Ftorafur^® (Capsules) Instructions for Use

Marketing Authorization Holder

Grindeks, JSC (Latvia)

Contact Information

Grindeks, JSC (Latvia)

ATC Code

L01BC03 (Tegafur)

Active Substance

Tegafur (Rec.INN registered by WHO)

Dosage Form

Ftorafur®

Capsules 400 mg: 100 pcs.

Dosage Form, Packaging, and Composition

Capsules hard gelatin, size No. 0, with a yellow body and an orange cap; the contents of the capsules are a white powder, odorless.

Excipients: stearic acid – 4 mg.

Composition of the capsule body titanium dioxide (E171) – 2%, quinoline yellow (E104) – 0.7139%, iron oxide red (E172) – 0.0057%, gelatin – up to 100%.
Composition of the capsule cap titanium dioxide (E171) – 2.5%, quinoline yellow (E104) – 0.1586%, ponceau 4R (E124) – 0.1983%, gelatin – up to 100%.

100 pcs. – polyethylene jars with a capacity of 150 ml (1) – cardboard boxes.

Clinical-Pharmacological Group

Antitumor drug. Antimetabolite

Pharmacotherapeutic Group

Antineoplastic agent, antimetabolite

Pharmacological Action

Antitumor action is due to the disruption of DNA and RNA synthesis. The fluorouracil formed as a result of hydrolysis inhibits the enzyme thymidylate synthase and DNA synthesis, incorporates into the RNA structure instead of uracil, making it defective, and inhibits cell proliferation.

In tumor cells, it is converted into 5-fluorodeoxyuridine-5-monophosphate, which is then phosphorylated into triphosphate and incorporated into RNA, and into floxuridine monophosphate, which inhibits thymidylate synthase. It is less toxic and better tolerated by patients than 5-fluorouracil.

Pharmacokinetics

Absorption

When taken orally, Tegafur is rapidly absorbed from the gastrointestinal tract and is detected in the blood for at least 24 hours after a single use. C_max of tegafur in blood plasma is reached within 4-6 hours after administration. Bioavailability is almost complete.

Distribution

It has high lipophilicity (200 times higher than fluorouracil), while remaining a water-soluble compound. High lipophilicity ensures rapid passage through biological membranes, distribution in the body, and penetration through the blood-brain barrier.

Metabolism

It is metabolized in the liver with the formation of metabolites, among which the pharmacologically active 5-fluorouracil plays a central role. Bioactivation occurs not only in the liver but can also be local in tumor tissue, which is characterized by an increased content of cytosolic hydrolytic enzymes.

Indications

• Colon and rectal cancer;
• Stomach cancer;
• Breast cancer;
• Atopic dermatitis;
• Cutaneous lymphomas.

ICD codes

Dosage Regimen

Administer Ftorafur^® orally. Calculate the daily dose based on 20-30 mg per kg of body weight.

Divide the total daily dose into 2-4 separate administrations. Do not exceed a maximum daily dose of 2 grams (2000 mg).

The total course dose is 30-40 grams. Maintain an interval of 4 weeks between treatment courses.

Reduce the dosage for elderly patients and for patients in the late stages of disease.

Take capsules with a sufficient amount of water. Adhere strictly to the prescribed schedule to maintain consistent drug levels.

Regularly monitor blood counts and liver and kidney function before and during therapy. Adjust or interrupt treatment based on laboratory results and clinical tolerance.

Discontinue use immediately upon appearance of stomatitis, pharyngitis, esophagitis, gastrointestinal bleeding, leukopenia, neutropenia, or thrombocytopenia.

Adverse Reactions

From the hematopoietic system leukopenia, neutropenia, thrombocytopenia, anemia.

From the digestive system nausea, vomiting, anorexia, abdominal pain, diarrhea, stomatitis, esophagitis, ulceration of the gastrointestinal mucosa, gastrointestinal bleeding, impaired liver function, acute hepatitis, acute pancreatitis.

From the nervous system dizziness, confusion, drowsiness, ataxia, euphoria, symptoms of leukoencephalitis.

From the cardiovascular system cardialgia, angina pectoris, myocardial ischemia, myocardial infarction.

From the organ of vision diplopia, lacrimation, fibrosis of the lacrimal ducts.

From the skin and subcutaneous tissues alopecia, impaired regeneration of the skin and nails.

Other pharyngitis, allergic reactions (including anaphylactic shock), impaired renal function, dehydration, interstitial pneumonia, loss of smell.

Contraindications

• Terminal stage of the disease;
• Acute profuse bleeding;
• Severe impairment of liver and/or kidney function;
• Leukopenia (less than 3000/µl);
• Neutropenia (less than 1000/µl);
• Thrombocytopenia (less than 100,000/µl);
• Anemia (hemoglobin level less than 65 g/l);
• Gastric and duodenal ulcer;
• Infectious diseases;
• Risk of developing gastrointestinal bleeding;
• Pregnancy;
• Lactation period (breastfeeding);
• Age under 18 years (efficacy and safety have not been proven);
• Hypersensitivity to the components of the drug.

With caution the drug should be used in patients with impaired hematopoiesis, mild to moderate impairment of liver and kidney function, as well as with impaired glucose metabolism.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

With caution the drug should be used in patients with mild to moderate liver dysfunction.

Use in Renal Impairment

Contraindicated in severe renal impairment.

With caution the drug should be used in patients with mild to moderate renal impairment.

Pediatric Use

The use of the drug is contraindicated under the age of 18 years (efficacy and safety have not been proven).

Geriatric Use

The dose of the drug can be reduced in elderly patients.

Special Precautions

Blood counts, functional state of the liver and kidneys should be monitored regularly.

With prolonged use of the drug, its side effects increase.

It should be borne in mind that the drug suppresses the patient’s reproductive function.

Dizziness, nausea and vomiting are reduced by dividing the daily dose into several doses.

If serious adverse events develop, it is necessary to stop using the drug.

The use of the drug should be stopped immediately if at least one of the following signs appears: stomatitis, pharyngitis, esophagitis, bleeding, leukopenia (less than 3000/µl), neutropenia (less than 1000/µl), thrombocytopenia (less than 100,000/µl). The effect on hematopoiesis may appear even 8-14 days after the end of treatment.

During treatment, careful oral care is necessary.

Use in pediatrics

The safety of the drug in children has not been studied.

Effect on the ability to drive vehicles and mechanisms

There have been no reports of an adverse effect of Ftorafur^® on the ability to drive a car and work with mechanisms. However, if such side effects as dizziness and drowsiness occur during the use of the drug, you should not drive a car and perform work that requires special attention and quick reactions.

Overdose

Symptoms increased toxic effects from the gastrointestinal tract, central nervous system and inhibition of hematopoiesis.

Treatment monitoring of hematopoietic function for at least 4 weeks, if necessary, symptomatic therapy is carried out. A specific antidote for tegafur is unknown.

Drug Interactions

Tegafur increases the effectiveness of other chemotherapeutic agents (oxaliplatin, raltitrexed, cyclophosphamide, methotrexate, doxorubicin, mitomycin) and radiation therapy (an increase in the risk of adverse events is possible).

The tolerability of tegafur improves with the simultaneous administration of calcium folinate.

When used concomitantly with phenytoin, it enhances the effect of the latter.

Inhibitors of microsomal oxidation in the liver increase the toxicity of tegafur.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 4 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.