[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Alkylating agents](https://durgical.com/en/pharmacology/classes/alkylating-agents/) › Thiotepa

# Thiotepa

## Alkylating agents?

Alkylating agents

## High alert?

An error with this medicine can cause serious harm: double checks and protocols are used.

## Pregnancy: contraindicated?

Contraindicated in pregnancy (EU label). Thiotepa can harm the fetus: effective contraception is used during treatment and for a time afterwards by women and by men with partners…

An old ethylenimine alkylating drug: used in stem cell transplant conditioning, in some solid tumours and instilled into the bladder.

Updated Nov 12, 2026

Also called: triethylenethiophosphoramide

## Quick facts

**Group**
[Alkylating agents](https://durgical.com/en/pharmacology/classes/alkylating-agents/)

**Target**
DNA (guanine N7), cross-linked by thiotepa and its active metabolite TEPA

**Used for**
With busulfan · Adenocarcinoma of the breast

**Key effects**
Nausea · Tiredness · Hair loss

**Monitor**
Complete blood count before · Skin of the groin

**ATC**
L01AC01

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

Thiotepa carries three ethylenimine (aziridine) rings that alkylate DNA bases and cross-link strands. Liver enzymes CYP3A4 and CYP2B6 convert it to TEPA, an active metabolite. Damaged DNA blocks replication and kills dividing cells, including bone marrow cells, which is why high doses need a stem cell transplant afterwards.

- CYP3A4 and CYP2B6 convert thiotepa to active TEPA
- Aziridine rings alkylate and cross-link DNA
- Dividing cells, tumour and marrow, die

## Indications

- With busulfan and cyclophosphamide to prepare children with class 3 beta-thalassaemia for allogeneic stem cell transplantation (reduces graft rejection). [Thalassemias (α and β) →](https://durgical.com/en/conditions/thalassemias/)
- Adenocarcinoma of the breast. [Breast cancer →](https://durgical.com/en/conditions/breast-cancer/)
- Adenocarcinoma of the ovary. [Ovarian cancer →](https://durgical.com/en/conditions/ovarian-cancer/)
- Superficial papillary carcinoma of the urinary bladder (instilled into the bladder). [Bladder cancer →](https://durgical.com/en/conditions/bladder-cancer/)
- Malignant effusions in the pleural, pericardial or peritoneal cavity. [Pleural effusion →](https://durgical.com/en/conditions/pleural-effusion/)

## Adverse effects

### Common

- Nausea, vomiting, loss of appetite, abdominal pain
- Tiredness, dizziness, headache, blurred vision
- Hair loss
- Pain at the injection site
- Bladder use: painful or frequent urination, blood in the urine

### Serious (rare, important)

- Severe myelosuppression with infection or bleeding (boxed warning)
- Carcinogenicity: second cancers (boxed warning)
- Skin toxicity: discoloration, blistering and peeling, worst in skin folds and under dressings
- Hypersensitivity, including anaphylaxis

## Contraindications

- Severe hypersensitivity to thiotepa
- Live or attenuated vaccines at the same time
- Pregnancy (EU label)

## Key interactions

**Strong CYP3A4 inhibitors (itraconazole, clarithromycin, ritonavir) or inducers (rifampicin, phenytoin)**
Change conversion to TEPA and so its efficacy and toxicity; avoided.

**CYP2B6 substrates**
Thiotepa inhibits CYP2B6 and can raise their exposure.

**Live or attenuated vaccines**
Contraindicated: risk of serious infection in a suppressed immune system.

## What is monitored

- Complete blood count before and during treatment
- Skin of the groin, armpits, neck and skin folds
- Signs of infection or bleeding
- Liver and kidney function

## Administration and safety

- Hazardous cytotoxic: prepared and handled with protective measures.
- Several routes (vein, bladder, body cavities): the route is checked against the order.
- High-dose use: the patient showers or bathes and occlusive dressings and bed sheets are changed often during and shortly after treatment, because the drug leaves through the skin.
- Skin that touches the solution is washed thoroughly with soap and water.

## Pregnancy and breastfeeding

Contraindicated in pregnancy (EU label). Thiotepa can harm the fetus: effective contraception is used during treatment and for a time afterwards by women and by men with partners who could conceive, and breastfeeding is stopped.

## Nursing care

- Check blood counts before each treatment and teach to report fever, sore throat, bleeding or bruising.
- Help with frequent bathing and dressing changes; inspect skin folds for redness or peeling.
- Watch for allergic reactions during administration.
- With bladder instillation: teach to keep the solution in the bladder for the prescribed time and to report pain or blood in the urine.
- Counsel on infertility and contraception for women and men.

## Pharmacokinetics

**Absorption**
Given into a vein, into the bladder or into the pleural, pericardial or peritoneal cavity.

**Metabolism**
Liver, by CYP3A4 and CYP2B6, to the active metabolite TEPA.

**Elimination**
Part is excreted through the skin at high doses.

## Memory aid

«Thio-TEPA, three rings»: three aziridine rings grab DNA, and TEPA keeps working after the liver converts it.

## Test yourself

Think of the answer, then tap the question to see it.

## Which active metabolite of thiotepa is formed in the liver?

TEPA, formed by CYP3A4 and CYP2B6.

## Why are frequent baths and dressing changes needed after high-dose thiotepa?

Thiotepa and its metabolites are excreted through the skin and can burn it, especially in folds and under dressings.

## Which vaccines are contraindicated with thiotepa?

Live or attenuated vaccines.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/thiotepa/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**High alert**
An error with this medicine can cause serious harm: double checks and protocols are used.

**Pregnancy: contraindicated**
Contraindicated in pregnancy (EU label). Thiotepa can harm the fetus: effective contraception is used during treatment and for a time afterwards by women and by men with partners…

## Connections

## Related drugs 3

- [Cyclophosphamide](https://durgical.com/en/pharmacology/cyclophosphamide/)
- [Melphalan](https://durgical.com/en/pharmacology/melphalan/)
- [Bendamustine](https://durgical.com/en/pharmacology/bendamustine/)

## Related conditions 5

- [Thalassemias (α and β)](https://durgical.com/en/conditions/thalassemias/)
- [Breast cancer](https://durgical.com/en/conditions/breast-cancer/)
- [Ovarian cancer](https://durgical.com/en/conditions/ovarian-cancer/)
- [Bladder cancer](https://durgical.com/en/conditions/bladder-cancer/)
- [Pleural effusion](https://durgical.com/en/conditions/pleural-effusion/)

[← Back to the class: Alkylating agents](https://durgical.com/en/pharmacology/classes/alkylating-agents/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - THIOTEPA injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b3b21d90-96e3-48c0-a816-00c6636f3ce6) (DailyMed (U.S. National Library of Medicine), 2026); [Thiotepa Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682821.html) (MedlinePlus (U.S. National Library of Medicine), 2025); [EMA: product information for thiotepa](https://www.ema.europa.eu/en/documents/product-information/tepadina-epar-product-information_en.pdf) (European Medicines Agency, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01AC01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/thiotepa/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/thiotepa/