TEPADINA AND SODIUM CHLORIDE
Clinical safety rating
safeNo significant drug interactions Can cause hypernatremia and fluid overload.
TepadinA (thiotepa) is an alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription, leading to cell death. It is cell cycle phase-nonspecific.
| Metabolism | Primarily metabolized by cytochrome P450 enzymes, including CYP2B6 and CYP3A4, via oxidative desulfuration to active metabolites (e.g., tepa). Also undergoes glutathione conjugation. |
| Excretion | Primarily renal; approximately 60-70% of the dose is excreted unchanged in urine within 24 hours; minor fecal elimination (<10%) |
| Half-life | Terminal elimination half-life: 1.5–3.5 hours; clinically, the short half-life allows high-intensity dosing with stem cell support |
| Protein binding | Minimal (<10%); primarily albumin |
| Volume of Distribution | 0.3–0.5 L/kg; indicates limited extravascular distribution |
| Bioavailability | Oral: approximately 75% (variable, 30-100%); intravenous: 100% |
| Onset of Action | Intravenous: within 2 hours; oral: 2-4 hours |
| Duration of Action | Myelosuppression lasts 14–28 days; antineoplastic effect persists for weeks; requires stem cell rescue |
| Molecular Weight | Thiotepa: 189.2 Da; Sodium chloride: 58.44 Da |
6.25 mg/m2 (based on ideal body weight) intravenously over 2 hours every 6 hours for 16 doses (total dose 100 mg/m2) as part of conditioning regimen prior to hematopoietic stem cell transplantation.
| Dosage form | POWDER |
| Renal impairment | No specific dose adjustments are provided for renal impairment. Use with caution in patients with renal impairment due to potential for nephrotoxicity from the drug or its metabolites; monitor renal function closely. |
| Liver impairment | No specific dose adjustments are provided for hepatic impairment based on Child-Pugh score. Use with caution in patients with hepatic impairment; monitor liver function tests closely. |
| Pediatric use | Children and adolescents: Same dose as adults (6.25 mg/m2 intravenously over 2 hours every 6 hours for 16 doses), based on ideal body weight. Safety and efficacy in neonates and infants have not been established. |
| Geriatric use | No specific dose adjustments recommended for elderly patients. Use with caution due to higher likelihood of decreased renal and hepatic function, and monitor for increased toxicity. |
| 1st trimester | Contraindicated due to teratogenicity; avoid pregnancy. |
| 2nd trimester | Contraindicated due to teratogenicity; avoid pregnancy. |
| 3rd trimester | Contraindicated due to teratogenicity; avoid pregnancy. |
Clinical note
No significant drug interactions Can cause hypernatremia and fluid overload.
| FDA category | Animal |
| Placental transfer | Thiotepa and its metabolites cross the placenta extensively, achieving fetal concentrations similar to maternal. |
| Breastfeeding | Contraindicated; thiotepa is excreted in breast milk and may cause severe adverse effects in nursing infants. |
| Lactation Rating | L5 |
| Teratogenic Risk | TEPADINA is a known teratogen in animals and is presumed to cause fetal harm when administered to pregnant women. Based on its mechanism of action as an alkylating agent, there is a high risk of teratogenicity, including congenital malformations and fetal demise, particularly during the first trimester. In the second and third trimesters, exposure may lead to fetal growth restriction, myelosuppression, or long-term developmental effects. |
| Fetal Monitoring | Complete blood count (CBC) with differential should be monitored frequently during therapy due to myelosuppression. Hepatic and renal function tests should be assessed prior to and during treatment. For pregnant patients, fetal monitoring may include ultrasound for growth and anatomy, as well as nonstress testing or biophysical profile as clinically indicated. Neonates should be monitored for myelosuppression and infection. |
| Fertility Effects | TEPADINA can cause gonadal suppression and infertility in both males and females. In males, it may cause azoospermia or oligospermia. In females, it may cause ovarian failure, premature menopause, or irreversible infertility. Effects are dose- and duration-dependent. |
■ FDA Black Box Warning
WARNING: THIOTEPA IS HIGHLY TOXIC TO BONE MARROW. SEVERE MYELOSUPPRESSION, INCLUDING DEATH, MAY OCCUR. THIOTEPA IS CARCINOGENIC AND MUTAGENIC. IT SHOULD BE ADMINISTERED ONLY BY PHYSICIANS EXPERIENCED IN CANCER CHEMOTHERAPY.
| Common Effects | fluid replacement |
| Serious Effects |
Hypersensitivity to thiotepaPregnancyBreastfeedingSevere bone marrow suppression
| Precautions | Bone marrow suppression: Monitor blood counts frequently; dose adjustments may be necessary., Carcinogenicity: Long-term use increases risk of secondary malignancies (e.g., myelodysplastic syndrome, acute leukemia)., Mutagenicity: Can cause chromosomal damage; use contraception during therapy., Renal and hepatic impairment: Dose adjustment may be needed., Hemorrhagic cystitis: Adequate hydration and frequent voiding recommended; monitor for hematuria., Embryo-fetal toxicity: Can cause fetal harm; avoid pregnancy. |
| Food/Dietary | No specific food interactions. Maintain adequate hydration. Avoid grapefruit juice due to potential CYP3A4 interaction. Advise small, frequent meals to manage nausea. |
| Clinical Pearls | TEPADINA AND SODIUM CHLORIDE is used as a conditioning agent prior to hematopoietic stem cell transplantation (HSCT). Administer via intravenous infusion over 1-2 hours. Monitor for infusion reactions (bronchospasm, urticaria) and have resuscitation equipment available. Pre-medicate with anticonvulsants (e.g., phenytoin) to prevent seizure due to CNS toxicity. Observe for hepatotoxicity, especially veno-occlusive disease (VOD), and consider defibrotide prophylaxis. Adjust dose for renal impairment (CrCl < 60 mL/min). Use with caution in patients with pre-existing hepatic dysfunction. |
| Patient Advice | This medication is used to prepare your body for a stem cell transplant. · You will receive this drug intravenously (through a vein) in the hospital. · Common side effects include nausea, vomiting, diarrhea, and mouth sores. · You may experience temporary hair loss and skin rash. · Report any signs of infection (fever, chills), bleeding, or unusual bruising immediately. · Avoid driving or operating machinery if you feel dizzy or sleepy. · Do not receive live vaccines during treatment. · Use effective contraception during and for at least 6 months after treatment. · Drink plenty of fluids unless advised otherwise. · Inform your doctor if you have liver or kidney disease. |
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