THIOTEPA
Clinical safety rating: avoid
Contraindicated (not allowed)
Alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription.
| Metabolism | Primarily metabolized by CYP2B6 and CYP3A4 to active metabolite TEPA; also undergoes spontaneous degradation. |
| Excretion | Primarily renal; 60-70% excreted unchanged in urine within 24-72 hours. Minor biliary/fecal elimination accounts for <10%. |
| Half-life | Terminal elimination half-life is approximately 1.5-4.5 hours. Clinically, due to rapid clearance, dosing intervals are typically every 1-4 weeks. |
| Protein binding | Approximately 10-20% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5-1.0 L/kg (range 0.6-1.6 L/kg). This indicates extensive distribution into total body water and some tissue binding, but not extensive sequestration. |
| Bioavailability | Oral bioavailability is low (<10%) due to poor absorption and first-pass metabolism. Intravesical: systemic absorption is minimal (<1% of dose). |
| Onset of Action | Intravesical: time to antitumor effect is within days to weeks for superficial bladder cancer. Intravenous: clinical effects may be observed within 1-3 weeks after administration. |
| Duration of Action | Duration of antineoplastic effect is variable, but myelosuppression typically persists for 2-3 weeks, with recovery usually within 4-6 weeks. Nadir for leukocytes and platelets occurs around 2 weeks after administration. |
| Molecular Weight | 189.22 |
0.3-0.4 mg/kg intravenously every 1-4 weeks; or 0.5-1 mg/kg intravenously every 2-4 weeks (commonly 60 mg/m² IV every 1-4 weeks).
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: administer 75% of normal dose; CrCl <10 mL/min: administer 50% of normal dose. Consider dose reduction or alternative in severe impairment. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated or reduce dose by 75% with caution. |
| Pediatric use | Children: 1.5-3 mg/kg intravenously every 4 weeks; or 0.5-1 mg/kg intrathecally (for meningeal neoplasia). |
| Geriatric use | Start at lower end of dosing range (e.g., 0.3 mg/kg IV) with careful monitoring for myelosuppression. No specific dose adjustment based solely on age. |
| 1st trimester | Thiotepa is embryotoxic and teratogenic in animal studies; avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | Use only if clearly needed; potential fetal harm based on animal data and limited human data. |
| 3rd trimester | Avoid near term due to risk of neonatal myelosuppression and other adverse effects. |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression.
| Placental transfer | Thiotepa crosses the placenta; detectable levels in fetal tissues. |
| Breastfeeding | Thiotepa is excreted in human milk; due to potential for serious adverse reactions in nursing infants, discontinue breastfeeding or discontinue drug. |
| Lactation Rating |
■ FDA Black Box Warning
Thiotepa is a highly toxic alkylating agent with a significant risk of severe myelosuppression (leukopenia, thrombocytopenia, anemia). Fatal neutropenia and thrombocytopenia have occurred. Monitor blood counts frequently. Thiotepa also has carcinogenic, mutagenic, and teratogenic potential. Handle with extreme caution.
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to thiotepaSevere bone marrow depressionPregnancy (especially first trimester)
| Precautions | Myelosuppression (dose-limiting), hepatotoxicity, neurotoxicity (confusion, dizziness, headache), reproductive toxicity, secondary malignancies, extravasation injury. |
| Food/Dietary | No clinically significant food interactions have been reported. Avoid grapefruit juice as a precaution due to potential CYP3A4 inhibition, though evidence is limited. Maintain adequate hydration to prevent drug-induced cystitis. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | Thiotepa is embryotoxic and teratogenic in animal studies. Human data are limited, but based on its mechanism as an alkylating agent, there is a high risk of fetal malformations, particularly during the first trimester. Use is contraindicated in pregnancy, especially in the first trimester, due to potential for severe fetal harm including congenital anomalies, intrauterine growth restriction, and fetal death. Second and third trimester exposure may also cause fetal harm, including myelosuppression and increased risk of neonatal infections. |
| Fetal Monitoring | Complete blood counts (CBC) with differential and platelets should be obtained weekly during therapy. Monitor for signs of myelosuppression, infection, bleeding, and hepatotoxicity. In pregnant patients, fetal monitoring with ultrasound for growth and anatomy is recommended. Newborns exposed in utero should be monitored for myelosuppression and long-term effects. |
| Fertility Effects | Thiotepa is an alkylating agent and is associated with gonadal suppression and infertility in both males and females. It may cause permanent amenorrhea and azoospermia. Fertility preservation options should be discussed prior to therapy. |
| Clinical Pearls | Thiotepa is an alkylating agent used in high-dose chemotherapy regimens, particularly for hematopoietic stem cell transplantation conditioning. Avoid concurrent use with live vaccines. Monitor for myelosuppression, especially thrombocytopenia and neutropenia. Infusion reactions may occur and require premedication with antihistamines and corticosteroids. Extravasation risk is low but may cause tissue irritation. Thiotepa crosses the blood-brain barrier; CNS toxicity is dose-limiting. Administer with antiemetic prophylaxis. Renal function monitoring is essential as thiotepa is renally eliminated. |
| Patient Advice | This medication may lower your blood cell counts, increasing risk of infection, bleeding, and fatigue. Report fever, bruising, or unusual bleeding immediately. · Avoid becoming pregnant or fathering a child during treatment; use effective contraception. Thiotepa can harm a fetus. · You may experience nausea, vomiting, or diarrhea; take antiemetics as prescribed and stay hydrated. · Avoid live vaccines (e.g., MMR, varicella, nasal flu) during treatment and for 6 months after. · Report any new confusion, headache, seizures, or vision changes as thiotepa can affect the central nervous system. · Rarely, allergic reactions may occur; seek help if you have hives, difficulty breathing, or swelling of the face/throat. |