INSUFOR

 

TRADE NAME

Insufor

 

INTERNATIONAL NON-PROPRIETARY NAME

Metformin

 

CHEMICAL FORMULA

N,N-Dimethylimidodicarbonimidic diamide (as hydrochloride)

 

PHARMACEUTICAL FORM

Film coated tablets.

Description:

Insufor 500 mg: white colored, round, biconvex film coated tablets.

Insufor 850 mg: white colored, round, biconvex film coated tablets.

Insufor 1000 mg: white colored, oval, biconvex, both sides scored, film coated tablets.

 

COMPOSITION

Each film covered tablet contains

Active ingredient: metformin hydrochloride 500 mg, 850 mg or 1000 mg.

Excipients: povidone, pregelatinized starch, crospovidone, magnesium stearate.

The composition of film coating: Opadry II white 85F18422 (polyvinyl alcohol, titanium dioxide, macrogol, talc).

 

ATC CODE                             A10BA02

 

PHARMACOTHERAPEUTIC GROUP

Oral hypoglycemic drugs. Biguanides.

 

PHARMACOLOGICAL PROPERTIES

PHARMACODYNAMICS

Insufor is an oral hypoglycemic drug belonging to the biguanide group. The drug increases sensitivity of peripheral receptors to insulin, enhances muscle glucose uptake, suspends absorption of glucose and other carbohydrates from the gastrointestinal tract, inhibits gluconeogenesis in the liver, increases tissue sensitivity to insulin, suppresses insulin inactivation and decreases blood glucose level. Insufor cut down appetite, significantly reduces body weight in patients with diabetes mellitus, suffering from obesity, produces favourable effect on lipid metabolism (reduces total cholesterol, triglyceride and LDL levels), has antifibrinolytic properties, does not stimulate insulin secretion and does not demonstrate hypoglycemic action in healthy subjects.

PHARMACOKINETICS

Peak plasma concentration after oral administration is detected within 2.5 hours. The drug is absorbed well from the gastrointestinal tract; its bioavailability after oral administration of a 500-850 mg dose in healthy subjects is 50-60%. In case of parallel food intake metformin absorption decreases and slows down. Insufor is rapidly distributed in body tissues. The drug practically does not bind with plasma proteins. Its biotransformation is very insignificant; the drug is eliminated via kidneys. Insufor clearance in healthy subjects exceeds 400 ml/min., which confirms active tubular secretion. T_1/2 is 9-12 hours. In patients with renal insufficiency T_1/2 increases and metformin accumulation risk emerges.

 

therapeutic indicationS

- insulin-independent diabetes mellitus (type II), especially associated with obesity (in case of insufficient compensation of metabolism with diet and physical exercise);

- insulin-dependent diabetes mellitus (type I) in addition to insulin therapy (especially in case of marked obesity with secondary insulin resistance).

 

Dosage and administration

Tablets are administrated orally, in whole, during or immediately after meals, with sufficient amount of water.

Dosage regimen is established individually. Initial dose is 500 mg 2-3 times a day or 850 mg once a day. In 10-15 days the dose can be gradually increased depending on hypoglycemia level. Average maintaining dose of the drug is 1500-2000 mg/day, divided into 2-3 doses.

Maximum dose is 3000 mg/day. To decrease gastrointestinal side effects the daily dose should be divided into 2-3 doses.

 

CONTRAINDICATIONS

- individual intolerance (including history of hypersensitivity) of metformin;

- diabetes mellitus with predisposition to lactacidosis;

- diabetes mellitus with history of lactacidosis episodes;

- diabetic ketoacidosis;

- diabetic coma or precoma;

- serious hepatic function disorders (hepatitis, cirrhosis, steatosis);

- renal function disorders (creatinine level exceeding 12 mg% or 0.132 mmol/L in males and 0.123 mmol/L in females), acute diseases with risk of renal function disorder development;

- dehydration (due to diarrhea, vomiting);

- observance of hypocaloric diet (less than 1000 kcal/day);

- serious injuries and surgeries (when insulin therapy is indicated);

- serious respiratory diseases, fever, grave infectious diseases;

- grave cardiovascular diseases (heart failure decompensation, cardiogenic or toxic infectious shock, acute phase of myocardial infarction, peripheral arterial circulation disorder);

- gangrene;

- adrenal insufficiency;

- chronic alcoholism and acute alcohol intoxication;

- pregnancy and lactation.

 

SIDE EFFECTS

Gastrointestinal: anorexia (absence of appetite), nausea, vomiting, diarrhea, flatulence, abdominal pain (most often develop in the beginning of therapy and subside independently), metallic taste.

Metabolic: in exceptionally rare cases – lactic acidosis requiring drug withdrawal (weakness, somnolence, hypotension, reflectory bradyarrhythmia, respiratory disorders, abdominal pain, myalgia, hypothermia), hypoglycemia; B₁₂ vitamin deficiency (due to disturbance of B₁₂ vitamin and folic acid absorption).

Hematopoietic system: in individual cases of long-term administration – megaloblastic anemia.

Allergic reactions: skin rash, dermatitis.

 

SPECIAL INDICATIONS

Do not use in acute infections and exacerbation of chronic infectious inflammatory diseases, injuries, acute surgical diseases, in dehydration conditions.

Insufor should not be indicated together with the therapy with diuretics or other hypotensive drugs, administration of which can cause renal function disorder.

Dose titration in patients over 60 years of age must be performed under control of renal function status. Metformin should be indicated with caution to patients performing hard physical work (due to elevated risk of lactic acidosis development - lactacidosis).

During treatment renal (glomerular filtration) and hepatic function, as well as blood glucose level, must be controlled. Once a year vitamin B₁₂ level must be measured.

