UFT (UFT)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceTegafur + UracilTegafur + Uracil
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  • UFT
    capsules inwards 
    Merck KGaA     Germany
    • Dosage form: & nbspcapsules
    Composition:

    Each capsule contains:

    active substances: 224 mg of uracil and 100 mg of tegafur.

    Excipients: sodium lauryl sulfate and giprolose partial ether. Shell: titanium dioxide, gelatin

    Composition of ink: iron dye red oxide, carnauba wax, butanol, ethanol dehydrated, glyceryl monooleate.

    Description:Hard opaque gelatin capsules in white, size "2". The body and the lid have the inscription "TS 434". The contents of the capsules are granules and / or white powder.
    Pharmacotherapeutic group:antitumor drug, antimetabolite.
    ATX: & nbsp

    L.01.B.C.53   Tegafur in combination with other drugs

    Pharmacodynamics:

    UVT is an antitumor drug 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 (DPD), inhibiting the decomposition of 5-fluorouracil. Clinical effects of 5-FU are manifested by the action of its two active metabolites: 5-fluorodioxyridine monophosphate (FUDF), which suppresses the synthesis of DNA due to the formation of tertiary complexons with thymidylate synthetase and intracellular derivatives of folic acid, and 5-fluorouridine-triphosphate (FdUTP), which is incorporated into RNA and disrupts 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:

    After ingestion, the drug is rapidly absorbed. Maximum concentrations of tegafur, uracil and 5-fluorouracil are achieved after 1-2 hours.

    In the presence of foods high in fat, the area under the pharmacokinetic curve "concentration-time" (AUC) for uracil and 5-FU in plasma are reduced by 66% and 37%, respectively, compared with the use of UFT on an empty stomach. The concentrations of tegafur in plasma vary slightly. Values

    maximum concentrations of tegafur, uracil and 5-FU are reduced and the time to achieve them increases.

    After ingestion, absorption and excretion of tegafur and uracil follow monoexponential kinetics. The binding of tegafur with blood proteins is 52%, binding of uracil with blood proteins is negligible.

    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 partly as an isoenzyme of 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.

    Less than 20% of the drug is excreted in the urine unchanged. The half-life of tegafur and uracil after oral administration of the drug is 11 hours and 20-40 minutes, respectively. The three hydroxymetabolites of tegafur are excreted in the urine. Half-life S-tegafur (10.3 hours) is 4 times higher than half-life R- tegafur (2.4 hours).

    The concentration of uracil decreases rapidly after reaching the maximum concentration.

    The maximum concentrations of 5-FU are reached after 30-60 minutes (approximately 200 ng / ml) and remain detectable at a concentration of more than 1 ng / ml for 8 hours before the next dose of the drug.

    There was no noticeable cumulation of tegafur and uracil during the 28-day course of treatment with the drug.

    The maximum concentration and AUC tegafur in blood plasma increases 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. 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:UVT is shown as a first-line drug for the treatment of metastatic cancer of the colon and rectum in combination with calcium folinate.
    Contraindications:

    - Hypersensitivity to tegafur, uracil or any other ingredient included in the preparation.

    - Severe hepatic impairment

    - Inhibition of bone marrow function as a result of previously conducted radiation or chemotherapy

    - Confirmed deficiency of the isoenzyme of liver cytochrome CYP2A6

    - Confirmed deficiency of dihydropyrimidine dehydrogenase

    - Combination with inhibitor dihydropyrimidine dehydrogenase brivudine

    - Stomach ulcer and duodenal ulcer

    - Pregnancy and the period of breastfeeding.

    - Children under 18 years.

    Pregnancy and lactation:contraindicated
    Dosing and Administration:

    Standard treatment regimen: 300-600 mg of tegafur (3-6 capsules) divided into 2-3 doses. In combination with other antitumor drugs, dose adjustments are 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 from the surface area of ​​the body. Initial dose of tegafur 300 mg / m2/ day and uracil 672 mg / m2/day.The recommended dose of calcium folinate is 90 mg per day. UFT is taken concurrently with calcium folinate three times a day every 8 hours at least 1 hour before or 1 hour after meals. Drugs take 28 days, followed by a break of 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 (m2)

    number of capsules per day

    Mode of taking capsules

    morning

    afternoon

    evening

    <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 effects:

    On the part of the hematopoiesis system: The most severe is myelosuppression (anemia, leukopenia, thrombocytopenia). In very rare cases, pancytopenia and agranulocytosis develop.

