Варфарекс®
Producer: AS Grindex (JSC Grindeks) Latvia
Code of automatic telephone exchange: B01AA03
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active ingredient: 1, 3 and 5 mg of warfarin of sodium (in the form of a clathrate).
Excipients: lactose, cellulose microcrystallic, кросповидон, magnesium stearate; dyes: indigo carmine, Ponso's dye 4R.
Drug of anticoagulating action.
Pharmacological properties:
Pharmacodynamics. Anticoagulant of indirect action. Vitamin of K-dependent blood-coagulation factors suppresses synthesis (II, VII, IX and X) and proteins C and S in a liver. Варфарекс does not exert impact on already created blood clots, but interferes with their increase and prevents formation of new blood clots.
Pharmacokinetics. Drug is racemic mix of R and S stereoisomers. Stereoisomer S is 2-5 times more active than stereoisomer R, but its action is less long.
Absorption. After intake warfarin is completely absorbed from a GIT. Cmax in a blood plasma is reached in 4 h after reception. Therapeutic concentration in a blood plasma makes about 1-5 mkg/ml (0.003-0.015 mmol/l).
Distribution. Linkng with proteins of plasma - 97-99%.
Metabolism. Warfarin is exposed to metabolism with the participation of microsomal enzymes of a liver with formation of low-active and inactive metabolites.
Removal. Metabolites are removed with urine and in a small amount - with bile. After a single dose of drug in T1/2 makes 20-60 h (on average 40 h). 92% of the accepted dose are removed with urine in the form of metabolites and only the minimum quantity - in not changed look.
Pharmacokinetics in special clinical cases. Essential changes of pharmacokinetics of Varfareks at patients of advanced age are not observed. It is established that patients of this group are more sensitive to anticoagulants, however the nature of this phenomenon is not found out.
At abnormal liver functions synthesis of blood-coagulation factors decreases, and Varfareks's (warfarin) metabolism is slowed down that leads to strengthening of its braking influence on a blood coagulation.
Indications to use:
Prevention and treatment of the diseases caused by formation of blood clots:
— thromboembolism of lungs;
— atrial fibrillation;
— myocardial infarction;
— at prosthetics of valves of heart.
Route of administration and doses:
The dose, frequency of reception and duration of treatment are established individually, taking into account disease severity and results of control of a blood coagulation (MNO value). The patient should not change a drug dose independently.
Варфарекс accept in 1 times/days, preferably at the same time.
In an initiation of treatment of Varfareks usually appoint in a dose 2.5-5 mg/days during the first 2 days, gradually selecting a dose according to individual reaction of a blood coagulation (for MNO value). After achievement of the MNO desirable value (2-3, and in some cases 3-4.5) drug is appointed in a maintenance dose.
To the patients of advanced age weakened or relating drug to risk group appoint in lower initial dose and are careful at its increase.
In an initiation of treatment laboratory control of MNO is exercised every day, within the next 3-4 weeks control is exercised by 1-2 times a week, later - each 1-4 weeks. More frequent additional control is necessary when the state of health of the patient changes, before planned operation or other procedure and also when appoint or cancel any other medicine.
Features of use:
Use of anticoagulants increases risk of development of bleedings. During treatment by Varfareks it is necessary to carry out regular control of a condition of coagulant system of blood. To be extremely attentive with the acute and cutting objects, in avoidance of wounds and emergence of krovotechniya.
At Varfareks's use in combination with the drugs strengthening his action it is necessary to control MNO at the beginning and at the end of treatment, whenever possible, in 2-3 weeks from the beginning of therapy. At use of drugs which can increase risk of development of bleeding because of decrease in normal coagulation (inhibition of blood-coagulation factors or activity of enzymes of a liver) the strategy of anticoagulating therapy has to be defined by a possibility of carrying out laboratory control. If frequent laboratory control is possible, then in need of therapy by similar means Varfareks's dose can be reduced by 5-10%. If carrying out laboratory control is complicated, then treatment by Varfareks it is necessary to stop in case of need purposes of the specified drugs.
The patient should be warned about need of the address to the doctor at development against the background of therapy of the disturbances of digestion which are followed by diarrhea, fever; to report about Varfareks's reception to other doctor, the stomatologist, the druggist; the careful address with sharp and dangerous objects to avoid the activity connected with risk of wound and the subsequent bleeding; not to accept any vitamins or dietary supplement without consultation of the doctor; to receive the normal balanced food, without changing its character too sharply.
During treatment it is necessary to abstain from alcohol intake (risk of development of a prothrombinopenia).
In need of use for patients with a lactose intolerance it must be kept in mind that one tablet of Varfareks contains 106-112 mg of lactose.