Metformin should not be indicated in case of plasma creatinine level exceeding 132 μmol/L in men and 123 μmol/L in women.

The patient must be warned about the need to visit a doctor in case of development of infectious diseases of the respiratory and urogenital systems, as well as in case of vomiting, abdominal pain, myalgias, general weakness (possible symptoms of lactacidois).

Do not use before or within 2 days after surgeries, as well as within 2 days before and after contrast-enhanced diagnostic tests (intravenous urography, angiography, etc.).

Adverse gastrointestinal effects can be alleviated with antacids, atropine derivatives or antispasmodic agents. In case of persistent dyspeptic events metformin should be withdrawn.

In case of transfer of the patient from the therapy with another drug (excluding chlorpropamide) to treatment with Insufor no interruption of therapy is needed. Still, in case of the transfer from chlorpropamide therapy a 2-week interval is needed due to the prolonged T_1/2 of the drug.

 

INFLUENCE ON ABILITY TO DRIVE AND OPERATE OTHER MECHANISMS

Insufor monotherapy does not influence on the ability to drive and operate mechanisms. Still, caution should be exercised in driving or performing works requiring increased attention, because concomitant administration of metformin with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide, etc.) increases risk of hypoglycemia development.

 

Pregnancy and lactation

Insufor is contraindicated in pregnancy. In case of planning or occurrence of pregnancy the drug must be withdrawn and insulin therapy initiated. Breastfeeding must be discontinued for the treatment period.

 

PEDIATRIC USE

Insufor can be administered in children since 10 years of age as monotherapy and in combination with insulin. Usual initial dose is 500 mg or 850 mg once daily during or immediately after meals. In 10-15 days the dose must be adjusted according to the results of blood glucose measurement. Maximum daily dose for children since 10 years of age is 2000 mg daily divided into 2-3 doses.

 

DRUG INTERACTIONS

Metformin action is potentiated by non-steroidal anti-inflammatory drugs, МАО inhibitors, oxytetracycline, ACE inhibitors, clofibrate derivatives, cyclophosphamide, and beta-adrenoblocking agents.

Concomitant administration of metformin with sulphonylurea derivatives, insulin, acarbose and salicylates may potentiate hypoglycemic action. The drug is compatible with sulphonylurea derivatives and insulin.

Nifedipine increases absorption, concentration and prolongs elimination of metformin.

Insufor effect is weakened by phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoine, nicotinic acid, calcium antagonists, and isoniazid.

In concomitant administration of metformin and danazol hypoglycemic effect may develop (such a combination is not recommended).

In concomitant administration of metformin and chlorpromazine keep in mind that the neuroleptic agent in high doses decreases insulin release and increases blood glucose level (which may require metformin dose adjustment under blood glucose control).

In case of parallel injections of beta-2-sympatomimetic drugs the hypoglycemic effect of metfomin may decrease (blood glucose level must be controlled and insulin should be prescribed, if needed).

In case of concomitant prescription glucocorticoids (for systemic and local administration) influence metformin effectiveness, decreasing glucose tolerance and increasing plasma glucose level, causing ketosis in some cases (if such a combination is needed, dose adjustment under blood glucose control is performed).

Metformin effect is weakened by thiazide and other diuretics. Furosemide increases maximum concentration of metformin by 22%. Insufor decreases maximum concentration and half-life period of furosemide by 31% and 42.3%, respectively. Parallel administration of loop diuretics and metformin may cause lactacidosis due to possible development of functional renal insufficiency.

Drugs secreted in renal tubules (amiloride, digoxin, morphine, procainamide, chinidin, chinin, ranitidine, triamterene and vancomycin) compete for tubular transport systems and in case of long-term therapy may increase metformin peak concentration by 60%.

Administration of iodine-containing radiopaque constant agents for radiological examination concomitantly with metformin may cause lactacidosis in the setting of functional renal failure.

Avoid ingestion of alcohol and ethanol-containing drugs concomitantly with metformin administration. Parallel administration of metformin with ethanol and ethanol-containing drugs increases the risk of lactacidosis development, especially while fasting or observing a low-calorie diet.

Care should be taken when combining the drug with indirect anticoagulants, as metformin weakens the effect of the latter.

Cimetidine inhibits metformin excretion, which increases the risk of lactacidosis development.

 

OVERDOSE

Symptoms: hypoglycemia and lactacidosis (lactic acidosis) may develop. Early signs of lactacidosis may include nausea, vomiting, diarrhea, fever, abdominal pain, muscular pain; then breathing acceleration, dizziness, consciousness impairment and coma may develop.

Treatment: immediate withdrawal of metformin, urgent hospitalization, blood lactate concentration determination; symptomatic therapy is performed, if necessary. Hemodialysis is the most important treatment method (it eliminates lactate from the body).

 

PACKAGING

Insufor 500 mg and 850 mg:

Film coated tablets. 15 tablets in a blister.

2, 4 or 6 blisters together with an enclosed leaflet in a carton box.

Insufor 1000 mg:

Film coated tablets. 10 tablets in a blister.

3, 6 or 9 blisters together with an enclosed leaflet in a carton box.

 

STORAGE CONDITIONS

Store at a temperature not exceeding 25°С.

Keep out of reach of children!

 

SHELF LIFE

3 years from the date of manufacture.

Do not apply after the expiry date.

 

SALES TERMS

Sold under prescription.

 

MANUFACTURER

The holder of trade mark and marketing authorization is

“INSUPHAR LABORATORIES İLAҪLARI LİMİTED ŞİRKETİ”, TURKEY.

 

Manufactured by

“İlko İlaç San. ve Tic. A.Ş.”, Konya ili, 3 Organize Sanayi Bölgesi Kuddusi Cad. 23 Sok. No:1 Selçuklu, Turkey.