Trabec — Trabectedin for Injection 1 mg, 1 Vial Cold chain · Storage +2…+8 °C

Trabec 1 mg is supplied in the form of a lyophilized powder for concentrate for solution for infusion.

Qualitative and Quantitative Composition per Vial:

• • Active Ingredient: Trabectedin — 1 mg.
• • Excipients: Sucrose, potassium dihydrogen phosphate, phosphoric acid, potassium hydroxide (for pH adjustment).

Packaging and Presentation: White to off-white lyophilized cake or powder. Supplied in a single-use clear glass vial containing 1 mg trabectedin, sealed with a rubber stopper and aluminum flip-off cap. Each vial is packaged in an outer carton displaying Trabec (Trabectedin for Injection) 1 mg alongside official Natco Pharma corporate graphics.

Pharmacodynamics:
Trabectedin binds to the minor groove of DNA, altering helix conformation and inhibiting transcription of key oncogenic drivers. It disrupts the transcription-coupled nucleotide excision repair (TC-NER) system, generating double-strand DNA breaks and inducing G2/M phase arrest and apoptosis. Trabectedin also reduces the production of pro-angiogenic factors and inflammatory cytokines by tumor-associated macrophages.

Pharmacokinetics:

• • Distribution: Features a large volume of distribution and high plasma protein binding (approximately 97%).
• • Metabolism: Extensively metabolized in the liver, predominantly via the cytochrome P450 enzyme CYP3A4.
• • Elimination: Terminal elimination half-life is prolonged (approximately 180 hours). Excreted primarily in feces (~58%) and minimally in urine (~6%).

Trabec 1 mg is indicated in adult patients for:

• • Advanced Soft Tissue Sarcoma: Treatment of patients with advanced soft tissue sarcoma (specifically liposarcoma and leiomyosarcoma) after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents.
• • Relapsed Ovarian Cancer: Treatment of relapsed platinum-sensitive ovarian cancer in combination with pegylated liposomal doxorubicin (PLD).

Trabec 1 mg is intended strictly for intravenous administration under oncologist supervision.

Reconstitution and Dilution Instructions:

• • Reconstitution: Reconstitute the 1 mg vial by injecting 20 ml of Sterile Water for Injection (resulting in 0.05 mg/ml concentration).
• • Dilution: Immediately dilute the reconstituted solution in 500 ml of 0.9% Sodium Chloride or 5% Dextrose injection solution.

Dosing Regimen:

• • Soft Tissue Sarcoma: The recommended dose is 1.5 mg/m2 body surface area, administered as a 24-hour continuous intravenous infusion every 3 weeks.
• • Premedication: Premedication with intravenous corticosteroids (e.g., 20 mg dexamethasone IV) 30 minutes prior to infusion is mandatory for hepatoprotection and antiemetic prophylaxis.

Administration of Trabec 1 mg is contraindicated in:

• • Hypersensitivity: Known hypersensitivity to trabectedin or any excipient.
• • Infections: Concurrent severe or uncontrolled active infections.
• • Severe Hepatic Impairment: Bilirubin elevations or severe hepatic dysfunction.
• • Myelosuppression: Baseline absolute neutrophil count < 1,500/µl or platelet count < 100,000/µl prior to treatment cycle.
• • Pregnancy and Lactation: Contraindicated in pregnant or nursing women.

Evaluated drug interactions for Trabec include:

• • CYP3A4 Inhibitors: Potent CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, grapefruit juice) increase trabectedin systemic exposure and risk of toxicity.
• • CYP3A4 Inducers: Potent CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St. John's wort) lower trabectedin exposure, compromising therapeutic efficacy.
• • Hepatotoxic and Myelotoxic Agents: Co-administration increases risk of liver damage and severe bone marrow suppression.
• • Vaccines: Live attenuated vaccines must be avoided during therapy.

Pregnancy:
Trabec 1 mg is strictly contraindicated during pregnancy due to genotoxic and teratogenic effects. Male and female patients must use effective contraception during therapy and for 3 months (women) and 5 months (men) after the last dose.

Lactation:
Breastfeeding is strictly contraindicated during treatment and for 3 months following the final dose.

The most frequent adverse events associated with trabectedin include:

• • Hematologic Toxicity (Very Common): Neutropenia, thrombocytopenia, anemia, leukopenia. Febrile neutropenia may occur.
• • Hepatobiliary Disorders (Very Common): Transient elevations in serum transaminases (ALT, AST), alkaline phosphatase, and bilirubin.
• • Gastrointestinal Tract: Nausea, vomiting, anorexia, constipation, diarrhea, stomatitis, abdominal pain.
• • Nervous System & General: Fatigue, asthenia, headache, peripheral edema.
• • Musculoskeletal System: Myalgia, arthralgia, potential risk of rhabdomyolysis (monitored via CPK levels).

Symptoms:
Overdose results in severe myelosuppression (deep neutropenia, thrombocytopenia), severe hepatotoxicity, multi-organ failure, and gastrointestinal toxicity.

Treatment:
No specific antidote exists. Supportive care including blood product transfusions, granulocyte colony-stimulating factors (G-CSF), hepatoprotective support, and vital sign monitoring must be initiated.

Storage Requirements for Trabec 1 mg:

• ❄️ Cold Storage: Store refrigerated between 2 °C and 8 °C (36 °F–46 °F). Do not freeze.
• ☀️ Light Protection: Keep vial in the outer carton to protect from light.
• 💧 Reconstituted Solution: Infusion solutions should be administered immediately after preparation.
• 👶 Safety Precautions: Keep out of reach of children.
• ⏳ Shelf Life: Stated on vial label and box. Do not use past expiration date. Prescription-only medicine for hospital use.

To verify the authenticity of original Trabec 1 mg produced by Natco Pharma, check the following details:

• ✅ Natco Logo: Official blue-green Natco Pharma logo on the outer box and vial label.
• ✅ Packaging Details: Clear factory printing displaying Batch No., Mfg. Date, Exp. Date, and product name Trabec (Trabectedin for Injection) 1 mg.
• ✅ Vial Cap Seal: Intact plastic flip-off seal over aluminum crimp ring.
• ✅ Box Integrity: High-quality cardboard, clear typography without blur, containing an undamaged lyophilized cake vial.