Thiotepa Lyophilized Powder for Injection: 15 mg & 30 mg in vials

By | April 21, 2016

Thiotepa

ANTINEOPLASTIC

Highlights of Prescribing Information

  • Antineoplastic used systemically for carcinomas, intracavitary for neoplastic effusions, & intravesical for transitional carcinomas; rarely used in small animal oncology
  • Contraindications: Hypersensitivity to thiotepa; Caution: Hepatic dysfunction, bone marrow depression, infection, tumor cell infiltration of bone marrow, renal dysfunction, or history of urate urinary stones
  • Adverse Effects: Leukopenia most likely adverse effect; other hematopoietic toxicity (thrombocytopenia, anemia, pancytopenia), GI toxicity possible. Intracavitary or intravesical instillation can also cause hematologic toxicity.
  • Potentially teratogenic; use milk replacer if patient nursing
  • Monitor diligently

What Is Drug Used For?

Veterinary indications for thiotepa include: systemic use for adjunctive therapy against carcinomas, and intracavitary use for neoplastic effusions. In dogs with transitional cell bladder carcinoma, intravesical instillation of thiotepa had significantly less efficacy (mean survival time = 57 days) when compared to a systemic doxorubicin/ cyclophosphamide protocol (mean survival time = 259 days).

Pharmacology / Actions

Thiotepa is an alkylating agent, thereby interfering with DNA replication and RNA transcription. It is cell cycle non-specific. Thiotepa has some immunosuppressive activity. When given via the intracavitary route, thiotepa is thought to control malignant effusions by a direct antineoplastic effect.

Pharmacokinetics

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 shown that absorption from bladder mucosa ranges from 10-100% of an administered dose. Distribution characteristics are not well described; it is unknown if the drug enters maternal milk. Thiotepa is extensively metabolized and then excreted in the urine.

Before you take Drug

Contraindications / Precautions / Warnings

Thiotepa is contraindicated in patients hypersensitive to it. The drug should be used cautiously (weigh risk versus benefit) in patients with hepatic dysfunction, bone marrow depression, infection, tumor cell infiltration of bone marrow, renal function impairment (adjust dosage) or with a history of urate urinary stones. Thiotepa has a very low therapeutic index and should only be used by clinicians with experience in the use of cytotoxic agents and able to monitor therapy appropriately.

Adverse Effects

When used systemically, leukopenia is the most likely adverse effect seen in small animals. Other hematopoietic toxicity (thrombocytopenia, anemia, pancytopenia) may be noted. Intracavitary or intravesical instillation of thiotepa may cause hematologic toxicity. GI toxicity (vomiting, diarrhea, stomatitis, intestinal ulceration) may be noted and human patients have reported dizziness and headache as well.

Reproductive / Nursing Safety

Thiotepa is potentially mutagenic and teratogenic and is not recommended for use during pregnancy. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks.)

Although it is unknown whether thiotepa enters milk, use of milk replacer is recommended for nursing bitches or queens.

Overdosage / Acute Toxicity

There is no specific antidote for thiotepa overdose. Supportive therapy, including transfusions of appropriate blood products, may be beneficial for treatment of hematologic toxicity.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving thiotepa and may be of significance in veterinary patients:

■ IMMUNOSUPPRESSIVE DRUGS (e.g., azathioprine, cyclophosphamide, corticosteroids): Use with other immunosuppressant drugs may increase the risk of infection

■ MYELOSUPPRESSIVE DRUGS (e.g., chloramphenicol, flucytosine, ampho-tericin B, or colchicine): Use extreme caution when used concurrently with other drugs that are also myelosuppressive, including many of the other antineoplastics and other bone marrow depressant drugs; bone marrow depression maybe additive

■ VACCINES, LIVE: Live virus vaccines should be used with caution during therapy, if at all

Laboratory Considerations

■ Thiotepa may increase serum uric acid levels in some patients

How to use Drug

Drug dosage for dogs:

a) For intracavitary use neoplastic effusions or systemically for adjunctive therapy of carcinomas: 0.2 – 0.5 mg/m2 intracavitary; IV. ()

Monitoring

■ Efficacy

■ CBC with platelets

Client Information

■ Clients must be briefed on the possibilities of severe toxicity developing from this drug, including drug-related neoplasms or mortality

■ Clients should contact veterinarian should the animal exhibit clinical signs of abnormal bleeding, bruising, anorexia, vomiting, jaundice, or infection

Chemistry / Synonyms

An ethylene derivative alkylating agent antineoplastic, thiotepa occurs as fine, white crystalline flakes. The drug has a faint odor and is freely soluble in water or alcohol.

Thiotepa may also be known as: NSC-6396, TESPA, thiophosphamide, triethylenethiophosphoramide, TSPA, WR-45312, Ledertepa, Onco Tiotepa, Tespamin, or Thioplex.

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.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Thiotepa Lyophilized Powder for Injection: 15 mg & 30 mg in vials; Thioplex (Amgen); generic, (Sicor); (Rx)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008