Petromatrix

Active material: uracil, Tegafur
When ATH: L01BC53
CCF: Anticancer drug
ICD-10 codes (testimony): C16, C18, C19, C20, C22, C23, C25, (C) 49.0, C50, C53, C67
When CSF: 22.02.03.01
Manufacturer: MERCK KGaA (Germany)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, white, opaque; on and looked just like the housing – marking “TC 434”, light brown.

Excipients: sodium lauryl, hydroksypropyltsellyuloza.

28 PC. – plastic bags (1) – polypropylene containers (1) – cardboard boxes.
120 PC. – plastic bags (1) – polypropylene containers (1) – cardboard boxes.

Pharmacological action

Anticancer drug, contains tegafurum and uracil in molar ratio 1:4.

In the body tegafurum is transformed into active metabolite 5-fluorouracil (5-FU), with antitumor activity. Uracil is a competitive inhibitor of digidropirimidindegidrogenazy (DPD), preventing the destruction of 5-FU.

Clinical effects of 5-fluorouracil manifested its two active metabolites: 5-ftordioksiuridin monophosphate (FdUMF), that inhibits DNA synthesis through education tertiary chelating agents with timidilatsintetazoj and intracellular folic acid derivatives, and 5-ftoruridin-triphosphate (FdUTF), that is included in the RNA and violates its function.

Thanks to the overwhelming effects of uracil to DPD concentration of 5-FU, metabolite of teghafur, in the plasma increases.

Pharmacokinetics

Absorption

After intake of rapidly absorbed active substances. C_max teghafur, uracil and 5-FU achieved through 1-2 no. Uracil concentration after reaching C_max rapidly declining.

In the presence of food with high fat indicator AUC for uracil and 5-FU in plasma by 66% and 37% respectively, compared with the reception of prandial UFT. Teghafur concentration in plasma is changed slightly. The Values Of C_max teghafur, uracil and 5-FU reduced and time to achieve them is increased.

C_max 5-FU is 200 ng / ml, achieved through 30-60 mines and remains defined in a concentration of more than 1 ng / ml for 8 h before taking the next dose of the drug.

C_max and AUC of teghafur in plasma increases in proportion to the adopted inside dose (from 100 mg 400 mg). Concentrations of uracil and 5-FU in plasma increases more than proportionally with the dose.

Intake intake and excretion of uracil and teghafur follow monojeksponencial'noj kinetics.

Distribution

Linking blood protein is teghafur 52%, linking blood protein uracil is negligible.

Metabolism

The transformation of teghafur into 5-FU comes through with-5'okislenija (mikrosomaiona enzymes) and hydrolysis of p-2 '(enzymes in cytosol). Mikrosomalnoe oxidation teghafur is partly cytochrome CYP2A6. Enzymes in cytosol, responsible for the metabolism of teghafur, remain unknown. Metabolism of 5-FU occurs along the path of natural pyrimidine degradation – uracil.

Deduction

Less 20% the drug is excreted in urine as unchanged. T_1/2 teghafur and uracil after taking the drug inside make up 11 and h 20-40 min, respectively. Three gidroksimetabolita teghafur are excreted in the urine. T_1/2 S-teghafur (10.3 no) in 4 times T_1/2 R-teghafur (2.4 no).

Notable cumulation and teghafur uracil during 28 day course of drug treatment were observed.

Pharmacokinetics in special clinical situations

Drug metabolism occurs mainly in the liver, Therefore, violations of the kidneys will not have a significant impact on drug UFT farmakokinetiku.

Testimony

— treatment of metastatic cancer of the colon and rectum as a first line drug in combination with calcium folinatom;

— treatment of breast tumors, stomach, Head and Neck, liver, gallbladder, Biliary, pancreas, the bladder and cervix.

Dosage regimen

Standard treatment scheme: 300-600 mg teghafur (3-6 caps.), divided by 2-3 admission. In combination with other drugs protivoopujolevami dose adjustment is not required UFT. UFT dose may increase or decrease depending on the acceptability of the drug patients. Daily dose should not exceed teghafur 600 mg.

When combined with calcium folinatom dosage UFT is calculated on the basis of body surface area. The initial dose teghafur 300 mg / m²/day and uracil 672 mg / m²/d. The recommended dose of calcium folinata 90 mg / day. UFT take simultaneously with calcium folinatom 3 times per day every 8 h, at least 1 hours before or after 1 hours after meals. Take medications 28 days, then you should break – 7 days. The total duration of one course – 35 days.

