thiotepa
Thioplex

Available forms
Available by prescription only
Injection: 15-mg vials

Indications and dosages
 Dosages and indications may vary. Check current literature for recommended protocol.
 Breast and ovarian cancer, Hodgkin’s disease, lymphomas. Adults and adolescents age 12 and older: 0.2 mg/kg I.V. daily for 4 to 5 days, repeated q 2 to 4 weeks. Or, 0.3 to 0.4 mg/kg I.V. q 1 to 4 weeks.
 Bladder tumor. Adults and adolescents age 12 and older: 30 to 60 mg in 30 to 60 ml of normal saline solution (thiotepa in distilled water) instilled in bladder once weekly for 4 weeks. Patient should retain the solution for 2 hours. If patient can’t retain it, give 30 ml.
 Neoplastic effusions. Adults and adolescents age 12 and older: 0.6 to 0.8 mg/kg intracavity or intratumor q 1 to 4 weeks.
 Malignant meningeal neoplasm ◇. Adults: 1 to 10 mg/m² intrathecally, once to twice weekly.

Pharmacodynamics
Antineoplastic action: Thiotepa exerts its cytotoxic activity as an alkylating agent, cross-linking strands of DNA and RNA and inhibiting protein synthesis, resulting in cell death.

Pharmacokinetics
Absorption: Incompletely absorbed across the GI tract; absorption from the bladder is variable, ranging from 10% to 100% of an instilled dose. Absorption is increased by certain pathologic conditions. I.M. and pleural membrane absorption of thiotepa is also variable.
Distribution: Distributed readily into CNS after I.V. administration.
Metabolism: Metabolized extensively in the liver.
Excretion: Drug and its metabolites are excreted in urine. Half-life is 2 1/2 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with severe bone marrow, hepatic, or renal dysfunction. Use cautiously in patients with impaired renal or hepatic function or bone marrow suppression.

Interactions
Drug-drug. Alkylating agents, irradiation therapy: Causes toxicity. Avoid use together.
Anticoagulants, aspirin: Increases risk of bleeding. Avoid use together.
Myelosuppressive drugs: Causes additive myelosuppression. Monitor patient closely.
Neuromuscular blockers: Prolongs muscular paralysis. Monitor patient closely.
Succinylcholine: Prolongs respirations and apnea. Monitor patient closely. Avoid use together.

Adverse reactions
CNS: fever, headache, dizziness, fatigue, weakness.
EENT: laryngeal edema, blurred vision, conjunctivitis.
GI: nausea, vomiting, abdominal pain, anorexia, stomatitis.
GU: amenorrhea, decreased spermatogenesis, dysuria, urine retention, hemorrhagic cystitis.
Hematologic: leukopenia (begins within 5 to 10 days), thrombocytopenia, neutropenia, anemia.
Respiratory: asthma.
Skin: pain at injection site, alopecia, hives, rash, dermatitis.
Other: hypersensitivity, anaphylaxis.

Effects on lab test results
• May increase uric acid levels. May decrease pseudocholinesterase levels.
• May decrease hemoglobin and lymphocyte, platelet, WBC, RBC, and neutrophil counts.

Overdose and treatment
Signs and symptoms of overdose are mainly extensions of adverse reactions, particularly leukopenia and thrombocytopenia, effects that may lead to infection or bleeding. Dosages within or slightly above the recommended therapeutic dosages have been linked to dose-related, life-threatening hematopoietic toxicity.
 There’s no known antidote for thiotepa overdose; whole blood or platelet transfusions have been beneficial. Thiotepa is removed by dialysis.

Special considerations
• Use only sterile water for injection to reconstitute. Refrigerated solution is stable for 8 hours.
• Drug can be given by all parenteral routes, including direct injection into the tumor.
• Drug may be mixed with procaine 2% or epinephrine 1:1,000, or both, for local use.
• Drug may be further diluted to larger volumes with normal saline solution, D₅W, or lactated Ringer’s solution for I.V. infusion, intracavitary injection, or perfusion therapy.
• Filter solutions through a 0.22-micron filter before administration. Don’t use solutions that are opaque or precipitate after filtration.
• Monitor uric acid. To prevent hyperuricemia with resulting uric acid nephropathy, allopurinol may be given; keep patient well hydrated.
• Avoid all I.M. injections when platelet count is less than 100,000/mm³.
• Toxicity may be delayed and prolonged because drug binds to tissues and stays in body several hours.
• Stop drug or decrease dose if WBC count decreases to less than 4,000/mm³ or if platelet count decreases to less than 150,000/mm³.
• Monitor CBC weekly for at least 3 weeks after last dose.
• Refrigerate dry powder; protect from light.
Pregnant patients
• Drug shouldn’t be used during pregnancy.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. However, because of risk of serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.
Pediatric patients
• Safety and efficacy haven’t been established.

Patient education
• Encourage patient to maintain an adequate fluid intake to facilitate the excretion of uric acid.
• Instruct patient to avoid OTC products containing aspirin.
• Tell patient to avoid people with infections.
• Advise patient that hair should grow back.
• Warn patient to report even mild infections, sore throat, fever, or unusual bruising or bleeding.
• Instruct patient to use effective contraception measures. Tell woman to immediately report if she becomes pregnant.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use