Tegonat 15 — Tegafur, Gimeracil & Oteracil Capsules, 42 Caps · Tegafur / Gimeracil / Oteracil

Tegonat 15 is supplied as hard gelatin capsules.

Qualitative and Quantitative Composition per Capsule:

• Active Ingredients:
  • — Tegafur — 15 mg.
  • — Gimeracil — 4.35 mg.
  • — Oteracil potassium — 11.8 mg.
• Excipients: Lactose monohydrate, magnesium stearate, talc, capsule shell components (gelatin, titanium dioxide, colorants).

Packaging and Presentation: Hard gelatin capsules containing powder or granules. 7 capsules per blister strip. 6 blister strips (total 42 capsules) are packaged in an outer carton displaying Tegonat 15 (Tegafur, Gimeracil and Oteracil Capsules) along with Natco Pharma corporate graphics and official prescribing information.

Pharmacodynamics:
Tegonat combines three active agents in a fixed ratio. Tegafur is converted into 5-fluorouracil (5-FU), inhibiting DNA synthesis and cell division via thymidylate synthase blockade. Gimeracil prevents hepatic DPD degradation of 5-FU, maintaining therapeutic exposure. Oteracil potassium reduces GI phosphorylation of 5-FU, lessening gastrointestinal toxicity without impairing antitumor efficacy.

Pharmacokinetics:

• Absorption: All three components are rapidly and almost completely absorbed from the GI tract. Peak plasma concentration ($C_{max}$) is reached within 1–2 hours.
• Distribution: Plasma protein binding of tegafur is minimal (~4–7%); gimeracil and oteracil binding is similarly low. Volume of distribution is adequate for tissue penetration.
• Metabolism: Tegafur is metabolized in the liver to 5-FU primarily via CYP2A6 cytochrome P450 isoenzymes. Gimeracil and oteracil are excreted mostly unchanged.
• Elimination: Excreted predominantly renally via urine. Terminal elimination half-life ($T_{1/2}$) of tegafur is approximately 7–10 hours.

Tegonat 15 is indicated in adult patients for:

• Gastric Cancer: Treatment of unresectable or recurrent/metastatic gastric cancer (as monotherapy or combination regimens).
• Colorectal Cancer: Adjuvant treatment of colon cancer following radical surgery, as well as metastatic colorectal cancer.
• Head and Neck Cancer: Treatment of squamous cell carcinoma of the head and neck.
• Breast and Non-Small Cell Lung Cancer: Utilized per oncology protocols in combination regimens.

Tegonat 15 is administered orally twice daily (morning and evening), approximately 30 minutes after a meal.

Dosing Regimen:
Dosage is calculated individually by the attending oncologist based on the patient's body surface area (BSA). The 15 mg strength (in combination with 20 mg capsules) allows precise formulation of the exact prescribed dose:

• BSA < 1.25 m²: 40 mg (tegafur equivalent) twice daily.
• BSA 1.25 to < 1.5 m²: 50 mg twice daily.
• BSA ≥ 1.5 m²: 60 mg twice daily.

Standard Schedule: Administered daily for 28 consecutive days followed by a 14-day rest period (42-day cycle). This cycle is repeated as prescribed.

Administration of Tegonat 15 is contraindicated in:

• Hypersensitivity: Known hypersensitivity to tegafur, gimeracil, oteracil potassium, or any excipient.
• Severe Bone Marrow Suppression: Severe leukopenia, neutropenia, or thrombocytopenia.
• Severe Renal Impairment: Creatinine clearance < 30 ml/min.
• Severe Hepatic Impairment: Pronounced hepatic dysfunction.
• Concurrent Medications: Co-administration with other fluoropyrimidines or sorivudine/brivudine (severe life-threatening drug interaction).
• Pregnancy and Lactation: Contraindicated in pregnant or breastfeeding women.

Evaluated drug interactions include:

• Other Fluoropyrimidines (capecitabine, 5-fluorouracil): Strict contraindication due to severely amplified toxicity.
• Antiviral Agents (sorivudine, brivudine): Inhibit DPD enzymes, leading to massive accumulation of 5-FU and potentially fatal toxicity. Tegonat must not be initiated within 4 weeks of sorivudine or brivudine cessation.
• Phenytoin: Tegafur may increase plasma phenytoin concentrations, elevating toxicity risks. Monitoring is required.

Pregnancy:
Tegonat 15 is contraindicated during pregnancy due to teratogenic and embryo-fetal toxicity risks. Women of childbearing potential must use effective contraception during treatment and post-therapy.

Lactation:
Excretion into breast milk is unstudied. Breastfeeding must be discontinued during treatment.

The most frequent and clinically significant adverse reactions include:

• Gastrointestinal Tract: Stomatitis, diarrhea, nausea, vomiting, anorexia, abdominal pain (GI toxicity is mitigated by oteracil but remains notable).
• Hematologic Toxicity: Leukopenia, neutropenia, anemia, thrombocytopenia. Regular complete blood counts are mandatory.
• Hepatic & Renal Parameters: Elevations in transaminases (ALT, AST), bilirubin, and serum creatinine.
• Skin & Appendages: Skin hyperpigmentation, alopecia, hand-foot syndrome (palmar-plantar erythrodysesthesia).
• General Disorders: Fatigue, asthenia, pyrexia.

Symptoms:
Overdose manifests as exaggerated adverse reactions: severe myelosuppression (profound leukopenia, thrombocytopenia), severe stomatitis, diarrhea, nausea, vomiting, and mucosal ulceration.

Treatment:
No specific antidote exists. Supportive and symptomatic care should be initiated, including hospitalization, hematologic monitoring, blood component transfusions, and colony-stimulating factors if indicated.

Storage Requirements for Tegonat 15:

• 🌡️ Temperature Range: Store in a dry, light-protected place at temperatures not exceeding 25–30 °C.
• 💧 Moisture Protection: Keep in original blister packaging to protect capsules from moisture.
• 👶 Safety Precautions: Keep strictly out of reach of children.
• ⏳ Shelf Life: Stated on carton and blisters. Do not use past expiration date. Prescription-only hospital medicine.

To verify authenticity of genuine Tegonat 15 manufactured by Natco Pharma, inspect the following features:

• ✅ Corporate Logo: Distinctive blue-green Natco Pharma corporate logo printed on the outer carton and blister foil.
• ✅ Packaging Markings: Clear factory printing displaying Batch No., Mfg. Date, Exp. Date, and product designation Tegonat 15 (Tegafur, Gimeracil and Oteracil Capsules).
• ✅ Blister Quantity: Standard box contains exactly 6 blister strips of 7 capsules each (total 42 capsules).
• ✅ Print Quality: High-grade packaging artwork without color fading or typography errors.