Receive mode and daily doses of the drug UFT are represented in table:

Side effect

From the hematopoietic system: mielosuprescia (anemia, leukopenia, thrombocytopenia); In very rare cases – pancytopenia and agranulocytosis.

From the central and peripheral nervous system: drowsiness, disturbance of consciousness, insomnia, depression, paraesthesia, extrapyramidal disorder, urinary incontinence, paralysis of limbs, speech disorder, gait disturbance, dizziness, memory impairment, lejkojencefalopatija.

From the digestive system: nausea, stomatitis, dry mouth, anorexia, heartburn, vomiting, abdominal pains, constipation, flatulence, lack of sense of smell, flavor violation, gastritis, izgyazwlenia mucous membrane stomach and/or duodenal ulcer; the most severe are diarrhea, hemorrhagic, Ischemic or necrotic enteritis, acute pancreatitis, severe liver, including ful'minantnyj hepatitis, cirrhosis of the liver.

The respiratory system: interstitial pneumonia, cough.

Cardio-vascular system: angina, arrhythmia, ischemia and myocardial infarction.

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

Dermatological reactions: alopecia, formation of blisters and dermatitis (particularly sensitive hands and feet), violation of skin pigmentation, rash, itch, hives, increased photosensitivity, diskoidnye precipitation, resembling SLE, changes in the structure of nails.

Contraindications

- Severe liver;

— oppression of bone marrow as a result of past radiation or chemotherapy;

is a confirmed deficit CYP2A6 CYP;

- Gastric ulcer and duodenal ulcer;

- Pregnancy;

- Lactation (breast-feeding);

- Childhood and adolescence up 18 years;

-hypersensitivity to tegafuru, uracil or any other ingredient, part of the drug.

Pregnancy and lactation

Use of the drug is contraindicated in pregnancy and lactation.

Cautions

Application of UFT should be carried out under the supervision of a physician. You should periodically review the blood and liver function.

With negematologicheskoj drug toxicity recommended reducing the daily dosage for 1 capsule throughout the remainder of the course of treatment.

In case of manifestation of hematological toxicity of the drug, the course of treatment with UFT and calcium folinate preparations is interrupted until granulocytes are restored to a level of at least 1500 / μl and platelets to a level of at least 100,000 / μl. Dose of the drug UFT in the repeated course will be reduced by 1 capsule.

When you change the dosage UFT dose calcium folinata does not change.

DPD deficiency risk increases drug toxicity.

Abdominal pain and / or diarrhea may be the first signs of severe enteritis.. When they appear, treatment with the drug should be discontinued..

Liver symptoms are loss of appetite, Yellow staining skler eye (jaundice). If symptoms of liver dysfunction appear, it is necessary to stop taking UVT and prescribe appropriate treatment.

When symptoms of CNS violations should stop treatment with UFT.

Patients over the age of 65 years, several more commonly seen side effects such, as anemia, diarrhea and inflammation of the mucous membranes of the gastrointestinal tract.

Overdose

Treatment: if the patient is conscious, induce vomiting or gastric lavage; medical supervision of the patient should be established and the hematopoiesis function and liver function tests should be monitored. Treatment of symptomatic. The specific antidote to UVT is unknown.

Drug Interactions

Calcium folinate, as a biomodulator, is able to enhance the antitumor effect of 5-FU by stabilizing the complexone thymidylate synthetase and FdUMF due to the formation of an intracellular metabolite of 5,10-methylenetetrahydrofolate. Calcium folinate, when taken simultaneously with UVT, does not significantly affect the pharmacokinetics of tegafur, uracil and 5-fluorouracil.

You should not take UVT concurrently with medications (eg, halogenated), inhibiting the enzyme DPD (dihydropyrimidine dehydrogenase), responsible for the catabolism of endogenous and fluorinated pyrimidines. At the same time, the risk of UVT toxicity increases significantly.

Tegafur is partially metabolized by the CYP2A6 isoenzyme. Therefore, UVT should be used with caution in combination with substrates or inhibitors of this enzyme.: coumarin, methoxypsoralene, clotrimazole, ketoconazole, miconazole.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in protected from light., inaccessible to children at temperature from 15 ° to 30 ° C. Shelf life – 42 Months.