Thioplan 100 — Thiotepa for Injection 100 mg, 1 Vial Cold chain · Storage +2…+8 °C

Thioplan 100 is supplied in the form of a lyophilized powder for solution for injection.

Qualitative and Quantitative Composition per Vial:

• Active Ingredient: Thiotepa — 100 mg.
• Excipients: Sodium chloride, sodium hydroxide and/or hydrochloric acid (for pH adjustment).

Packaging and Presentation: White lyophilized powder or cake. Supplied in a single-use clear glass vial containing 100 mg thiotepa, sealed with a rubber stopper and an aluminum crimp cap with a flip-off plastic lid. Each vial is packaged in an outer carton displaying Thioplan (Thiotepa Injection IP) 100 mg alongside official Natco Pharma corporate graphics.

Pharmacodynamics:
Thiotepa is a polyfunctional alkylating agent. Its cytotoxic mechanism involves alkylation of DNA nucleophilic sites, resulting in cross-linking between DNA strands, inhibition of nucleic acid synthesis, and blockade of tumor cell division. It exhibits pronounced myelosuppressive and antitumor activity.

Pharmacokinetics:

• Absorption and Distribution: Rapidly distributes into body tissues and fluids following intravenous administration. Penetrates the blood-brain barrier into cerebrospinal fluid and serous cavities. Plasma protein binding is minimal (~10–30%).
• Metabolism: Metabolized in the liver (primarily via cytochrome P450 enzymes) into an active metabolite, tepa.
• Elimination: The terminal elimination half-life of thiotepa ranges from 1.5 to 2 hours. Excreted primarily via the kidneys (~85% as metabolites and unchanged drug within 24 hours).

Thioplan 100 is indicated in adult and pediatric patients as part of mono- or combination chemotherapy for:

• High-Dose Chemotherapy (Conditioning Regimens): Preparation for bone marrow or hematopoietic stem cell transplantation in hematological malignancies, lymphomas, and solid tumors.
• Breast and Ovarian Malignancies: Advanced forms of breast and ovarian cancer.
• Superficial Bladder Cancer: Intravesical administration for prophylaxis of recurrence following transurethral resection.
• Central Nervous System Tumors: Meningeal leukemia or brain tumors (via intrathecal or systemic administration).
• Malignant Effusions: Intracavitary administration for malignant ascites or pleural effusion.

Thioplan 100 is administered parenterally (intravenously, including high-dose protocols, intravesically, intracavitary, or intrathecally) depending on clinical indications and treatment protocols.

Reconstitution Instructions:
Reconstitute the 100 mg vial with Sterile Water for Injection (typically 10 ml, yielding a 10 mg/ml concentration). The resulting concentrated solution may be further diluted in larger volumes of compatible infusion solutions (e.g., 0.9% Sodium Chloride).

Dosing Regimen:
Dose is individualized by a medical oncologist based on the chemotherapy protocol (standard vs. high-dose conditioning), patient body weight or surface area, bone marrow reserve, and concomitant therapies.

Administration of Thioplan 100 is contraindicated in:

• Hypersensitivity: Known hypersensitivity to thiotepa or any excipient.
• Severe Bone Marrow Suppression: Baseline leukopenia (< 3,000/µl) or thrombocytopenia (< 100,000/µl), except in specialized conditioning regimens prior to stem cell transplantation.
• Active Infections: Severe acute active infections.
• Pregnancy and Lactation: Contraindicated in pregnant or nursing women.
• Vaccination: Concurrent administration with live vaccines.

Evaluated drug interactions for Thioplan include:

• Myelosuppressive Agents: Co-administration with other chemotherapy drugs or radiation therapy significantly increases bone marrow toxicity.
• CYP450 Inhibitors: Drugs affecting hepatic enzyme activity may alter thiotepa metabolism.
• Succinylcholine: Thiotepa suppresses serum pseudocholinesterase activity, potentially prolonging succinylcholine-induced neuromuscular blockade.

Pregnancy:
Thioplan 100 is contraindicated during pregnancy due to teratogenic, mutagenic, and embryotoxic effects. Patients of reproductive age must utilize reliable contraception during therapy and for several months post-treatment.

Lactation:
Breastfeeding must be discontinued during thiotepa therapy.

The most frequent and serious adverse reactions associated with thiotepa include:

• Hematologic Toxicity (Very Common): Leukopenia, neutropenia, thrombocytopenia, anemia, increasing risks of severe infection and hemorrhage.
• Gastrointestinal Tract: Nausea, vomiting, anorexia, severe mucositis (stomatitis), diarrhea, abdominal pain.
• Urinary System: Dysuria, hemorrhagic cystitis (especially with intravesical instillation or high doses).
• Local Reactions: Pain and inflammation at the infusion site.
• Other: Skin rash, alopecia, amenorrhea, azoospermia, transient liver enzyme elevations.

Symptoms:
Overdose manifests as profound bone marrow suppression (leading to severe aplasia), severe mucositis, serious infectious complications, and bleeding disorders.

Treatment:
No specific antidote exists. Supportive and symptomatic care should be provided: blood product transfusions, broad-spectrum antibiotics, granulocyte colony-stimulating factors (G-CSF), and intensive patient monitoring in an intensive care setting.

Storage Requirements for Thioplan 100:

• ❄️ Cold Storage: Store lyophilized powder in a refrigerator at 2 °C to 8 °C (36 °F–46 °F). Do not freeze.
• ☀️ Light Protection: Keep vial in the outer carton to protect from light.
• 💧 Reconstituted Solution: Reconstituted solutions should be used immediately; limited refrigerated storage may be permissible in strict accordance with institutional clinical protocols.
• 👶 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 Thioplan 100 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 Thioplan (Thiotepa Injection IP) 100 mg.
• ✅ Vial Cap Seal: Intact plastic flip-off seal over aluminum crimp ring.
• ✅ Box Integrity: High-quality cardboard artwork with crisp typography and a securely sealed vial.