Oteracil potassium is not typically prescribed as a standalone drug but is a crucial component of the combination chemotherapy regimen known as Teysuno or S-1. This regimen also includes tegafur and gimeracil.
Usage
- Medical Conditions: Oteracil, as part of Teysuno (S-1), is primarily indicated for treating advanced gastric cancer (stomach cancer) in combination with cisplatin. It is also used in some regions for metastatic colorectal cancer, sometimes in combination with other chemotherapeutic agents like oxaliplatin or irinotecan, with or without bevacizumab.
- Pharmacological Classification: Antineoplastic antimetabolite; specifically, a fluoropyrimidine.
- Mechanism of Action (as part of Teysuno): Tegafur is a prodrug that is metabolized into 5-fluorouracil (5-FU), a cytotoxic agent. Gimeracil enhances 5-FU’s effects by inhibiting its degradation. Oteracil reduces gastrointestinal side effects associated with 5-FU by inhibiting orotate phosphoribosyltransferase (OPRT), an enzyme involved in 5-FU activation in the gut.
Alternate Names
- Oteracil potassium (especially in formulations)
- Part of Teysuno or S-1 (combined with tegafur and gimeracil)
- NSC-28841 (developmental code)
- 5-azaorotic acid
- Allantoxanic acid
- Oxonate
- Oxonic Acid
How It Works
- Pharmacodynamics: Oteracil, as part of Teysuno, primarily exerts its antineoplastic effect through the active metabolite of tegafur, 5-FU. 5-FU disrupts DNA and RNA synthesis, thereby inhibiting cell division and leading to cancer cell death.
- Pharmacokinetics: Tegafur is well-absorbed orally. All three drugs are metabolized in the liver. Oteracil inhibits the enzyme OPRT in the gastrointestinal tract, reducing the local activation of 5-FU and thereby decreasing gastrointestinal toxicity. Elimination occurs via renal/hepatic routes.
Dosage
Oteracil is administered as part of the Teysuno regimen, and its dosage information below pertains to its use within this combination.
Standard Dosage
Adults:
- Advanced Gastric Cancer: 25 mg/m² of tegafur (equivalent to approximately 37.5 mg/m² Teysuno containing 15 mg tegafur, 4.35 mg gimeracil, and 11.8 mg oteracil, or approximately 50 mg/m² Teysuno containing 20 mg tegafur, 5.8 mg gimeracil and 15.8 mg oteracil) twice daily (morning and evening) for 21 consecutive days, followed by a 7-day rest period. This 28-day cycle is repeated every four weeks, usually given in combination with cisplatin. Cisplatin is typically discontinued after six cycles, while Teysuno can be continued.
- Metastatic Colorectal Cancer: The dosage can vary depending on whether Teysuno is used alone or with other chemotherapy drugs. A common regimen is twice daily for 14 days followed by a 7-day rest, repeated every 3 weeks.
Children:
The safety and efficacy of Teysuno have not been established in children under 18 years, and its use is not recommended in this population.
Special Cases:
- Elderly Patients: No standard dose adjustment is generally recommended, though careful monitoring for side effects is crucial.
- Patients with Renal Impairment: For moderate impairment (CrCl 30-50 mL/min), the recommended dose is reduced to 20 mg/m² of tegafur twice daily. Teysuno is contraindicated in severe renal impairment (CrCl < 30 mL/min).
- Patients with Hepatic Dysfunction: While no formal dose adjustment is typically required, use with caution and careful monitoring are recommended, especially in severe hepatic impairment.
Clinical Use Cases
The dosage recommendations for clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are the same as the standard dosage guidelines adjusted for organ function as needed. There is no specific dosage change in these clinical settings for the indication of advanced gastric or metastatic colorectal cancer.
Dosage Adjustments
Dose modifications may be necessary based on individual patient tolerance and observed side effects, especially myelosuppression. Dosage should be reduced or temporarily withheld in cases of severe neutropenia, thrombocytopenia, or other significant adverse events.
