Formina Pliva - instructions for use, dose, side effects, contraindications

Composition:1 tablet, film-coated, contains: active substance metformin hydrochloride 850.0 mg; auxiliary substances: sodium carboxymethyl starch 34.0 mg, corn starch 17.0 mg, povidone 68.0 mg, silicon colloidal dioxide 11.9 mg, magnesium stearate 5.1 mg; shell: hypromellose 8.0 mg, titanium dioxide (E171) 3.2 mg, propylene glycol 0.616 mg, macrogol-6000 0.616 mg, talc 5.1 mg.

Description:Round, biconvex tablets, covered with a film coat, white.

Pharmacotherapeutic group:Hypoglycemic agent for oral administration of the biguanide group.

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:Metformin - oral hypoglycemic agent from the biguanide group. In patients with diabetes mellitus, it reduces the concentration of glucose in the blood by suppressing gluconeogenesis in the liver, reducing the absorption of glucose from the gastrointestinal tract (GIT) and increasing its utilization in tissues by increasing their sensitivity to insulin (predominantly striated muscle, to a lesser extent - adipose tissue). Stimulates intracellular glycogenesis, activating glycogen synthase. Does not stimulate the secretion of insulin, hypoglycemic reactions do not cause. Has an effect on lipid metabolism - reduces the concentration in the blood serum of triglycerides, cholesterol and low density lipoproteins. Stabilizes or reduces body weight. Has a fibrinolytic effect due to inhibition of the inhibitor of tissue-type plasminogen activator.

Pharmacokinetics:Suction. After taking the drug inside metformin sufficiently absorbed from the digestive tract. Absolute bioavailability is 50-60%. The maximum plasma concentration (Cmax) is approximately 2 μg / ml or 15 μmol and is achieved after 2.5 hours.After 7 hours, the absorption from the gastrointestinal tract ends, and the concentration of metformin in the plasma gradually decreases. With simultaneous intake of food, absorption of metformin decreases and slows down.
Distribution. Metformin practically does not bind to plasma proteins and is quickly distributed into body tissues. Partly associated with erythrocytes. It accumulates in the salivary glands, liver and kidneys. The apparent volume of distribution is 63-276 liters.
Metabolism and excretion. It is excreted by the kidneys unchanged. The clearance of metformin in healthy individuals is 400 ml / min, which indicates active glomerular filtration and tubular secretion. The half-life (T1 / 2) is approximately 6.5 hours.
Pharmacokinetics in special clinical cases. In patients with renal insufficiency, renal clearance of the drug decreases in proportion to a decrease in creatinine clearance, T1 / 2 increases, which leads to an increase in the concentration of metformin in the blood. Cumulation is possible.

Indications:Diabetes mellitus type 2 in adults (especially in obese patients) with ineffectiveness of diet and exercise, as a monotherapy or in combination with other oral hypoglycemic agents or insulin.

Contraindications:- Hypersensitivity to metformin or to any auxiliary substance.
- Diabetic ketoacidosis, diabetic precoma, coma.
- Renal failure or renal dysfunction (creatinine clearance (CC) less than 60 ml / min).
- Acute conditions that occur with a risk of developing renal dysfunction:
-dehydration (with diarrhea, vomiting), fever, severe infectious diseases;
- states of hypoxia (shock, sepsis, kidney infections, bronchopulmonary diseases).
- Clinically expressed manifestations of acute and chronic diseases, which can lead to the development of tissue hypoxia (including cardiac or respiratory failure, acute myocardial infarction).
- Extensive surgery and trauma, when insulin therapy is indicated (see section "Special instructions").
- Hepatic failure, a violation of the liver.
- Chronic alcoholism, acute alcohol poisoning.
- Lactic acidosis (including in the anamnesis).
- Use for at least 48 hours before and within 48 hours after carrying out radioisotope or X-ray studies with the introduction of an iodine-containing contrast medium (seesection "Interaction with other drugs").
- Period not less than 48 hours before and within 48 hours after surgical interventions under general anesthesia, spinal or epidural anesthesia.
- Compliance with a hypocaloric diet (less than 1000 kcal / day).
- Children under 18 years.

Carefully:In patients over 60 years of age, performing heavy physical work (increased risk of lactic acidosis).

