THIOTEPA

Chemistry - An ethylene derivative alkylating agent antineoplastic, thiotepa occurs as fine, whitecrystalline flakes. The drug has a faint odor and is freely soluble in water or alcohol. Thiotepa mayalso be known as triethylenethiophosphoramide, TESPA, or TSPA.

Storage, Stability, Compatibility

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 opaqueis OK) or if a precipitate is present. If refrigerated, reconstituted solutions are stable for up to 5days.

Pharmacology - THIOTEPA

Thiotepa is an alkylating agent, thereby interfering with DNA replication and RNA transcription. It is cell-cycle non-specific. Thiotepa also has some immunosuppressive activity. When given via the intracavitary route, thiotepa is thought to control malignant effusions by adirect antineoplastic effect.
Uses, Indications - Veterinary indications for thiotepa include: systemic use for adjunctive therapyagainst carcinomas, intravesical administration for transitional cel tumors, and intracavitary use forneoplastic effusions.

Pharmacokinetics - THIOTEPA

Thiotepa is poorly absorbed from the GI tract. Systemic absorption is variable from the pleural cavity, bladder and after IM injection. Some studies in humans have shownthat absorption from bladder mucosa ranges from 10-100% of an administered dose. Distributioncharacteristics are not well described; it is unknown if the drug enters maternal milk. Thiotepa isextensively metabolized and then excreted in the urine.

Contraindications, Precautions, Reproductive Safety

Thiotepa is contraindicated in patientshypersensitive to it. The drug should be used cautiously (weigh risk versus benefit) in patients withhepatic dysfunction, bone marrow depression, infection, tumor cel infiltration of bone marrow, renal function impairment (adjust dosage) or have a history of urate urinary stones. Thiotepa has avery low therapeutic index and should only be used by clinicians with experience in the use ofcytotoxic agents and able to monitor therapy appropriately.
Thiotepa is potentially mutagenic and teratogenic and is not recommended for use during pregnancy. Although it is unknown whether thiotepa enters milk, use of milk replacer is recommendedfor nursing bitches or queens.

Adverse Effects, Warnings

When used systemically, leukopenia is the most likely adverse effectseen in small animals. Other hematopoietic toxicity (thrombocytopenia, anemia, pancytopenia) mayalso be noted. Intracavitary or intravesical instillation of thiotepa may also cause hematologictoxicity. GI toxicity (vomiting, diarrhea, stomatitis, intestinal ulceration) may be noted and humanpatients have reported dizziness and headache as well.
Overdosage, Acute Toxicity - There is no specific antidote for thiotepa overdose. Supportivetherapy, including transfusions of appropriate blood products may be beneficial for treatment ofhematologic toxicity.

Drug Interactions

Use extreme caution when used concurrently with other drugs that are alsomyelosuppressive, including many of the other antineoplastics and other bone marrow depressant drugs (e.g., chloramphenicol, flucytosine, amphotericin B, or colchicine). Bonemarrow depression may be additive. Use with other immunosuppressant drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) may increase the risk of infection. Live virus vaccines should be used with caution, if at all during therapy.
By activating plasminogen and increasing the amount of drug in tumor tissue, urokinase mayenhance the anti-tumor activity of thiotepa in the bladder.
Laboratory Considerations - Thiotepa may increase serum uric acid levels in some patients.