Universal reference book for medicines
Product name: UFT (UFT)

Active substance: non-appropriated, tegafur

Type: Antitumor preparation

Manufacturer: MERCK (Germany) manufactured by TAIHO PHARMACEUTICAL (Japan)
Composition, form of production and packaging
Capsules hard gelatinous, white, opaque; on the cover and body - marking "TC 434", light brown color.
1 caps.
tegafur 100 mg
uracil 224 mg
Excipients: sodium lauryl sulfate, hydroxypropylcellulose.
28 pcs. - polyethylene bags (1) - polypropylene containers (1) - cardboard boxes.
120 pcs. - polyethylene bags (1) - polypropylene containers (1) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
An antineoplastic preparation containing tegafur and uracil in a molar ratio of 1: 4.
In the body, tegafur is transformed into an active metabolite of 5-fluorouracil (5-FU), which has an antitumor effect. Uracil is a competitive inhibitor of dihydropyrimidine dehydrogenase (DPD), which prevents the destruction of 5-FU.
Clinical effects of 5-fluorouracil are manifested by the action of its two active metabolites: 5-fluorodioxyridine monophosphate (FdUMF), which suppresses the synthesis of DNA by the formation of tertiary complexons with thymidylate synthetase and intracellular folic acid derivatives, and 5-fluorouridine tri-phosphate (FUDF), which is included in RNA and violates its function.
Due to the suppressive effect of uracil on DPD, the concentration of 5-FU, the tegafur metabolite, in the plasma is increased.
PHARMACOKINETICS
Suction
After ingestion, the active substances are rapidly absorbed. C max tegafur, uracil and 5-FU are achieved after 1-2 hours. The concentration of uracil after reaching Cmax rapidly decreases.
In the presence of high-fat foods, the AUC for uracil and 5-FU in plasma are reduced by 66% and 37%, respectively, compared with fasting fasting drug. The concentrations of tegafur in plasma vary slightly. The C max values ​​of tegafur, uracil and 5-FU decrease and the time of their attainment increases.
Cmax 5-FU is 200 ng / ml, achieved after 30-60 min and remains detectable at a concentration of more than 1 ng / ml for 8 hours before the next dose of the drug.
Cmax and AUC of tegafur in blood plasma increase in proportion to the increase in oral dose (from 100 mg to 400 mg). The concentrations of uracil and 5-FU in the blood plasma increase more than proportionally to the dose.
After ingestion, absorption and excretion of tegafur and uracil follow monoexponential kinetics.
Distribution
The binding of tegafur with blood proteins is 52%, binding of uracil with blood proteins is negligible.
Metabolism
The transformation of tegafur into 5-FU is due to C-5'oxidation (microsomal enzymes) and hydrolysis of C-2 '(cytosol enzymes). Microsomal oxidation of tegafur occurs in part by cytochrome CYP2A6. The cytosol enzymes responsible for the metabolism of tegafur remain unknown. Metabolism 5-FU occurs along the path of degradation of natural pyrimidine - uracil.
Excretion
Less than 20% of the drug is excreted in the urine unchanged. T 1/2 tegafur and uracil after taking the drug inside are 11 hours and 20-40 minutes, respectively. The three hydroxymetabolites of tegafur are excreted in the urine. T 1/2 S-tegafur (10.3 h) is 4 times higher than T 1/2 R-tegafur (2.4 h).
There was no noticeable cumulation of tegafur and uracil during the 28-day course of treatment with the drug.
Pharmacokinetics in special clinical cases
Metabolism of the drug occurs mainly in the liver, therefore, renal dysfunction will not have a significant effect on the pharmacokinetics of the drug UFT.
INDICATIONS
- treatment of metastatic cancer of the colon and rectum as a first-line preparation in combination with calcium folinate;
- Treatment of tumors of the mammary gland, stomach, head and neck, liver, gall bladder, bile duct, pancreas, bladder and cervix.
DOSING MODE
Standard treatment regimen: 300-600 mg of tegafur (3-6 caps.), Divided into 2-3 doses. In combination with other antitumor drugs, dose adjustment of UFT is not required. The dose of UFT may increase or decrease, depending on the tolerability of the drug to patients. The daily dose of tegafur should not exceed 600 mg.
When combined with calcium folinate, the dose of UFT is calculated based on the surface area of ​​the body. The initial dose of tegafur 300 mg / m 2 / day and uracil 672 mg / m 2 / day. The recommended dose of calcium folinata is 90 mg / day. UFT is taken simultaneously with calcium folinate 3 times / day every 8 hours at least 1 hour before or 1 hour after meals. Drugs take 28 days, followed by a break - 7 days. The total duration of one course is 35 days.
The regimen of reception and daily doses of the drug UFT are presented in the table:
Body surface area (m 2 ) Number of capsules / day Capsule administration mode
in the morning in the afternoon
<1.17 3 1 1 1
1.17-1.49 4 2 1 1
1.50-1.83 5 2 2 1
> 1.83 6 2 2 2
SIDE EFFECT
On the part of the hemopoietic system: myelosuppression (anemia, leukopenia, thrombocytopenia); in very rare cases - pancytopenia and agranulocytosis.