Side Effects
Common Side Effects
- Nausea, vomiting
- Diarrhea
- Fatigue
- Anorexia (loss of appetite)
- Stomatitis (mouth sores)
- Hand-foot syndrome (palmar-plantar erythrodysaesthesia)
Rare but Serious Side Effects
- Severe myelosuppression (neutropenia, thrombocytopenia, anemia)
- Renal impairment (including acute renal failure)
- Liver dysfunction
- Cardiotoxicity (rare)
- Neurotoxicity (rare)
Long-Term Effects
Chronic side effects can include persistent fatigue, peripheral neuropathy, and secondary malignancies (rare).
Contraindications
- Hypersensitivity to tegafur, gimeracil, or oteracil
- History of severe reactions to fluoropyrimidine therapy
- Dihydropyrimidine dehydrogenase (DPD) deficiency
- Pregnancy and breastfeeding
- Severe bone marrow suppression
- Severe renal impairment (CrCl <30 mL/min)
- Concurrent use with other fluoropyrimidines
Drug Interactions
- CYP2A6 Inhibitors: Can decrease the efficacy of Teysuno.
- Anticoagulants (e.g., warfarin): Increased risk of bleeding.
- Other myelosuppressive drugs: Additive myelosuppression.
- Sorivudine and brivudine: Contraindicated due to severe drug interaction risk.
Pregnancy and Breastfeeding
Teysuno is contraindicated during pregnancy and breastfeeding due to the risk of fetal harm. Effective contraception is necessary during treatment and for a period after the last dose (duration varies by guidelines).
Drug Profile Summary
See above sections for usage, side effects, contraindications, drug interactions, and pregnancy/breastfeeding information. Dosage and monitoring parameters are also included above.
Popular Combinations
Teysuno is commonly used in combination with cisplatin for the first-line treatment of advanced gastric cancer. In colorectal cancer, it may be combined with oxaliplatin, irinotecan, and/or bevacizumab.
Precautions
- Patients should undergo DPD testing before starting treatment.
- Monitor for myelosuppression, renal function, and liver function during treatment.
- Patients should take precautions to avoid infections due to the risk of myelosuppression.
- Close monitoring of patients with renal or hepatic impairment is needed.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Oteracil in Teysuno?
A: Oteracil is dosed as part of Teysuno. See the detailed dosage information in the section above for specific dosage based on indication, body surface area, and organ function.
Q2: How does Oteracil contribute to the Teysuno regimen?
A: Oteracil minimizes gastrointestinal side effects by selectively inhibiting 5-FU activation in the gut.
Q3: Can Teysuno be used in patients with renal impairment?
A: Dosage adjustments are necessary for moderate renal impairment. It is contraindicated in severe renal impairment.
Q4: What are the most common side effects of Teysuno?
A: Nausea, vomiting, diarrhea, fatigue, anorexia, and myelosuppression are common side effects.
Q5: Are there any specific monitoring parameters during Teysuno treatment?
A: Yes, regular monitoring of blood counts (CBC), renal function tests (serum creatinine, CrCl), and liver function tests are essential during treatment.
Q6: Can Teysuno be used during pregnancy or breastfeeding?
A: No, Teysuno is contraindicated in pregnant and breastfeeding women due to the risk of fetal harm.
Q7: What is DPD deficiency, and why is it relevant to Teysuno treatment?
A: DPD is the primary enzyme involved in 5-FU metabolism. DPD deficiency can lead to severe toxicity from 5-FU. Patients should be tested for DPD deficiency before starting Teysuno.
Q8: What should I do if a patient experiences severe diarrhea while taking Teysuno?
A: Severe diarrhea can be a sign of toxicity. The drug should be temporarily discontinued, and supportive care should be provided. Dosage may need to be reduced upon re-challenge.
Q9: What are the drug interactions to be aware of with Teysuno?
A: Teysuno interacts with several medications, including other fluoropyrimidines, CYP2A6 inhibitors, some antiviral medications, and anticoagulants. A thorough medication reconciliation is important before starting Teysuno.
The information provided here is current as of February 16, 2025, and is intended for use by qualified medical professionals in India. Always consult the latest prescribing information and local guidelines for the most up-to-date information.
