thiotepa (Rx)

Frequency Not Defined

Asthenia

Fatigue

Seizures

Fever

Nausea

Vomiting

Loss of appetite

Stomatitis

Diarrhea

Myelosuppression

Leukemia

Immune hypersensitivity reaction

Oligozoospermia

Amenorrhea

Alopecia (slow)

Hyperpigmentation

Rash

Injection site pain

Contraindications

Hypersensitivity

Hepatic, renal, bone marrow damage (maybe used in low dose if benefit>risk)

Cautions

Avoid pregnancy

May be mutagenic and teratogenic

Myelosuppression may occur

Secondary malignancies may develop (potentially carcinogenic)

Caution in hepatic impairment (may require dose reduction; use may also be contraindicated depending on type of hepatic impairment)

Caution in renal impairment (may require dose reduction; use may also be contraindicated depending on type of hepatic impairment)

Use appropriate precautions for handling and disposal

Pregnancy Category: D

Lactation: not known if excreted in breast milk, do not nurse

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Alkylating agent that produces crosslinking of DNA strands by reacting with phosphate groups to inhibit protein synthesis, DNA, and RNA

Pharmacokinetics

Half-life elimination: 2.4 hour (parent drug), 17.6 hr (metabolite)

Metabolism: Liver

Total body clearance: 446-419 mL/min

Excretion: Urine

Dialyzable: Yes

IV Incompatibilities

Additive: cisplatin

Y-site: cisplatin, filgrastim, minocycline, vinorelbine

IV Compatibilities

Solution: D5W(?), NS(?)

Y-site (partial list): acyclovir, allopurinol, ampicillin/sulbactam, bleomycin, carboplatin, clindamycin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dopamine, etoposide, etoposide phosphate, filgrastim, fluconazole, fluorouracil, gemcitabine, heparin, idarubicin, lorazepam, MgSO4, metronidazole, mitomycin, morphine, ondansetron, KCl, prochlorperazine, teniposide, tobramycin, vancomycin, vinblastine, vincristine

IV Preparation

Reconstitute in 1.5 mL SWI to 10 mg/mL which is stable for 8 hr at refrigeration; further dilution in NS, D5W, or LR should be used immediately (within 1 hr of preparation)

Standard IV dilution

• IVP: use 10 mg/mL solution
• IVPB: dose/250 mL D5W; further dilution in NS, D5W, or LR should be used immediately (within 1 hr of preparation)
• Continuous 24 hr IV infusion Dose >250 mg: QS to 50 mL (total volume) in NSDose 230-250 mg: QS to 45 mL (total volume) in NSDose 200-230 mg: QS to 40 mL (total volume) in NS

IV Administration

Administer over 1 min

Solutions should be filtered through a 0.22 micron filter prior to administration

1 mg/mL solution is considered isotonic

Storage

Store intact vials under refrigeration (2-8°C)

Protect from light