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thiotepa; thiophosphamide (Tespa, Thioplex)

Tradenames: Tespa, Thioplex. Indications: - adenocarcinoma of the breast & ovary - breast cancer, ovarian cancer - chronic lymphocytic leukemia - Hodgkin's lymphoma - non-Hodkin's lymphoma - malignant effusions - ascites - carcinoma of the bladder Contraindications: 1) severe myelosuppression 2) pre-exsisting hepatic, renal or bone marrow damage Dosage: 1) IV: 12-16 mg/m2 every 1-4 weeks 2) intravesicular: 30-60 mg every 4 weeks 3) intrathecal: 1-10 mg/m2 once to twice weekly Powder for injection: 15 mg. (1 mg/mL is isotonic) Pharmacokinetics: 1) extensively metabolized by the liver 2) 1/2life 2-3 hours from plasma 3) 1/2life 6-9 hours from CSF after intrathecal administration Adverse effects: 1) common (> 10%) a) myelosuppression - dose-limting toxicity - severe thrombocytopenia (cumulative & dose-related) - moderate to severe leukopenia - pancytopenia may be fatal - onset 7-10 days - nadir 14 days - recovery 28 days b) pain at site of injection 2) less common (1-10%) - hyperuricemia, dizziness, fever, headache, alopecia, rash, pruritus, stomatitis, hematuria, nausea/vomiting* 3) uncommon (< 1%) - alopecia, rash, dizziness, fever, tightness of the throat, anorexia, allergic reactions, hemorrhagic cystitis 4) other - mild nausea* (emetic potential is low) - phlebitis - dysuria - cystitis (rare) - cognitive impairment (cumulative dose-related) - secondary carcinogenesis Drug interactions: 1) succinylcholine: increased apnea with concurrent administration 2) other alkylating agents & radiation therapy intensifies toxicity rather than enhances therapeutic benefits Test interactions: increases serum K+ Mechanism of action: 1) alkylating agent 2) interferes with DNA base-pairing

Interactions

drug adverse effects of alkylating agents

General

alkylating agent

Properties

MISC-INFO: elimination route LIVER 1/2life 2-3 HOURS pregnancy-category D

Database Correlations

PUBCHEM cid=5453

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Deprecated Reference