

thyroid medicine (Synthroid and others);

birth control pills and other hormones;

seizure medicines (Dilantin and others); and

diet pills, or medicines to treat asthma, colds or allergies.

You may be more likely to have hypoglycemia (low blood sugar) if you are taking Metformin (Gliben-M) with other drugs that lower blood sugar. Drugs that can lower blood sugar include:

some nonsteroidal anti-inflammatory drugs (NSAIDs);

aspirin or other salicylates (including Pepto-Bismol);

sulfa drugs (Bactrim and others);

a monoamine oxidase inhibitor (MAOI);

beta-blockers (Tenormin and others); or

probenecid (Benemid).

Some medications may interact with Metformin (Gliben-M). Tell your doctor if you are using any of the following drugs:

furosemide (Lasix);

nifedipine (Adalat, Procardia);

cimetidine (Tagamet) or ranitidine (Zantac);

amiloride (Midamor) or triamterene (Dyrenium);

digoxin (Lanoxin);

morphine (MS Contin, Kadian, Oramorph);

procainamide (Procan, Pronestyl, Procanbid);

quinidine (Cardioquin, Quinidex, Quinaglute);

trimethoprim (Proloprim, Primsol, Bactrim, Cotrim, Septra); or

vancomycin (Vancocin, Lyphocin).

This list is not complete and there may be other drugs that can interact with Metformin (Gliben-M). Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugsprescribed by other doctors. Do not start using a new medication without telling your doctor.

The following undesirable effects may occur under treatment with Metformin (Gliben-M)/Glibenclamide (Gliben-M). Frequencies are defined as follows: Very common (>1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Investigations: Uncommon: Average to moderate elevations in serum urea and creatinine concentrations. Very Rare: Hyponatremia.

Blood and Lymphatic System Disorders: These are reversible upon treatment discontinuation. Rare: Leukopenia, thrombocytopenia. Very Rare: Agranulocytosis, hemolytic anemia, bone marrow aplasia and pancytopenia.

Nervous System Disorders: Common: Taste disturbance.

Eye Disorders: Transient visual disturbances may occur at the start of treatment due to a decrease in glycemia levels.

Gastrointestinal Disorders: Very Common: Gastrointestinal disorders eg, nausea, vomiting, diarrhea, abdominal pain and loss of appetite.

These undesirable effects occur more frequently during treatment initiation and resolve spontaneously in most cases. To help prevent them, it is recommended that Metformin (Gliben-M)/Glibenclamide (Gliben-M) be taken in 2 or 3 doses taken evenly over the day. Increasing the dose slowly may also improve gastrointestinal tolerability.

Skin and Subcutaneous Tissue Disorders: Rare: Skin reactions eg pruritus, urticaria, maculopapular rash. Very Rare: Cutaneous or visceral allergic angiitis, erythema multiforme, exfoliative dermatitis, photosensitization, urticaria evolving to shock.

A cross reactivity to sulfonamide(s) and their derivatives may occur.

Metabolism and Nutrition Disorders: Hypoglycemia. Uncommon: Crises of hepatic porphyria and porphyria cutanea. Very Rare: Lactic acidosis. Decrease in vitamin B₁₂ absorption with a decrease in serum levels during long-term use of Metformin (Gliben-M). Consideration of such aetiology is recommended if a patient presents with megaloblastic anemia.

Disulfiram-like reaction with alcohol intake.

Hepatobiliary Disorders: Very Rare: Liver function test abnormalities or hepatitis requiring treatment discontinuation.