Safety of use of drug for children in clinical trials it is studied insufficiently.
Data on adverse influence of Varfareks on ability to manage vehicles and to service other mechanisms are absent.
Drug is contraindicated at a renal failure of heavy degree.
Drug is contraindicated at a heavy liver failure.
Drug is contraindicated to use at pregnancy.
Women of childbearing age during treatment should use effective methods of contraception.
Warfarin in insignificant quantities is removed with breast milk and practically does not exert impact on coagulability of blood at the child therefore drug can be used in the period of a lactation, at the same time it is recommended to refrain from breastfeeding in the first days of therapy by warfarin.
Side effects:
From coagulant system of blood: most often - bleedings and hemorrhages in various bodies and fabrics.
From cardiovascular system: in some cases - disturbance of blood circulation in extremities or in internals. Blood circulation disturbance is demonstrated most often by pains and dark red skin color of toes.
From the alimentary system: seldom - nausea, vomiting, diarrhea, abdominal pains, an abnormal liver function (increase in activity of liver enzymes, jaundice).
Allergic reactions: itch, urticaria, dermatitis.
Others: fever, general weakness, change of a picture of peripheral blood, passing alopecia.
Interaction with other medicines:
Varfareks's efficiency can change under the influence of many medicines.
Varfareks's action amplifies at its simultaneous use with Allopyrinolum, Amiodaronum, anabolic steroids (alkylated in situation C-17), acetylsalicylic acid and other NPVS, with heparin, glibenclamide, a glucagon, danazoly, diazoxide, Disopyramidum, Disulfiramum, an isoniazid, ketokonazoly, klaritromitsiny, Clofibratum, levamisole, metronidazole, Miconazolum, Acidum nalidixicum, nilutamidy, omeprazoly, paroksetiny, proguanil, peroral hypoglycemic means - sulphonylurea derivatives, streptocides, with Tamoxifenum, thyroxine, quinine, quinidine, fluvoksaminy, flukonazoly, ftoruratsily, hinolona, Chlorali hydras, chloramphenicol, cephalosporins, Cimetidinum, erythromycin, Acidum etacrynicum, ethanol.
NPVS, Dipiridamolum, valproic acid, inhibitors of isoenzymes of P450 cytochrome, Cimetidinum, chloramphenicol, purgatives increase risk of development of bleedings. It is necessary to avoid the combined use of these drugs and Varfareks (Cimetidinum can be replaced with ranitidine or famotidine). In need of purpose of chloramphenicol anticoagulating therapy can be stopped temporarily.
Diuretics can reduce effect of anticoagulants (in case of the expressed hypovolemic action which can lead to increase in maintenance of factors of coagulation).
Varfareks's action is weakened at its simultaneous use with barbiturates, vitamin K, glutetimidy, griseofulvin, dikloksatsilliny, carbamazepine, mianseriny, paracetamol, retinoids, rifampicin, sukralfaty, phenazone, Colestyraminum.
High content of vitamin K in food stuffs (spinach, broccoli, salad or other deciduous vegetables) can reduce Varfareks's efficiency. Smoking can reduce anticoagulative effect of drug also.
Contraindications:
— bleeding or threat of development of bleeding at some serious illness;
— heavy liver failure;
— obturatsionny jaundice;
— renal failure of heavy degree;
— acute IDCS;
— deficit of proteins C and S;
— a peptic ulcer of a stomach and duodenum in an aggravation phase;
— stroke;
— alcoholism;
— heavy arterial hypertension;
— recently undergone or alleged difficult operations and diagnostic procedures;
— children's age;
— pregnancy;
— insufficient opportunities for assessment of a condition of coagulant system of blood by means of laboratory methods;
— hypersensitivity to drug components.
Overdose:
Carry to symptoms of overdose: an odontorrhagia, nasal bleeding, excessively plentiful menstrual bleeding, severe or long bleeding at small superficial damages, hemorrhages in skin, availability of blood in urine or Calais, and also other symptoms of bleeding.
If the prothrombin time makes more than 5% and there are no other possible bleeding points (for example, нефроуролитиаз), correction of the mode of dosing is not required. At insignificant bleedings it is necessary to reduce a dose of drug and to stop treatment for short term.
In case of development of heavy bleeding appoint vitamin K before recovery of koagulyantny activity. At the menacing bleedings - transfusion of concentrates of factors of a prothrombin complex, freshly frozen plasma or whole blood.
Storage conditions:
To store in the place, dark and unavailable to children, at a temperature not above 25 degrees Celsius.
Issue conditions:
According to the recipe
Packaging:
Tablets on 30 or 100 pieces in densely corked platsmassovy bottles with a cover. On 1 bottle in cardboard packaging.
