TEPADINA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEPADINA (TEPADINA).

How it works

Alkylating agent that cross-links DNA, leading to inhibition of DNA replication and transcription, and cell death. Active against both dividing and non-dividing cells.

What the body does with it

Metabolism	Metabolized primarily by liver microsomal enzymes, including CYP3A4 and CYP2B6. Undergoes hydrolysis to monofunctional alkylating agents.
Excretion	Primarily renal: ~60-70% of the dose excreted unchanged in urine within 48 hours; biliary/fecal elimination accounts for <5%.
Half-life	Terminal elimination half-life: approximately 1.5-2.5 hours following IV administration; clinically, this short half-life supports myeloablative conditioning regimens with minimal accumulation.
Protein binding	Approximately 10-20% bound to plasma proteins (albumin and alpha1-acid glycoprotein).
Volume of Distribution	Vd: 30-60 L (0.4-0.8 L/kg); indicates extensive tissue distribution with penetration into cerebrospinal fluid and third-space fluids.
Bioavailability	IV: 100%; oral: not clinically used due to high first-pass metabolism (oral bioavailability <10%).
Onset of Action	IV: Onset of myelosuppression occurs within 24-48 hours; antineoplastic effect is seen within 1-3 days.
Duration of Action	Myelosuppression duration: Neutrophil nadir at days 7-14, recovery by days 21-28; immunosuppressive effects persist for 2-4 weeks.

Classification & Brands

Dosing & administration

IV: 1 mg/kg twice daily for 4 consecutive days (total dose 8 mg/kg) or 3.5 mg/m² once daily for 5 days (total dose 17.5 mg/m²) as part of conditioning regimen prior to hematopoietic progenitor cell transplantation.

Dosage form	POWDER
Renal impairment	GFR 10-50 mL/min: reduce dose by 25%; GFR <10 mL/min: reduce dose by 50% or consider alternative therapy.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or reduce dose by 80% with monitoring.
Pediatric use	1 mg/kg (or 33-50 mg/m² depending on protocol) IV over 2 hours daily for 3-5 days; weight-adjusted with BSA for children <10 kg.
Geriatric use	No specific dose adjustments; monitor for increased toxicity (renal, hepatic, bone marrow suppression). Consider starting at lower end of dosing range.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TEPADINA (TEPADINA).

Breastfeeding	Excreted in breast milk; M/P ratio 1.2. Discontinue breastfeeding due to potential severe infant toxicity (immunosuppression, neutropenia, carcinogenesis).
Teratogenic Risk	FDA Pregnancy Category D. First trimester: major congenital malformations (neural tube defects, cardiovascular anomalies) based on alkylating agent class effects; elective abortion risk. Second/third trimester: fetal growth restriction, bone marrow suppression, increased risk of preterm labor. All trimesters: possible fetal loss.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

WARNING: MYELOSUPPRESSION, SECONDARY MALIGNANCIES, AND HEPATOTOXICITY. Myelosuppression: Severe and potentially fatal myelosuppression occurs in all patients. Secondary Malignancies: Risk of secondary leukemia and other malignancies. Hepatotoxicity: Hepatic veno-occlusive disease (VOD) may be severe or fatal.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to thiotepa or any component of TEPADINA","Severe hepatic impairment (Child-Pugh class C)","Severe renal impairment (CrCl < 30 mL/min)"]

Clinical Precautions

Precautions

["Myelosuppression: Monitor complete blood counts frequently; severe neutropenia, thrombocytopenia, and anemia expected.","Hepatotoxicity: Monitor liver function tests; risk of VOD increased in patients with pre-existing liver disease.","Secondary malignancies: Long-term risk; monitor for new cancers.","Carcinogenicity: Known carcinogen.","Reproductive toxicity: Can cause fetal harm; advise effective contraception."]

Clinical Tips & Counseling

Drug interactions

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TEPADINA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEPADINA (TEPADINA).

How it works

Alkylating agent that cross-links DNA, leading to inhibition of DNA replication and transcription, and cell death. Active against both dividing and non-dividing cells.

What the body does with it

Metabolism	Metabolized primarily by liver microsomal enzymes, including CYP3A4 and CYP2B6. Undergoes hydrolysis to monofunctional alkylating agents.
Excretion	Primarily renal: ~60-70% of the dose excreted unchanged in urine within 48 hours; biliary/fecal elimination accounts for <5%.
Half-life	Terminal elimination half-life: approximately 1.5-2.5 hours following IV administration; clinically, this short half-life supports myeloablative conditioning regimens with minimal accumulation.
Protein binding	Approximately 10-20% bound to plasma proteins (albumin and alpha1-acid glycoprotein).
Volume of Distribution	Vd: 30-60 L (0.4-0.8 L/kg); indicates extensive tissue distribution with penetration into cerebrospinal fluid and third-space fluids.
Bioavailability	IV: 100%; oral: not clinically used due to high first-pass metabolism (oral bioavailability <10%).
Onset of Action	IV: Onset of myelosuppression occurs within 24-48 hours; antineoplastic effect is seen within 1-3 days.
Duration of Action	Myelosuppression duration: Neutrophil nadir at days 7-14, recovery by days 21-28; immunosuppressive effects persist for 2-4 weeks.

Classification & Brands

Dosing & administration

Dosage form	POWDER
Renal impairment	GFR 10-50 mL/min: reduce dose by 25%; GFR <10 mL/min: reduce dose by 50% or consider alternative therapy.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated or reduce dose by 80% with monitoring.
Pediatric use	1 mg/kg (or 33-50 mg/m² depending on protocol) IV over 2 hours daily for 3-5 days; weight-adjusted with BSA for children <10 kg.
Geriatric use	No specific dose adjustments; monitor for increased toxicity (renal, hepatic, bone marrow suppression). Consider starting at lower end of dosing range.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TEPADINA (TEPADINA).

Breastfeeding	Excreted in breast milk; M/P ratio 1.2. Discontinue breastfeeding due to potential severe infant toxicity (immunosuppression, neutropenia, carcinogenesis).
Teratogenic Risk	FDA Pregnancy Category D. First trimester: major congenital malformations (neural tube defects, cardiovascular anomalies) based on alkylating agent class effects; elective abortion risk. Second/third trimester: fetal growth restriction, bone marrow suppression, increased risk of preterm labor. All trimesters: possible fetal loss.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to thiotepa or any component of TEPADINA","Severe hepatic impairment (Child-Pugh class C)","Severe renal impairment (CrCl < 30 mL/min)"]