    From the nervous system: drowsiness, impaired consciousness, insomnia, depression, paresthesia, lack of smell, extrapyramidal disorders, urinary incontinence, paralysis. limbs, speech disturbance, gait disturbance,

    GoalOvasion, memory impairment, leukoencephalopatand I.

    From the gastrointestinal tract: nausea, stomatitis, dry mouth, anorexia, heartburn, vomiting, abdominal pain, constipation, flatulence, flavors, gastritis, stomach and / or duodenal ulcer.The most severe are diarrhea, hemorrhagic, ischemic or necrotic enteritis, acute pancreatitis, severe violations of liver function, including fulminant hepatitis, liver cirrhosis.

    On the part of the respiratory system: interstitial pneumonia, cough

    From the cardiovascular system: Angina pectoris, arrhythmia, ischemia and infarction myocardium.

    From the urinary system: acute renal failure, nephrotic syndrome, urinary incontinence, anuria, hematuria.

    From the skin and subcutaneous appendages: alopecia, exfoliative dermatitis (palms and soles are especially sensitive), skin pigmentation disorder, rash, itching, crabiensa, increased photosensitivity, discoid rashes, reminiscent of systemic lupus erythematosus, changes in the structure of the nails.

    Overdose:

    In case of an overdose, if the patient is conscious, vomiting or rinsing of the stomach should be performed. It is necessary to establish strict control over the patient and in particular for the function of hematopoiesis and functional tests of the liver. The specific antidote to UFT is unknown. Treatment is symptomatic.

    Interaction:

    Calcium folinate, as a biomodulator, is able to enhance the antitumor effect of fluorouracil by stabilizing the complexone of thymidylate synthetase and FdUMF by forming the intracellular metabolite of 5,10-methylenetetrahydrofolate. Calcium folinate with simultaneous administration with the drug, UVT does not significantly affect the pharmacokinetics of tegafur, uracil and 5-fluorouracil.

    Tegafur is partially metabolized by cytochrome isoenzyme CYP2A6. Therefore, UFT should be used with caution in combination with substrates or inhibitors of this enzyme - coumarin derivatives, methoxalen, clotrimazole, ketoconazole, miconazole.

    The simultaneous use of UVT with drugs that inhibit the enzyme DPD, responsible for the catabolism of endogenous and fluorinated pyrimidines (for example, brivudine) significantly increases the toxicity of the drug UFT.

    Special instructions:

    During treatment with UFT, patients should be closely monitored. It is necessary to conduct blood tests and check the function of the liver.

    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 before the restoration of granulocytes 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.

    Due to the toxicity of UVT together with drugs suppressing the enzyme DPD, a break before taking the drug UFT to restore the activity of endogenous and fluorinated pyrimidines is necessary.

    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, yellowing of the sclera (jaundice). If symptoms of a liver function disorder appear, stop taking UFT and prescribe the appropriate treatment.

    If symptoms of central nervous system disorders appear, discontinue treatment with UFT.

    In patients older than 65 years, side effects such as anemia, diarrhea and inflammation of the mucous membranes of the gastrointestinal tract are somewhat more frequent.

    Form release / dosage:

    Aluminum / PVC blister for 12 capsules in a blister pack of 3 or 10 blisters in a package together with instructions for use in a cardboard pack.

    Packaging:(12) - packings cellular planimetric (10) - packs cardboard
    (12) - packings, cellular planimetric (3) - packs cardboard
    (120) - polypropylene containers (1) - cardboard packs
    (28) - polypropylene containers (1) - cardboard packs
    Storage conditions:

    List B.

    Store at a temperature not exceeding 25 ° C.

    Shelf life:

    2 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015164 / 01
    Date of registration:14.01.2009
    The owner of the registration certificate:Merck KGaAMerck KGaA Germany
    Manufacturer: & nbsp
    Representation: & nbspPHARMONYX PHARMONYX Russia
    Information update date: & nbsp13.09.2015
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