Thiotepa

A to Z Drug Facts

Actions Thiotepa is a cell cycle nonspecific alkylating agent related to nitrogen mustard. Its radiomimetic action is believed to occur through the release of ethylenimine radicals, which disrupt the bonds of DNA. TEPA, which possesses cytotoxic activity, appears to be the major metabolite of thiotepa found in the serum and urine. The peak serum concentration of IV thiotepa 60 and 80 mg were 1331 and 1828 ng/mL, respectively. The elimination half-life of IV thiotepa 60 and 80 mg were 2.4 and 2.3 hr, respectively. The area under the curve (AUC) of IV thiotepa 60 and 80 mg were 2832 and 4127 ng/hr/mL, respectively. The total body clearance of IV thiotepa 60 and 80 mg were 446 and 419 mL/min, respectively.

 Indications Bladder cancer, palliative therapy of breast and ovarian carcinoma.

Prevention of pterygium recurrence after postoperative b-irradiation, autologous bone marrow transplantation.

 Contraindications History of hypersensitivity reaction, hepatic disease, renal disease, or bone marrow toxicity. Administer reduced doses if therapy is necessary in these patients.

 Route/Dosage

Breast and Ovarian Carcinoma

ADULTS: IV 0.3 to 0.4 mg/kg every 1 to 4 wk. Alternative regimens, 0.2 mg/kg/day for 4 to 5 days every 2 to 4 wk; or 6 mg/m²/day for 4 to 5 days every 2 to 4 wk.

Bladder Tumors

ADULTS: Intravesically 30 to 60 mg instilled (in 60 mL of sterile water) once weekly for 4 wk. Retain fluid in bladder for 2 hr. If patient can not retain for 2 hr, dilute successive doses in 30 mL of sterile water instead of 60 mL. It may be necessary to repeat course of therapy or give maintenance therapy with 30 to 60 mg intravesically once monthly for £ 1 yr. After local resection or fulguration of bladder tumors, prophylaxis with thiotepa 30 to 60 mg has been used.

Interactions

Pancuronium

Prolonged apnea and paralysis because of pancuronium occurred in a patient who received thiotepa.

Succinylcholine

Prolonged apnea because of succinylcholine occurred in a patient who had received thiotepa and other antineoplastics.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Confusion and somnolence at high doses used for bone marrow transplantation. With intrathecal use lower extremity weakness or pain, spinal cord demyelination, transient paresthesias. DERMATOLOGIC: Rash, hives, bronze hyperpigmentation after bone marrow transplantation. GI: Low potential for nausea and vomiting, anorexia, mucositis, intestinal ulceration, lower abdominal pain with intravesical use. GU: Chemical and hemorrhagic cystitis, hematuria with intravesical use, amenorrhea, interference with spermatogenesis. HEMATOLOGIC: Bone marrow suppression, leukocyte nadir at 10 to 30 days, bone marrow suppression from systemically absorbed thiotepa can occur after bladder instillation. SPECIALSENSES: Eye irritation and delayed periorbital skin depigmentation with ophthalmic use. OTHER: Acute leukemia and myelodysplastic syndrome with long-term intravesical use.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy have not been established. Fertility impairment: Thiotepa impaired fertility in male mice and inhibited implantation in female rats. Hematopoietic toxicity: This drug is highly toxic to the hematopoitic system. Perform weekly blood and platelet counts during therapy and for ³ 3 wk after therapy discontinuation. The most serious complication of excessive therapy is bone marrow depression, causing leukopenia, thrombocytopenia, and anemia. If WBC count falls to £ 3000/mm³, discontinue use. If the platelet count falls to 150,000/mm³, discontinue therapy. Mutagenesis: In vitro, it causes chromatid-type chromosomal aberations. Renal/Hepatic function impairment: If the benefits outweigh the potential risks, use in low doses and monitor hepatic and renal function.

 Administration/Storage

• Refrigerate powder for injection and protect from light.
• Reconstitute powder for injection by adding 1.5 mL sterile water for injection to each 15 mg vial to yield 10 mg/mL solution.
• Reconstituted solution is hypotonic and should be further diluted with 0.9% Sodium Chloride before administration. Do not use solutions which are opaque or contain precipitate.
• Reconstituted 10 mg/mL solution is stable for ³ 24 hr under refrigeration; however, thiotepa contains no preservative and the manufacturer recommends using the product within 8 hr.
• Diluted 5 mg/mL solutions prepared with 0.9% Sodium Chloride are stable for £ 24 hr at room temperature or under refrigeration. Diluted 0.5 mg/mL solutions must be used within 8 hr.
• IV, intravesical, or ophthalmic instillation.
• Prior to intravesical instillation, patients should not drink for 8 to 12 hr. While thiotepa is instilled, patient may be repositioned q 15 min to maximize area of contact.

 Assessment/Interventions

• Monitor CBC with differential at baseline, at least once weekly during therapy, and for ³ 3 wk after discontinuing therapy. Discontinue therapy for WBC < 3000/mm³ or platelet count < 150,000/mm³.

 Patient/Family Education

• Notify the health care provider in the case of any sign of bleeding (eg, epistaxis, easy bruising, change in color of urine, black stool) or infection (eg, fever, chills).
• Notify the health care provider if patient or partner may be pregnant. Use effective contraception during therapy.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts