Thiotepa Fresenius Kabi
Alkylating agent for conditioning before bone marrow transplant
Quick Facts: Thiotepa Fresenius Kabi
Key Takeaways About Thiotepa Fresenius Kabi
- Conditioning for transplant: Thiotepa is used exclusively to prepare patients for bone marrow or stem cell transplantation by destroying existing marrow cells
- Hospital-only treatment: This medication is always administered as an intravenous infusion by specialized healthcare professionals in a hospital transplant unit
- Profound immunosuppression: The drug causes significant reduction in blood cell counts, requiring close monitoring and supportive care including anti-infective prophylaxis
- Fertility impact: Thiotepa can impair fertility in both men and women; sperm banking and genetic counselling should be discussed before treatment begins
- Used in adults and children: Thiotepa can be used across all age groups, with dosing calculated individually based on body surface area or weight
What Is Thiotepa Fresenius Kabi and What Is It Used For?
Thiotepa Fresenius Kabi contains the active substance thiotepa, an alkylating chemotherapy agent used as conditioning treatment before haematopoietic stem cell transplantation (HSCT). It works by cross-linking DNA strands in bone marrow cells, destroying them to create space for new transplanted stem cells.
Thiotepa belongs to a group of medicines called alkylating agents, which are among the oldest classes of cytotoxic drugs used in cancer therapy. The alkylating mechanism involves the formation of covalent bonds with DNA molecules, leading to cross-links between DNA strands that prevent cell replication and ultimately cause cell death. This property makes thiotepa particularly valuable in the transplant setting, where the goal is to ablate the patient's existing bone marrow.
The primary clinical indication for Thiotepa Fresenius Kabi is as part of the conditioning regimen prior to haematopoietic progenitor cell transplantation (HPCT). In this context, conditioning refers to the intensive chemotherapy (and sometimes radiotherapy) given to a patient before they receive transplanted stem cells. The purpose of conditioning is threefold: to eliminate residual disease, to create physical space within the bone marrow for the donor cells to engraft, and to suppress the patient's immune system sufficiently to prevent rejection of the transplanted cells.
Thiotepa can be used in both autologous transplantation (where the patient receives their own previously harvested stem cells) and allogeneic transplantation (where the stem cells come from a matched donor). It is commonly used in conditioning regimens for haematological malignancies including leukaemias, lymphomas, and myelodysplastic syndromes, as well as for certain solid tumours in paediatric patients.
The drug has a long clinical history dating back to its first synthesis in the 1950s. It is listed in the European Medicines Agency (EMA) database of approved medicinal products and is recognized by the World Health Organization (WHO) as an essential component of transplant conditioning protocols. Thiotepa can be used in both adults and children, with the dose calculated individually by the treating physician based on the patient's body surface area or weight and the specific disease being treated.
What Should You Know Before Receiving Thiotepa?
Before receiving thiotepa, patients must undergo a thorough medical evaluation. The drug is contraindicated in pregnancy, during breastfeeding, and in patients with known hypersensitivity to thiotepa. Live vaccines must not be administered during treatment.
Contraindications
Thiotepa must not be used if you are allergic (hypersensitive) to thiotepa or any of the other ingredients. It is absolutely contraindicated during pregnancy or if there is any possibility of pregnancy, and during breastfeeding. Vaccination with live viral or bacterial vaccines, including yellow fever vaccine, is prohibited during treatment with thiotepa and for a period after treatment, as the profoundly immunosuppressed state could allow uncontrolled replication of the vaccine organism, potentially leading to serious or fatal infections.
Before starting treatment, your healthcare team will perform a comprehensive assessment including blood tests, liver function tests, kidney function tests, cardiac evaluation, and pulmonary function assessment. This baseline evaluation is essential because thiotepa can affect the function of all these organ systems. Any pre-existing impairment must be carefully considered when planning the conditioning regimen.
Warnings and Precautions
You must inform your doctor if you have any of the following conditions, as they may require special monitoring or dose adjustments:
- Liver or kidney problems: Thiotepa is metabolized in the liver and excreted partially through the kidneys. Impaired function of either organ can lead to increased drug exposure and toxicity.
- Heart or lung problems: The conditioning process places significant stress on the cardiovascular and pulmonary systems. Pre-existing disease increases the risk of serious complications.
- Seizure disorders (epilepsy): Thiotepa can lower the seizure threshold. If you are being treated with phenytoin or fosphenytoin for epilepsy, your levels will need close monitoring as thiotepa may affect anticonvulsant metabolism.
Because thiotepa destroys bone marrow cells responsible for producing blood cells, you will have regular blood tests during treatment to monitor your blood cell counts. This profound myelosuppression is an expected and intended effect of the drug, but it means you will be at significantly increased risk of infections, bleeding, and anaemia. To prevent and treat infections, you will receive prophylactic antimicrobial medications.
Pregnancy, Breastfeeding, and Fertility
Thiotepa is known to be teratogenic (harmful to the developing foetus) and must not be used during pregnancy. If you are of childbearing potential, a pregnancy test must be performed before starting treatment, and effective contraception must be used throughout the treatment period.
After treatment ends, women must continue using effective contraception for at least 6 months, and men for at least 3 months. It is unknown whether thiotepa passes into breast milk, so breastfeeding is not permitted during treatment as a precautionary measure.
Thiotepa can impair fertility in both men and women. Male patients should seek advice about sperm cryopreservation (sperm banking) before starting treatment. If there is a desire to have children after completing treatment, genetic counselling is recommended beforehand, as alkylating agents can cause genetic damage to reproductive cells.
Driving and Operating Machinery
Some side effects of thiotepa, including dizziness, headache, and blurred vision, may impair your ability to drive or operate machinery. If you experience any of these effects, you should not drive or use machines until the symptoms resolve. During the transplant period, patients are typically hospitalized and this consideration is mainly relevant during the post-discharge recovery phase.
How Does Thiotepa Interact with Other Drugs?
Thiotepa interacts with several medications, most notably other myelosuppressive agents used in conditioning regimens, anticonvulsants like phenytoin, and live vaccines. All concomitant medications must be reviewed by the transplant team before treatment begins.
Because thiotepa is always administered in a controlled hospital setting as part of a conditioning regimen, drug interactions are carefully managed by the transplant team. However, it is essential that you inform your doctor about all medications you are taking, including over-the-counter medicines, herbal supplements, and vitamins.
Major Interactions
The most clinically significant drug interactions with thiotepa involve the following categories:
| Interacting Drug | Type | Clinical Effect | Management |
|---|---|---|---|
| Live vaccines (yellow fever, BCG, MMR) | Contraindicated | Risk of uncontrolled vaccine organism replication and fatal infection due to immunosuppression | Absolutely prohibited during and after treatment until immune reconstitution |
| Cyclophosphamide | Potentiation | Inhibits metabolism of thiotepa leading to increased toxicity; combined myelosuppressive effect | Dose adjustment and close monitoring required when used together in conditioning |
| Busulfan | Additive | Additive myelosuppression and increased risk of veno-occlusive disease (VOD) of the liver | Commonly used together in conditioning; requires hepatic monitoring |
| Phenytoin / Fosphenytoin | Metabolic | Thiotepa may affect phenytoin metabolism, altering seizure control | Monitor phenytoin levels closely; dose adjustment may be needed |
| Fludarabine | Additive | Additive immunosuppression and myelosuppression | Used together in some conditioning protocols with appropriate supportive care |
Additional Considerations
Thiotepa is metabolized primarily by the cytochrome P450 enzyme system, particularly CYP2B6 and CYP3A4. Any medication that significantly inhibits or induces these enzymes may alter thiotepa exposure. Strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, and certain protease inhibitors) may increase thiotepa levels, while strong inducers (such as rifampicin, carbamazepine, and phenobarbital) may reduce its efficacy. Your transplant team will review all medications for potential interactions before initiating treatment.
It is also important to note that thiotepa's immunosuppressive effects persist well beyond the treatment period itself. During the period of immune reconstitution following transplant, certain medications and vaccinations may need to be withheld or their timing carefully planned in coordination with the transplant team. Inactivated vaccines can generally be administered once sufficient immune recovery has occurred, typically 3-6 months post-transplant, but live vaccines are usually delayed until at least 24 months after transplant.
What Is the Correct Dosage of Thiotepa?
The dose of thiotepa is calculated individually by the treating physician based on the patient's body surface area or weight, the underlying disease, and the transplant protocol. Thiotepa is given as an intravenous infusion lasting 2-4 hours, every 12 or 24 hours for up to 5 days.
Unlike many other medications where standard fixed doses are prescribed, the dosing of thiotepa is entirely individualized and protocol-dependent. The transplant centre will follow established conditioning protocols that specify the exact thiotepa dose, timing, and combination with other agents. The dose varies significantly depending on whether the transplant is autologous or allogeneic, the type of disease being treated, and the patient's characteristics.
