Alkylating cytotoxic Pregnancy: Contraindicated during pregnancy and breast-feeding. Women of childbearing potential must use effective contraception during treatment and have a pregnancy test before treatment is started. In pre-clinical studies thiotepa caused embryofoetal lethality and teratogenicity. Thiotepa may impair male and female fertility; male patients should seek sperm cryopreservation before therapy and should not father a child while treated or during the year after cessation of treatment (§4.6).

Thiotepa (Specialist drug)

Brand names: Tepadina

Thiotepa is an alkylating cytotoxic agent used in conditioning regimens before haematopoietic stem cell transplantation and in certain solid tumours and bladder cancer. It is a specialist drug given under specialist supervision.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Conditioning before haematopoietic progenitor cell transplantation (HPCT), in combination with other chemotherapy — dose depends on the type of HPCT and the disease. Adults, AUTOLOGOUS HPCT, haematological diseases: 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) as a single daily infusion for 2 up to 4 consecutive days before autologous HPCT, depending on the combination with other chemotherapeutic medicinal products.

Route: Intravenous infusion over 2-4 hours via a central venous catheter. Reconstitute each vial with 10 mL sterile water for injection, then dilute the total volume in 500 mL of sodium chloride 9 mg/mL (0.9%) solution for injection (1000 mL if the dose is higher than 500 mg).

Frequency: Single daily infusion (or divided into two daily infusions for some regimens) for 1 up to 5 consecutive days before HPCT, depending on the regimen.

Max: Total maximum cumulative dose over the entire conditioning treatment, by indication — Adult autologous: haematological diseases and lymphoma 900 mg/m2 (24.32 mg/kg); CNS lymphoma 370 mg/m2 (10 mg/kg); multiple myeloma 750 mg/m2 (20.27 mg/kg); solid tumours 800 mg/m2 (21.62 mg/kg); breast cancer 800 mg/m2 (21.62 mg/kg); CNS tumours 750 mg/m2 (20.27 mg/kg); ovarian cancer 500 mg/m2 (13.51 mg/kg); germ cell tumours 750 mg/m2 (20.27 mg/kg). Adult allogeneic: haematological diseases and leukaemia 555 mg/m2 (15 mg/kg); lymphoma 370 mg/m2 (10 mg/kg); multiple myeloma 185 mg/m2 (5 mg/kg); thalassaemia 370 mg/m2 (10 mg/kg).

ADULT AUTOLOGOUS HPCT — Lymphoma: 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) single daily infusion, 2 up to 4 consecutive days. CNS lymphoma: 185 mg/m2/day (5 mg/kg/day) single daily infusion for 2 consecutive days. Multiple myeloma: 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) single daily infusion for 3 consecutive days. Solid tumours: 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) divided in one or two daily infusions, 2 up to 5 consecutive days. Breast cancer: 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) single daily infusion, 3 up to 5 consecutive days. CNS tumours: 125 mg/m2/day (3.38 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) divided in one or two daily infusions, 3 up to 4 consecutive days. Ovarian cancer: 250 mg/m2/day (6.76 mg/kg/day) single daily infusion on 2 consecutive days. Germ cell tumours: 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) single daily infusion for 3 consecutive days. ADULT ALLOGENEIC HPCT — Haematological diseases: 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided in one or two daily infusions, 1 up to 3 consecutive days. Lymphoma: 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions. Multiple myeloma: 185 mg/m2/day (5 mg/kg/day) single daily infusion. Leukaemia: 185 mg/m2/day (5 mg/kg/day) to 481 mg/m2/day (13 mg/kg/day) divided in one or two daily infusions, 1 up to 2 consecutive days. Thalassaemia: 370 mg/m2/day (10 mg/kg/day) divided in two daily infusions. PAEDIATRIC POPULATION (per the SPC; doses are body-surface-area based with mg/kg equivalents, and are indication-specific — not reduced to a single per-kg dose here) — Autologous HPCT, solid tumours: 150 mg/m2/day (6 mg/kg/day) to 350 mg/m2/day (14 mg/kg/day) single daily infusion, 2 up to 3 consecutive days, maximum cumulative 1050 mg/m2 (42 mg/kg). Autologous HPCT, CNS tumours: 250 mg/m2/day (10 mg/kg/day) to 350 mg/m2/day (14 mg/kg/day) single daily infusion for 3 consecutive days, maximum cumulative 1050 mg/m2 (42 mg/kg). Allogeneic HPCT, haematological diseases: 125 mg/m2/day (5 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) divided in one or two daily infusions, 1 up to 3 consecutive days, maximum cumulative 375 mg/m2 (15 mg/kg). Allogeneic HPCT, leukaemia: 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, maximum cumulative 250 mg/m2 (10 mg/kg). Allogeneic HPCT, thalassaemia: 200 mg/m2/day (8 mg/kg/day) to 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, maximum cumulative 250 mg/m2 (10 mg/kg). Allogeneic HPCT, refractory cytopenia: 125 mg/m2/day (5 mg/kg/day) single daily infusion for 3 consecutive days, maximum cumulative 375 mg/m2 (15 mg/kg). Allogeneic HPCT, genetic diseases: 125 mg/m2/day (5 mg/kg/day) single daily infusion for 2 consecutive days, maximum cumulative 250 mg/m2 (10 mg/kg). Allogeneic HPCT, sickle cell anaemia: 250 mg/m2/day (10 mg/kg/day) divided in two daily infusions, maximum cumulative 250 mg/m2 (10 mg/kg). In children, if the dose is lower than 250 mg, an appropriate volume of sodium chloride 0.9% may be used to obtain a final concentration between 0.5 and 1 mg/mL. Hepatic impairment: not studied; caution needed, especially in severe impairment; no dose modification for transient alterations of hepatic parameters. Elderly: no dose adjustment deemed necessary. Thiotepa must not be administered concurrently with cyclophosphamide when both are in the same conditioning regimen — deliver thiotepa after completion of any cyclophosphamide infusion. Administration must be supervised by a physician experienced in conditioning treatment prior to HPCT. Handle with gloves; wash skin thoroughly with soap and water and flush mucous membranes with water after accidental contact.

