DESCRIPTION
MECHANISM OF ACTION
The generation of this combo was conceived under the reported activation by the transformation of tegafur to 5-fluorouracil. These findings have convened with results that suggested that the degradation
of 5-fluorouracil can be depressed by the addition of uracil.1 Uracil competitively inhibits the catabolic action of dihydropyrimidine dehydrogenase. This combined activity allows a significant increase in blood and tissue 5-fluorouracil levels by inhibiting its first-pass hepatic metabolism.2,9 The active metabolites of tegafur inhibit the enzyme thymidylate synthase (5-fluoro-deoxyuridine-monophosphate) and intercalate into RNA (5-fluorouridine-triphosphate).9
its first-pass hepatic metabolism.2,9 The active metabolites of tegafur inhibit the enzyme thymidylate synthase (5-fluoro-deoxyuridine-monophosphate) and intercalate into RNA (5-fluorouridine-triphosphate).9
Distribution
The volume of distribution of tegafur is reported to be 59 L while the uracil volume of distribution of 474 L.
ABSORPTION
The absorption into systemic circulation is very rapid and the peak concentration is reached within 1-2 hours.
After a single dose of tegafur/uracil of 300 mg/m2/day in three divided doses, tegafur plasma concentration of >1000 ng/ml are maintained
throughout the 8-hour dosing interval, whereas uracil concentrations decline rapidly following the peak concentration. The plasma concentration of 5-fluorouracil peaks at 30-60 min after administration with 200 ng/ml and remain detectable for 8-hour dosing interval.
There is no significant long-term accumulation of either uracil, tegafur or 5-fluorouracil.8
INDICATIONS.
1.Tegafur and uracil combination drugs are used to treat metastatic colorectal cancer, a condition in which the cancer cells have moved to other body parts in adult patients.
2.Tegafur and uracil is a fixed-dose combination (1:4) used as a first-line treatment in combination with calcium folinate.
3.Colorectal cancer affects nearly 1 million people each year across the globe and is estimated to be more common in developed countries than in developing countries.
DOSAGE RANGE
1.The doses of tegafur and uracil are calculated based on the body surface area taking into account the individual patient’s height and weight and given
repeatedly for 35 days (1 treatment cycle).
2.The recommended daily dose of tegafur is 300 mg/m2 and uracil is 672 mg/m2 along with oral calcium folinate as 90mg (30 mg/dose) given
three times daily (every 8 hours) for 28 days continuously followed by a 7-day treatment-free period.
3. If the dose amount of tegafur and uracil combination cannot be divided equally the highest dose can be taken in the morning
followed by a low dose in the afternoon and the evening.
4. The doses of tegafur and uracil can be reduced if any blood-related or other types of toxicities occur during the treatment.
Drug Interactions
The doctor should be informed before prescribing tegafur-uracil and calcium folinate if the patient is taking any prescription, Over-The-Counter drugs, or any herbal supplements or has a plan to take them,
to prevent unwanted side effects caused by the medications when taken with tegafur-uracil and calcium folinate.
In case of severe side effects, the dose of tegafur-uracil can be reduced.
SPECIAL CONSIDERATIONS
• Liver function should be evaluated during the treatment with tegafur-uracil and calcium folinate. The patient should be monitored for the levels of
liver enzymes and promptly treated for the symptoms and signs of liver dysfunction along with dose reduction.
• Patients should be monitored for diarrhea during tegafur-uracil therapy and must be treated with fluid and electrolytes to prevent severe dehydration.
• Women of reproductive potential should be tested for their pregnancy status before initiating the treatment. Tegafur-uracil therapy should be
started only if the results are negative as it can harm the baby in the womb.
• Tegafur-uracil can affect the fertility status and patients who wish to have a baby in the future must be advised to use the
facilities of a sperm or egg bank.
• Women should not breastfeed during the treatment with tegafur-uracil and even for a few months after stopping the treatment.
• Patients should use effective contraceptive measures to avoid pregnancy. In case pregnancy is confirmed during the treatment
patients must consult their doctor immediately.
• Tegafur-uracil can reduce the count of white blood cells putting patients at a risk of developing an infection. Monitor the patients for any symptoms and signs of infection.
• Platelet transfusion is recommended for some patients who have low platelet count due to the treatment with tegafur-uracil. Patients should be advised to consult the doctor
if any unusual bleeding occurs.
TOXICITY
Acute toxicity from the combination use of tegafur was associated with nausea, vomiting, diarrhoea, mucositis, gastrointestinal irritation,
bleeding, bone marrow depression, and respiratory failure 5. Overdose may lead to fatal complications.
SPECIFICATION
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