Adults
Adult Dosing
In adult patients, the thiotepa dose is typically calculated based on body surface area (BSA) and varies by conditioning protocol. Doses in the context of myeloablative conditioning typically range from 5-10 mg/kg total dose, divided over several days. The exact regimen depends on the specific protocol being followed, which may include other chemotherapy agents such as busulfan, cyclophosphamide, or fludarabine.
Each infusion is administered intravenously over 2 to 4 hours by qualified healthcare professionals. The drug must be reconstituted and then further diluted before infusion, and it is always delivered through an in-line 0.2-micron filter.
Children and Adolescents
Paediatric Dosing
Thiotepa is approved for use in paediatric patients. As with adults, the dose is calculated individually based on the child's body surface area or weight and the specific disease indication. Paediatric conditioning protocols may use different total doses and schedules compared to adult regimens, reflecting the different tolerability and disease biology in younger patients. Close monitoring is particularly important in children, including tracking of growth and development during long-term follow-up.
Elderly Patients
Elderly Dosing Considerations
There is limited clinical experience with thiotepa in elderly patients (over 65 years). When used in this population, particular attention must be paid to pre-existing organ function, comorbidities, and overall performance status. Reduced-intensity conditioning regimens may be considered for older patients, though this is a decision made by the transplant team based on the individual patient's clinical profile. Dose adjustments may be necessary based on renal and hepatic function.
Administration Schedule
| Parameter | Details |
|---|---|
| Route | Intravenous infusion only |
| Infusion duration | 2 to 4 hours per infusion |
| Frequency | Every 12 or 24 hours |
| Treatment duration | Up to 5 days |
| Setting | Hospital transplant unit only |
| Preparation | Reconstitution with sterile water, then dilution with 0.9% sodium chloride |
| Filter | 0.2 micrometer in-line filter required |
Missed Dose
Because thiotepa is administered in a closely monitored hospital setting as part of a precisely timed conditioning regimen, missed doses are not a practical concern in the same way as with outpatient medications. However, if a dose is delayed or missed for any reason, the transplant team will determine how to proceed based on the overall conditioning protocol and the clinical situation. It is critical that the conditioning regimen is completed as planned to ensure adequate marrow ablation before transplantation.
Overdose
There is no specific antidote for thiotepa overdose. In the event of an overdose, the primary concern would be exaggerated myelosuppression, leading to potentially fatal pancytopenia (loss of all blood cell types). Management would be supportive, including aggressive anti-infective therapy, blood product transfusion, and potentially emergency stem cell transplantation. The narrow therapeutic window of thiotepa underscores the importance of precise dose calculation and verification by the transplant team.
What Are the Side Effects of Thiotepa?
Thiotepa causes significant side effects, many of which are expected consequences of its mechanism of action. The most serious include profound myelosuppression, infection, liver toxicity including veno-occlusive disease, and graft-versus-host disease (in allogeneic transplant). Your medical team will closely monitor for and proactively manage these effects.
Like all chemotherapy agents, thiotepa can cause a wide range of side effects. It is important to understand that many of these effects, particularly the reduction in blood cell counts, are an intended part of the conditioning process. Your transplant team has extensive experience managing these effects, and a comprehensive supportive care plan will be in place throughout your treatment. Not all patients experience all side effects, and severity can vary considerably between individuals.