From the side of the central nervous system and peripheral nervous system : drowsiness, impaired consciousness, insomnia, depression, parasthesia, extrapyramidal disorders, urinary incontinence, paralysis of limbs, speech impairment, gait disturbance, dizziness, memory impairment, leukoencephalopathy.
From the digestive system: nausea, stomatitis, dry mouth, anorexia, heartburn, vomiting, abdominal pain, constipation, flatulence, lack of smell, taste disorders, gastritis, ulceration of the stomach and / or duodenal ulcers; the most severe are diarrhea, hemorrhagic, ischemic or necrotic enteritis, acute pancreatitis, severe violations of liver function, including fulminant hepatitis, cirrhosis.
On the part of the respiratory system: interstitial pneumonia, cough.
From the cardiovascular system : angina, arrhythmia, ischemia and myocardial infarction.
From the urinary system : acute renal failure, nephrotic syndrome, anuria, hematuria.
Dermatological reactions: alopecia, blistering and dermatitis (palms and feet are especially sensitive), skin pigmentation disorder, rash, itching, urticaria, increased photosensitivity, discoid rashes resembling SLE, changes in the structure of the nails.
CONTRAINDICATIONS
severe hepatic impairment;
- oppression of bone marrow function as a result of previously conducted radiation or chemotherapy;
- confirmed deficiency of the isoenzyme CYP2A6;
- Stomach ulcer and duodenal ulcer;
- Pregnancy;
- the period of lactation (breastfeeding);
- children and adolescence under 18;
- hypersensitivity to tegafur, uracil or any other ingredient included in the preparation.
PREGNANCY AND LACTATION
The use of the drug is contraindicated in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Metabolism of the drug occurs mainly in the liver, therefore, renal dysfunction will not have a significant effect on the pharmacokinetics of the drug UFT.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
contraindication: marked violations of the liver. If symptoms of a liver function disorder appear, stop taking UFT and prescribe the appropriate treatment.
APPLICATION FOR CHILDREN
The drug is contraindicated in children and adolescents under 18 years.
SPECIAL INSTRUCTIONS
The use of the drug UFT should be carried out under the supervision of a doctor. Periodically, a blood test and liver function should be performed.
When developing non-hematologic toxicity of the drug, it is recommended to reduce the daily dose of the drug by 1 capsule throughout the remaining course of treatment.
When the hematological toxicity of the drug manifests, the course of treatment with UFT and calcium folinate is interrupted until the granulocyte is restored to a level of at least 1500 / μl and platelets to a level of at least 100,000 / μl. The dose of the drug UFT in the repeated course should be reduced by 1 capsule.
When changing the dose of the drug UFT dose of calcium folinata does not change.
When the DPD is deficient, the risk of drug toxicity increases.
Abdominal pain and / or diarrhea can serve as the first signs of the development of severe enteritis. When they appear, the drug should be discontinued.
Symptoms of liver dysfunction are loss of appetite, yellow eye sclera (jaundice). If symptoms of a liver function disorder appear, stop taking UFT and prescribe the appropriate treatment.
When symptoms of CNS disorders appear, discontinue treatment with UFT.
Patients over the age of 65 are more likely to experience side effects such as anemia, diarrhea, and inflammation of the gastrointestinal mucosa.
OVERDOSE
Treatment: if the patient is conscious, vomiting or rinsing of the stomach should be performed; it is necessary to establish medical supervision of the patient and to monitor the function of hematopoiesis and functional liver samples. Treatment is symptomatic. The specific antidote to UFT is unknown.
DRUG INTERACTION
Calcium folinate, as a biomodulator, is able to enhance the antitumor effect of 5-FU by stabilizing the complexone of thymidylate synthetase and FdUMF by forming the intracellular metabolite of 5,10-methylenetetrahydrofolate. Calcium folinate with simultaneous admission with the drug UFT does not have a significant effect on the pharmacokinetics of tegafur, uracil and 5-fluorouracil.
Do not take UF simultaneously with drugs (eg, halide), inhibiting the enzyme dihydropyrimidine dehydrogenase, responsible for the catabolism of endogenous and fluorinated pyrimidines. At the same time, the risk of toxicity of UFT increases significantly.
Tegafur is partially metabolized by the CYP2A6 isoenzyme. Therefore, UFT should be used with caution in combination with substrates or inhibitors of this enzyme: coumarin, methoxypsoralen, clotrimazole, ketoconazole, miconazole.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a protected from light, out of reach of children at a temperature of 15 ° to 30 ° C. Shelf life - 42 months.
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