TEPADINA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TEPADINA (TEPADINA).
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.
| 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. |
| Molecular Weight | 189.26 |
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. |
| 1st trimester | Thiopeta is teratogenic in animal studies; human data limited. Avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | May cause fetal harm; use only if clearly needed. Consider fetal monitoring. |
| 3rd trimester | Avoid near term due to potential neonatal myelosuppression and immunosuppression. |
Clinical note
Comprehensive clinical and safety monograph for TEPADINA (TEPADINA).
| Placental transfer | Thiopeta crosses the placenta; animal studies confirm placental transfer. Human data limited but assumed. |
| Breastfeeding | Thiopeta is excreted into breast milk; potential for serious adverse effects in nursing infants. Discontinue breastfeeding during therapy and for at least 2 weeks after last dose. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to thiotepaSevere bone marrow suppressionActive infection
| 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. |
| Food/Dietary | No known specific food interactions. However, due to severe immunosuppression and risk of infection, avoid raw or undercooked meats, unpasteurized dairy, and unwashed fruits/vegetables to reduce risk of foodborne illness. |
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| L5 |
| 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 | Monitor complete blood counts, liver and renal function tests weekly. Fetal ultrasound for growth and anatomy. Amniocentesis for karyotype if high-dose. Serum drug levels not routinely recommended. |
| Fertility Effects | Causes premature ovarian failure and azoospermia. Reversible in some but permanent infertility is common. Alkylating agent class effect. |
| Clinical Pearls | TEPADINA (thiotepa) is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell transplantation. Monitor for myelosuppression, especially neutropenia and thrombocytopenia, with nadir at 6-10 days post-infusion. Administer antiemetic prophylaxis. Hydrate to minimize hemorrhagic cystitis risk; consider mesna if high cumulative doses. Teratogenic and carcinogenic; use effective contraception. Extravasation hazard; administer via central line. TEPADINA is dialyzable; consider alternative therapy in dialysis patients. Concomitant use of CYP3A4 inducers may reduce efficacy; CYP3A4 inhibitors may increase toxicity. |
| Patient Advice | This drug can severely lower blood cell counts, increasing infection and bleeding risk; report fever, bruising, or unusual bleeding immediately. · You may experience nausea and vomiting; take anti-nausea medications as prescribed. · Drink plenty of fluids (at least 2-3 liters daily) to protect your bladder. · Avoid conception during treatment and for at least 12 months after; use effective barrier contraception. · Do not receive live vaccines during or shortly after treatment. · Inform your doctor if you are breastfeeding or plan to breastfeed; this drug passes into breast milk and may harm the infant. · TEPADINA may cause infertility; discuss fertility preservation options before starting treatment. |