Pregnancy and lactation:The drug Formin Pliva is contraindicated for use during pregnancy and during breastfeeding.
When planning or developing a pregnancy, the drug Formin Pliva should be discontinued and insulin therapy should be prescribed. The patient should be warned about the need to inform the doctor if a pregnancy occurs. Mother and child should be monitored.
It is not known whether metformin with breast milk. If you need to use the drug Formin Pliva during lactation should stop breastfeeding.

Dosing and Administration:Inside, during or immediately after a meal. Tablets should be taken whole, not liquid and squeezed with a sufficient amount of liquid (200 ml of water).
Monotherapy and combination therapy with other oral hypoglycemic agents
The initial dose of 1 tablet (850 mg) 1 time per day in the evening. After 7-15 days, in the absence of adverse effects on the part of the gastrointestinal tract, 1 tablet (850 mg) is prescribed 2 times a day in the morning and in the evening. A further gradual increase in the dose is possible depending on the concentration of glucose in the blood.
The maintenance daily dose is 1700 mg / day. To reduce side effects from the GIT, the dose should be divided into 2 divided doses. The maximum daily dose is 2550 mg / day, divided into 3 doses.
In case of planning the transition to therapy with Formin Pliva from another hypoglycemic agent, stop taking another drug and start taking Plamin Pliva in the dose indicated above.
Combination with insulin
The drug Formin Pliva and insulin can be used as a combination therapy to achieve better glycemic control.
The drug Formin Pliva is taken in the usual initial dose - 850 mg 2-3 times a day. The dose of insulin is selected based on the results of determining the concentration of blood glucose.After 10-15 days, the dose is adjusted depending on the blood glucose concentration. The maximum daily dose of metformin for combined treatment is 1700 mg / day, divided into 2 doses.
In elderly patients, the daily dose should not exceed 850 mg / day.

Side effects:The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01% (including isolated cases).
From the central nervous system: often - a taste disorder (metallic taste in the mouth).
From the digestive system: very often - nausea, vomiting, abdominal pain, lack of appetite, diarrhea, flatulence that occur during the initial period of treatment and in most cases spontaneously passing; single cases - a violation of liver function indicators or hepatitis, completely disappearing after drug withdrawal.
Allergic reactions: very rarely - erythema, itchy skin, skin rash, hives.
From the side of metabolism: very rarely - lactic acidosis (requires withdrawal of the drug).
Other: very rarely - with prolonged use develops hypovitaminosis B12 (including megaloblastic anemia) and folic acid (impaired absorption).

Overdose:Symptoms. With the use of metformin in a dose of 85 g there was no hypoglycemia, but there was a development of lactic acidosis. The early symptoms of lactic acidosis are nausea, vomiting, diarrhea, lower body temperature, abdominal pain, muscle pain, there may be more rapid breathing, dizziness, impaired consciousness and coma development.
Treatment. In case of signs of lactic acidosis, metformin treatment should be stopped immediately, the patient urgently hospitalized and, having determined the concentration of lactate, clarify the diagnosis. The most effective measure for excretion from the body of lactate and metformin is hemodialysis. Conduct also symptomatic treatment.