Dose adjustments

Renal

Studies in renally impaired patients have not been conducted. As thiotepa and its metabolites are poorly excreted in the urine, dose modification is not recommended in patients with mild or moderate renal insufficiency; however, caution is recommended (§4.2).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients (§4.3)
Pregnancy and lactation (§4.3, §4.6)
Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines (§4.3)

Side effects

Infections / increased infection susceptibility (very common)
Cytopenias — leukopenia, thrombocytopenia, febrile neutropenia, anaemia (very common)
Acute and chronic graft-versus-host disease (very common)
Gastrointestinal disorders and mucosal inflammation (very common)
Haemorrhagic cystitis (very common)
Leukoencephalopathy (reported, sometimes fatal, in patients with multiple previous chemotherapies including methotrexate and radiotherapy)

Interactions

Live attenuated vaccines (except yellow fever vaccine, which is contraindicated), phenytoin and fosphenytoin — concomitant use is not recommended (§4.4, cross-referencing §4.5)
Cyclophosphamide — must not be administered concurrently; thiotepa must be delivered after completion of any cyclophosphamide infusion (§4.4)
Inhibitors of CYP2B6 or CYP3A4 — patients should be carefully monitored clinically during concomitant use (§4.4)
Other cytotoxic agents (e.g. busulfan, fludarabine, cyclophosphamide) — thiotepa may induce pulmonary toxicity additive to their effects (§4.4)

Clinical monograph

How it works

It is a polyfunctional alkylating agent that cross-links DNA, disrupting replication and causing cytotoxicity in dividing cells.

Prescribing in practice

It causes profound myelosuppression, which is the intended effect in transplant conditioning but mandates intensive haematological support and infection precautions.
It is excreted in part through the skin and can cause skin reactions; frequent washing and dressing changes are advised to reduce local toxicity during high-dose use.
It is mutagenic, carcinogenic and teratogenic; effective contraception is required and handling must follow cytotoxic precautions.

Monitoring

Monitor full blood count closely along with liver, renal and mucosal status during and after administration.

Counselling the patient

Wash and change clothing and bedding frequently during treatment as advised to protect your skin.
Report fever, bleeding, bruising or mouth soreness promptly.
Use reliable contraception and discuss fertility preservation before treatment.

Evidence & guidelines

Use is guided by the manufacturer's SPC and established transplant conditioning protocols.

Reference: SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Drugs

Pathways