INSTRUCTION
for medical use of the preparation

 Maglifort 500

  Maglifort 850

   Maglifort 1000

 

Composition:

Active substance: metformin hydrochloride;

1 tablet, film-coated, contains metformin hydrochloride 500 mg, 850 mg, 1000 mg;

Excipients tablets of 500 mg or 850 mg: sodium starch glycolate (type A), povidone, corn starch, magnesium stearate, colloidal silicon dioxide anhydrous,

Film coat: hypromellose, polyethylene glycol 6000, talc, titanium dioxide (E 171), propylene glycol;

Excipients tablets of 1000 mg, povidone, magnesium stearate,

Film coat: hypromellose, polyethylene glycol 6000, polyethylene glycol 400.

Pharmaceutical form.

Film-coated tablets.

Pharmaceutical group.

Antidiabetic preparations. Oral hypoglycemic agents, excluding insulin. Metformin. ATC code A10V A02.

Clinical particulars.

Therapeutic indications.

Type 2 diabetes mellitus (insulin-dependent) after ineffective diet therapy, especially in patients who suffer from obesity:

- As monotherapy or combination therapy in combination with other oral hypoglycemic agents or with insulin to treat adults;

- As monotherapy or combination therapy with insulin for the treatment of children over 10 years-old.

Reducing the complications of diabetes in adults with type 2 diabetes and overweight who used metformin as first-line drug after an ineffective diet.

Contraindications. 

- Hypersensitivity to metformin hydrochloride or to any of the excipients;

- Diabetic ketoacidosis, diabetic pre-coma, coma;

- Renal dysfunction (creatinine clearance < 60 ml/min).;

- Acute conditions with the potential to alter renal function such as: Dehydration, severe infection, shock;

- Acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure,, recent myocardial infarction, shock;

- Hepatic insufficiency, acute alcohol intoxication, alcoholism.

Method of administration.

Monotherapy and combination with other oral antidiabetic agents:

Adults. The usual starting dose is one tablet of 500 mg or 850 mg (Maglifort 500 or Maglifort 850) 2-3 times a day during or after a meal.

After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. 

A slow increase of dose may improve gastro-intestinal tolerability.

The maximum recommended dose is 3000 mg daily, divided into 3 doses.

In the treatment with high doses Maglifort 1000 is used.

In the case of tranfer to treatment with Mehlifort, you should stop taking other antidiabetic agent.

Combination with insulin:.

Metformin and insulin may be used in combination therapy to achieve better blood glucose control.The usual starting dose of Maglifort is one tablet of 500 mg or 850 mg 2-3 times a day, while insulin dosage is adjusted on the basis of blood glucose measurements.

Monotherapy or combination therapy in combination with.

Children. Maglifort is used for children over 10 years-old. The usual starting dose is one tablet of 500 mg or 850 mg (Maglifort 500 or Maglifort 850) once daily during or after a meal. After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements.

A slow increase of dose may improve gastro-intestinal tolerability.

The maximum recommended dose is 2000 mg daily, divided into 2-3 intakes.

Elderly. Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary (see. section «Precautions for use»).

Undesirable effects.

The following undesirable effects may occur with metformin.

Frequencies are defined as follows: very common: ≥1/10; common ≥1/100, <1/10; uncommon ≥1/1,000, <1/100; rare ≥1/10,000, <1/1,000; very rare <1/10,000

Nervous system disorders

Common: Taste disturbance.

Gastrointestinal disorders.

Very common: nausea, vomiting, diarrhoea, abdominal pain and loss of appetite, metallic taste in the mouth and meteorism. These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent the undesirable effects from the digestive tract, a slow increase of the dosage and the use of preparation 2-3 times a day during or after a meal are recommended.

Blood system.

Isolated reports: megaloblastic anemia.

Skin and subcutaneous tissue disorders.

Very rare: Skin reactions such as erythema, pruritus, urticaria

Metabolism and nutrition disorders.

Very rare: Lactic acidosis.

Decrease of vitamin B12 absorption with decrease of serum levels during long-term use of metformin. Consideration of such an aetiology is recommended if a patient presents with megaloblastic anaemia.

Hepatobiliary disorders

Isolated reports of liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.

Overdose.

Hypoglycaemia has not been seen with Maglifort doses of up to 85 g, although lactic acidosis has occurred in such circumstances. The most effective method to remove lactate and Maglifort is haemodialysis. In the case of lactic acidosis Maglifort treatment should be discontinued immediately. The patient must be hospitalized and the concentration of lactate should be retermined to clarify the diagnosis. Also the symptomatic treatment is carried out.

Pregnancy and lactation.

When the patient plans to become pregnant and during pregnancy the Maglifort treatment should be discontinued. Tell your doctor and insulin must be prescribed.

