Thiotepa
Triethylenethiophosphoramide
Also known as: Thioplex · Ledertepa · Onco Tiotepa · Tespamin · NSC-6396 · thiophosphamide · triethylenethiophosphoramide · TSPA · WR-45312
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
This dose is based on body surface area (mg/m²). Convert body weight to body surface area before dosing.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Intracavitary use for neoplastic effusions or systemically for adjunctive therapy of carcinomas | 0.2-0.5 mg/m 2 | intracavitary; IV | Not specified | Not specified | 🌎 NA |
- Intracavitary use for neoplastic effusions or systemically for adjunctive therapy of carcinomas: Consultation with a veterinary oncologist and referral to current veterinary oncology references are strongly recommended.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Thiotepa is a highly potent, cell-cycle non-specific alkylating antineoplastic agent.
In veterinary medicine, it is primarily utilized for:
- Intracavitary instillation to manage malignant neoplastic effusions (e.g., pleural or peritoneal).
- Intravesical instillation for transitional cell carcinomas of the bladder (though studies indicate it is significantly less effective than systemic doxorubicin/cyclophosphamide protocols).
- Systemic adjunctive therapy for various carcinomas.
Clinical Pearl: Thiotepa has a very narrow therapeutic index. Because it is a hazardous cytotoxic drug, strict handling precautions (e.g., use of biologic safety cabinets, closed-system transfer devices, and appropriate PPE) are mandatory to protect veterinary personnel from mutagenic and teratogenic risks.
Mechanism of action
Thiotepa acts as a polyfunctional alkylating agent.
- Mechanism: It undergoes conversion to its active metabolite, TEPA, which directly cross-links DNA strands by binding to guanine bases.
- Pathway: DNA cross-linking → interference with DNA replication and RNA transcription → cell cycle arrest and apoptosis.
- Specificity: It is cell-cycle non-specific, meaning it exerts cytotoxic effects on both resting and actively dividing cells.
- When administered via the intracavitary route, it is believed to control malignant effusions through a direct, localized antineoplastic effect on the serosal surfaces.
Safety & warnings
Contraindications
- Hypersensitivity to thiotepa
- Pregnancy (teratogenic and mutagenic - FDA Category D)
Adverse effects
- Leukopenia (most common)
- Thrombocytopenia
- Anemia
- Pancytopenia
- Vomiting
- Diarrhea
- Stomatitis
- Intestinal ulceration
- Dizziness (reported in humans)
- Headache (reported in humans)
Precautions
WARNING: Thiotepa has a very low therapeutic index and should only be administered by clinicians experienced with cytotoxic agents.
- Organ Dysfunction: Use with extreme caution in patients with hepatic dysfunction or renal function impairment (dosage adjustment may be necessary).
- Bone Marrow: Weigh risks vs. benefits in patients with pre-existing bone marrow depression, active infections, or tumor cell infiltration of the bone marrow.
- Urolithiasis: Use cautiously in patients with a history of urate urinary stones, as thiotepa may increase serum uric acid levels.
- Nursing: It is unknown if thiotepa enters maternal milk; use of a milk replacer is strongly recommended for nursing bitches or queens.
Drug interactions
May increase the risk of severe infections due to additive immunosuppression.
Extreme caution required; bone marrow depression may be additive and lead to severe pancytopenia.
Increased risk of vaccine-induced infection or reduced vaccine efficacy; use with extreme caution, if at all.
Monitoring
- Clinical efficacy (tumor response or reduction in effusion)
- CBC with platelets (monitor closely for myelosuppression)
- Serum uric acid levels
Pharmacokinetics
Absorption
Poorly absorbed from the GI tract. Systemic absorption is variable from the pleural cavity, bladder, and after IM injection. Absorption from bladder mucosa ranges from 10-100% of an administered dose.
Distribution
Distribution characteristics are not well described; it is unknown if the drug enters maternal milk.
Metabolism
Extensively metabolized in the liver (primarily to its active metabolite, TEPA).
Elimination
Excreted primarily in the urine.
Overdose
There is no specific antidote for a thiotepa overdose.
Treatment is primarily supportive and symptomatic. If severe hematologic toxicity (profound myelosuppression) occurs, aggressive supportive therapy is required, which may include transfusions of appropriate blood products, broad-spectrum prophylactic antibiotics, and isolation to prevent secondary infections.
Available products
Formulations
- Lyophilized Powder for Injection: 15 mg, 30 mg
Human-labeled
- Thiotepa Lyophilized Powder for Injection: 15 mg & 30 mg in vials (Thioplex, generic)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store both the powder and the reconstituted solution refrigerated (2-8°C) and protected from light. Do not use solution that is grossly opaque (slightly opaque is OK) or if a precipitate is present. If refrigerated, reconstituted solutions are stable for up to 5 days.
Client information
Your pet has been prescribed a potent chemotherapy medication. Please read the following carefully:
- Toxicity Risks: This drug can cause severe side effects, including a drop in white blood cells (increasing infection risk), red blood cells (anemia), and platelets (bleeding risk). In rare cases, chemotherapy can cause secondary tumors or be life-threatening.
- When to Call the Vet: Contact your veterinarian immediately if your pet shows signs of abnormal bleeding, bruising, loss of appetite, vomiting, yellowing of the eyes/skin (jaundice), or signs of infection (like fever or extreme lethargy).
- Safe Handling at Home: Because this is a hazardous drug, your pet's bodily fluids (urine, feces, vomit) may contain traces of the medication for a few days after treatment. Wear disposable gloves when cleaning up waste, and wash your hands thoroughly afterward. Pregnant women, nursing mothers, and immunocompromised individuals should avoid contact with the pet's waste.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.