Interaction:Contraindicated combinations
Radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis in diabetic patients on the background of functional renal failure.The use of metformin should be discontinued 48 hours before and not resumed earlier 48 hours after radiographic examination using radiopaque means.
Unrecommended combinations
With the simultaneous use of metformin with alcohol and ethanol containing drugs, the risk of developing lactic acidosis during acute alcohol intoxication increases, especially when fasting or following a low-calorie diet, as well as in liver failure.
Combinations that require caution when applying
With the simultaneous use of metformin with danazolom may develop hyperglycemic effect. If it is necessary to treat danazol and after stopping its intake, correction of the dose of metformin is required under the control of blood glucose concentration.
Chlorpromazine in high doses (100 mg / day) reduces the release of insulin and increases the concentration of glucose in the blood. When used simultaneously with neuroleptics and after stopping their intake, a dose adjustment of metformin is required under the control of glucose concentration.
During the study of the interaction of nifedipine and metformin, the administration of a single dose of nifedipine to healthy volunteers led to an increaseabsorption of metformin, as well as an increase in Cmax and AUC metformin in plasma by 20% and 9%, respectively, and an increase in the excretion of metformin in the urine. The time to reach Cmax and T1 / 2 did not change at the same time. The effect of metformin on the pharmacokinetics of nifedipine was minimal.
Angiotensin-converting enzyme inhibitors and other antihypertensive drugs can reduce the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.
With the simultaneous use of metformin with derivatives of sulfonylurea, insulin, acarbose and salicylates, an increase in hypoglycemic effect is possible.
When studying the interaction of metformin and glibenclamide in patients with type 2 diabetes mellitus, no significant changes in the pharmacokinetics / pharmacodynamics of metformin were observed. Metformin in general, reduced AUC and Cmax of glibenclamide in plasma, but this index varied greatly. For this reason, the clinical significance of this interaction remains unclear.
Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of decreased kidney function. In this case, care must be taken when applying metformin.
With the simultaneous use of "loop" diuretics and metformin, there is a risk of lactic acidosis because of the possible emergence of functional renal failure.
Furosemide increases Cmax and metformin AUC in plasma, respectively, by 22% and 15%, without significant changes in renal clearance of metformin. In its turn metformin reduces Cmax and AUC of furosemide in plasma by 31% and 12%, respectively, and T1 / 2 furosemide decreases by 32% without any significant changes in its renal clearance compared to the same parameters with furosemide monotherapy.
Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitadine, triamterene, trimethopril and vancomycin), the secretion of which is through the kidneys through tubular secretion, can theoretically interact, competing for common tubular transport systems in the kidneys. Cimetidine increases both Cmax of metformin in plasma, and its AUC by 60% and 40%, respectively. Metformin does not affect the pharmacokinetic parameters of cimetidine.
Some drugs can cause hyperglycemia and contribute to a decrease in the effectiveness of hypoglycemic agents.Such drugs include thiazides and other diuretics, GKO, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, a nicotinic acid, sympathomimetics, calcium antagonists and isoniazid. With the simultaneous use of these drugs with metformin or, on the contrary, in the event of their withdrawal, it is recommended to carefully monitor the effectiveness of metformin (its hypoglycemic effect) and, if necessary, adjust the dose of metformin.

Special instructions:During the period of treatment with the drug Formin Pliva, it is necessary to regularly monitor the concentration of glucose in the blood on an empty stomach and after eating.
The patient should be warned about the need to stop taking the drug Formin Pliva and see a doctor if there is vomiting, abdominal pain, muscle pain, general weakness and severe malaise. These symptoms may be a sign of lactic acidosis.
The Formin Pliva drug should be discontinued 48 hours before and during the 48 h period after the X-ray examination (including urography, intravenous angiography) using radiopaque means.
The Formin Pliva drug should be discontinued 48 hours before and during the 48 h postoperative period under general anesthesia, spinal or epidural anesthesia. Since the drug Plamin Plin is excreted by the kidneys, before starting treatment and regularly in the future should determine the CC in serum: in patients with preserved kidney function 1 time per year; in patients with reduced serum CK and in elderly patients - 2-4 times a year.
Caution should be exercised during the treatment with the Foramin Pliva prep with the kidney function, for example, during the initial period of therapy with antihypertensive agents, diuretics, NSAIDs.
It is necessary to inform the patient about the need to consult a doctor if symptoms of bronchopulmonary infection or infectious disease of the genito-urinary organs appear.
Against the background of the use of the drug Formin Pliva, one should abstain from drinking alcohol in connection with an increased risk of hypoglycemia and an antagonistic effect.
Hypovitaminosis B and when taking the drug Formina Pliva is caused by a violation of absorption and has a reversible character. When you cancel the drug Formin Pliva, the signs of hypovitaminosis B12 disappear quickly.

Effect on the ability to drive transp. cf. and fur:Monotherapy with Formin Pliva does not cause hypoglycemia and therefore does not affect the ability to drive and work with machinery. When using the drug Formin Pliva with other hypoglycemic agents (derivatives of sulfonylurea, insulin, etc.), it is possible to develop hypoglycemic conditions in which the ability to drive vehicles and engage in other potentially dangerous activities that require increased attention and rapid psychomotor reactions deteriorates.

Form release / dosage:Film-coated tablets 850 mg.

Packaging:For 10 tablets in a blister of PVC / PVDC / aluminum foil. For 3 or 6 blisters together with instructions for use in a cardboard box.

Storage conditions:At a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:4 years.
Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013733 / 01

Date of registration:31.08.2011

Expiration Date:Unlimited

The owner of the registration certificate:Pliva of Hrvatska dooPliva of Hrvatska doo Croatia

Manufacturer: & nbsp

PLIVA HRVATSKA, d.o.o. Croatia

Information update date: & nbsp2016-09-24

Illustrated instructions

Instructions

Formin Pliva (Formin Pliva)