Data on permeation of metformin into breast milk is not available; the preparation is contraindicated for use during breastfeeding. If it is necessary to conduct the treatment with Maglifort during lactation, breast-feeding should be discontinued.

Children.

Maglifort is used for the treatment of children at the age of 10 and more.

Precautions for use.

Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin accumulation. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure. Risk factors of lactic acidosis: poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency or any condition associated with hypoxia.

 Lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma.If metabolic acidosis is suspected, metformin should be discontinued and the patient should be hospitalised immediately.

Renal failure. As metformin is excreted by the kidney, creatinine clearance and/or serum creatinine levels should be determined before initiating treatment and regularly thereafter, especially in patients with renal dysfunction and in elderly patients. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with an NSAID.

Administration of iodinated contrast agent. As the intravascular administration of iodinated contrast materials in radiologic studies can lead to renal failure, metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.

Surgery. Maglifort should be discontinued 48 hours before elective surgery under general, spinal or peridural anaesthesia. Therapy should be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and only if renal function has been established.

Children. The results of clinical studies have not revealed the action of metformin on growth and puberty in children. However, there are no data on the metformin’s action on growth and puberty during prolonged use of Maglifort, so special caution should be exercised in situation, when the preparation is used for children in puberty, especially aged 10 to 12 years.

All patients should continue their diets and monitor the laboratory indications. Hypoglycemic action may be increased in combined treatment of Maglifort and insulin or sulfonylureas.

Effects on ability to drive and use machines

Maglifort monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.

However, patients should be alerted to the risk of hypoglycaemia when metformin is used in combination with other antidiabetic agents (sulphonylureas, insulin, repaglinide).

Interaction with other medicinal products and other forms of interaction

Concomitant use not recommended

Increased risk of lactic acidosis in acute alcohol intoxication, particularly in case of fasting or malnutrition, as well as hepatic insufficiency. Avoid consumption of alcohol and alcohol-containing medications during the Maglifort treatment.

Iodinated contrast agents can cause the development of lactic acidosis in patients with diabetes on the background of functional renal failure. Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards.

To avoid hyperglycemic action the concomitant intake of danazol is not recommended. If necessary Danazol treatment and after its discontinuation the Maglifort dose adjustment is required under the control of glucose level.

Associations requiring precautions for use

Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.

In concomitant use of ACE-inhibitors, the hypoglycemic action may be increased.

In high doses (100 mg daily) Chlorpromazine increases glycemia by reducing insulin release. In the treatment with neuroleptic and after its discontinuation the Maglifort dose adjustment is required under the control of glucose level..

Pharmacological properties.

Pharmacodynamic properties. Metformin decreases hyperglycemia and does not cause hypoglycemia.Unlike sulfonylureas It does not stimulate insulin secretion and therefore does not produce hypoglycaemia. In blood plasma It decreasesbothbasalandPostprandialplasmaglucoseafter take a meal.

Metformin may act via 3 mechanisms:

- reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis;

- reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis;

- delay of intestinal glucose absorption.

Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.

Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).

Independently of its action on glycaemia, immediate-release metformin has favourable effects on lipid metabolism: reduces the content of total cholesterol, low density lipoproteins and triglycerides.

Increases the glucose utilization by cells and the sensitivity of peripheral receptors for insulin. Inhibits gluconeogenesis in the liver. Delays absorption of carbohydrates in the intestines.

Pharmacokinetic properties.

Absorption. After an oral intake, metformin is almost completely absorbed from the digestive tract, 20-30% excreted in feces. Time to reach maximum concentration (T_max) makes 2,5 hours. The absolute bioavailability is about 50-60%.

The absorption of metformin is reduced and it slows down in concomitant food intake.

Distribution. Plasma protein binding is negligible. Metformin partitions into erythrocytes.. The blood peak is lower than the plasma peak and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean Vd ranged between 63-276 l.

Metabolism. Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.

Elimination. Renal clearance of metformin is> 400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 hours. When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.

Pharmaceutical particulars.

Basic physical and chemical properties::

Maglifort 500 or Maglifort 850: tablets of a round form with a biconvex surface, film-coated, white to nearly white;

Maglifort 1000: capsule-shaped tablets with a biconvex surface, with a mark on both sides, film-coated, white to nearly white;.

Shelf life.

3 years.

Special precautions for storage.

Store in the original package at temperature not exceeding 25 ^ºС.

Keep out of the reach of children.

Packaging.

10 tablets in a strip.

1 or 3 strips in a carton box.

Terms of dispensing. On prescription.

Manufacturer.

Indoco remedies ltd.

Site.

L-14, Verna Industrial Area, Verna, Salcete, Goa - 403 722, India.

 

Applicant.

1. M. Biotech ltd.

 

Site.

Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom.