THIOPLEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for THIOPLEX (THIOPLEX).

How it works

Thiotepa is an alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription. It is a prodrug that undergoes metabolic activation to form aziridine radicals.

What the body does with it

Metabolism	Thiotepa is extensively metabolized in the liver primarily by cytochrome P450 enzymes (CYP3A4 and CYP2B6) to active and inactive metabolites. The major active metabolite is TEPA (triethylenephosphoramide).
Excretion	Primarily renal; approximately 30-50% of the dose excreted unchanged in urine within 24 hours. Biliary/fecal elimination accounts for <10%.
Half-life	Terminal elimination half-life 2-4 hours (adults with normal renal function); prolonged in renal impairment (up to 10 hours).
Protein binding	Approximately 10-20% (primarily albumin; minimal binding due to rapid hydrolysis).
Volume of Distribution	0.5-1.0 L/kg (indicating limited tissue distribution; primarily remains in extracellular fluid).
Bioavailability	IV: 100%; intravesical: negligible systemic absorption (<1% with intact bladder mucosa).
Onset of Action	IV: immediate (within minutes); intracavitary: 5-10 minutes; intravesical: 30-60 minutes.
Duration of Action	IV: 2-6 hours (myelosuppression may persist for 7-14 days, nadir at 5-7 days). Intravesical: 30-60 minutes with dwell time.

Classification & Brands

Dosing & administration

IV dose of 4 mg/kg at 7-day intervals or 2 mg/kg at 2-week intervals, administered as a slow IV infusion over 5-10 minutes.

Dosage form	INJECTABLE
Renal impairment	For GFR 10-50 mL/min: administer 50% of normal dose; for GFR <10 mL/min: administer 25% of normal dose.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 33%; Child-Pugh C: reduce dose by 50%.
Pediatric use	IV dose of 0.5-1 mg/kg every 7-14 days, not to exceed adult dose; adjust for renal and hepatic function.
Geriatric use	Start at lower end of dosing range (e.g., 2 mg/kg IV every 2 weeks) and titrate based on response and tolerance; monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for THIOPLEX (THIOPLEX).

Breastfeeding	Thiopental is excreted into breast milk in low levels. Milk-to-plasma ratio is approximately 0.8 to 0.9. Limited data suggest minimal risk to full-term infants at usual doses. Caution in preterm or ill infants. Monitor infant for sedation and feeding difficulties.
Teratogenic Risk	Pregnancy Category D. Thiopental is known to cross the placenta. First trimester: potential teratogenicity based on animal studies; avoid unless necessary. Second and third trimesters: associated with neonatal respiratory depression, hypotonia, and drowsiness; use only for essential indications. Prolonged exposure may cause withdrawal symptoms in neonates.

Warnings & precautions

■ FDA Black Box Warning

Thiotepa is a highly toxic drug with significant myelosuppression. Administer only under supervision of a physician experienced in cancer chemotherapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to thiotepa","Severe myelosuppression (e.g., absolute neutrophil count <1500/μL, platelets <100,000/μL)","Pregnancy (category D; teratogenic)"]

Clinical Precautions

Precautions

["Myelosuppression (dose-limiting toxicity; monitor blood counts)","Carcinogenicity (secondary malignancies reported)","Hypersensitivity reactions (including anaphylaxis)","Renal toxicity (monitor renal function)","Pulmonary toxicity (interstitial pneumonitis reported)","Hepatotoxicity","Neurotoxicity (with intrathecal administration)"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

THIOPLEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for THIOPLEX (THIOPLEX).

How it works

Thiotepa is an alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription. It is a prodrug that undergoes metabolic activation to form aziridine radicals.

What the body does with it

Metabolism	Thiotepa is extensively metabolized in the liver primarily by cytochrome P450 enzymes (CYP3A4 and CYP2B6) to active and inactive metabolites. The major active metabolite is TEPA (triethylenephosphoramide).
Excretion	Primarily renal; approximately 30-50% of the dose excreted unchanged in urine within 24 hours. Biliary/fecal elimination accounts for <10%.
Half-life	Terminal elimination half-life 2-4 hours (adults with normal renal function); prolonged in renal impairment (up to 10 hours).
Protein binding	Approximately 10-20% (primarily albumin; minimal binding due to rapid hydrolysis).
Volume of Distribution	0.5-1.0 L/kg (indicating limited tissue distribution; primarily remains in extracellular fluid).
Bioavailability	IV: 100%; intravesical: negligible systemic absorption (<1% with intact bladder mucosa).
Onset of Action	IV: immediate (within minutes); intracavitary: 5-10 minutes; intravesical: 30-60 minutes.
Duration of Action	IV: 2-6 hours (myelosuppression may persist for 7-14 days, nadir at 5-7 days). Intravesical: 30-60 minutes with dwell time.

Classification & Brands

Dosing & administration

IV dose of 4 mg/kg at 7-day intervals or 2 mg/kg at 2-week intervals, administered as a slow IV infusion over 5-10 minutes.

Dosage form	INJECTABLE
Renal impairment	For GFR 10-50 mL/min: administer 50% of normal dose; for GFR <10 mL/min: administer 25% of normal dose.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 33%; Child-Pugh C: reduce dose by 50%.
Pediatric use	IV dose of 0.5-1 mg/kg every 7-14 days, not to exceed adult dose; adjust for renal and hepatic function.
Geriatric use	Start at lower end of dosing range (e.g., 2 mg/kg IV every 2 weeks) and titrate based on response and tolerance; monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for THIOPLEX (THIOPLEX).

Breastfeeding	Thiopental is excreted into breast milk in low levels. Milk-to-plasma ratio is approximately 0.8 to 0.9. Limited data suggest minimal risk to full-term infants at usual doses. Caution in preterm or ill infants. Monitor infant for sedation and feeding difficulties.
Teratogenic Risk	Pregnancy Category D. Thiopental is known to cross the placenta. First trimester: potential teratogenicity based on animal studies; avoid unless necessary. Second and third trimesters: associated with neonatal respiratory depression, hypotonia, and drowsiness; use only for essential indications. Prolonged exposure may cause withdrawal symptoms in neonates.

Warnings & precautions

■ FDA Black Box Warning

Thiotepa is a highly toxic drug with significant myelosuppression. Administer only under supervision of a physician experienced in cancer chemotherapy.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to thiotepa","Severe myelosuppression (e.g., absolute neutrophil count <1500/μL, platelets <100,000/μL)","Pregnancy (category D; teratogenic)"]