Very Common
Affects more than 1 in 10 patients
- Increased susceptibility to infection and sepsis
- Decreased white blood cells, platelets, and red blood cells (anaemia)
- Graft-versus-host disease (in allogeneic transplant)
- Dizziness, headache, blurred vision
- Seizures (convulsions)
- Tingling, numbness, or pins-and-needles sensation (paraesthesia)
- Cardiac arrest, cardiac arrhythmia
- Nausea, vomiting, diarrhoea
- Mucositis (inflammation of the mouth lining)
- Inflammation of the stomach, oesophagus, or colon
- Loss of appetite (anorexia), high blood sugar
- Skin rash, itching, skin peeling, skin colour changes, redness (erythema)
- Hair loss (alopecia)
- Back pain, abdominal pain, muscle and joint pain
- Lung inflammation, enlarged liver, liver function disorders
- Veno-occlusive disease of the liver (VOD)
- Jaundice (yellowing of skin and eyes)
- High blood pressure, abnormal electrolytes
- Fever, chills, general weakness, weight gain
- Bleeding, nosebleeds, oedema (fluid retention)
- Pain or inflammation at injection site
- Eye infection (conjunctivitis), hearing impairment
- Reduced sperm count, vaginal bleeding, absent menstruation
- Memory loss, confusion
- Delayed growth in children
- Bladder dysfunction, reduced testosterone, thyroid or pituitary insufficiency
Common
Affects up to 1 in 10 patients
- Anxiety, confusion
- Intracranial aneurysm (abnormal bulging of a brain artery)
- Elevated creatinine levels
- Allergic reactions
- Blood clots (embolism)
- Heart rhythm disorders, heart failure, cardiovascular insufficiency
- Oxygen deficiency, pulmonary oedema, lung bleeding
- Respiratory arrest
- Blood in urine (haematuria), bladder inflammation
- Difficulty urinating, decreased urine output
- Elevated blood urea nitrogen (BUN)
- Cataracts
- Liver failure, brain haemorrhage
- Cough, constipation, bowel obstruction
- Stomach perforation
- Muscle tone changes, severely impaired coordination
- Bruising, menopausal symptoms
- Secondary cancer (malignancy)
- Abnormal brain function
- Male and female infertility
Uncommon
Affects up to 1 in 100 patients
- Skin inflammation and scaling (erythrodermic psoriasis)
- Delirium, nervousness, hallucinations, agitation
- Gastrointestinal ulceration
- Inflammation of the heart muscle (myocarditis)
- Heart disease (cardiomyopathy)
Frequency Not Known
Reported but frequency cannot be established
- Pulmonary arterial hypertension (elevated blood pressure in lung arteries)
- Severe skin damage (severe lesions, large blisters) potentially covering the entire body surface, which can be life-threatening
- Leukoencephalopathy (damage to brain white matter), which can be life-threatening
The most serious complications of thiotepa-based conditioning include veno-occlusive disease (VOD) of the liver, a condition where small blood vessels in the liver become blocked, leading to liver damage. Symptoms of VOD include weight gain from fluid retention, pain in the upper right abdomen, jaundice, and ascites (fluid accumulation in the abdomen). Early detection and treatment of VOD is critical, and your transplant team will monitor liver function tests regularly.
Graft-versus-host disease (GVHD) is another major complication seen after allogeneic transplantation, where the transplanted immune cells recognize the recipient's tissues as foreign and mount an immune attack. GVHD can affect the skin, liver, and gastrointestinal tract. Prophylactic immunosuppressive medications are given to minimize the risk, but GVHD remains a significant cause of morbidity and mortality after allogeneic HSCT.
How Should Thiotepa Fresenius Kabi Be Stored?
Thiotepa Fresenius Kabi must be stored and transported at 2-8°C (refrigerated) and must not be frozen. After reconstitution, the solution is stable for 8 hours at 2-8°C. After dilution, it is stable for 24 hours at 2-8°C and 4 hours at 25°C.
Keep this medicine out of the sight and reach of children. Do not use after the expiry date stated on the carton and vial label (after "EXP"). The expiry date refers to the last day of that month. As a cytotoxic agent, thiotepa requires careful handling and proper disposal procedures. All unused medicine and waste material should be disposed of in accordance with local requirements for cytotoxic waste.
| Stage | Temperature | Stability |
|---|---|---|
| Unopened vial | 2-8°C (refrigerated) | Until expiry date; do not freeze |
| After reconstitution | 2-8°C | 8 hours |
| After dilution (refrigerated) | 2-8°C | 24 hours |
| After dilution (room temp) | 25°C | 4 hours |
From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, in-use storage times and conditions before use are the responsibility of the user and should normally not exceed 24 hours at 2-8°C. These storage requirements are primarily relevant to hospital pharmacy staff, as patients will not handle the drug themselves.
What Does Thiotepa Fresenius Kabi Contain?
The active substance is thiotepa. Thiotepa Fresenius Kabi is available as 15 mg and 100 mg vials of white powder or cake that must be reconstituted before use. The only excipient is sodium carbonate.
Thiotepa Fresenius Kabi is presented as a sterile white powder or cake in a glass vial. The product must be reconstituted with sterile water for injections before it can be administered. The 15 mg vial is reconstituted with 1.5 mL of sterile water, and the 100 mg vial with 10 mL, yielding a concentration of 10 mg/mL in both cases.
After reconstitution, the solution is hypotonic and must be further diluted before administration. The reconstituted solution is diluted with 500 mL of 0.9% sodium chloride solution for injection (or 1000 mL if the dose exceeds 500 mg) to achieve a final thiotepa concentration between 0.5 and 1 mg/mL. Only colourless solutions without particles should be used; reconstituted solutions may sometimes appear opalescent, which is acceptable.
The infusion solution must be administered using an infusion set equipped with a 0.2-micrometer in-line filter. Before and after each infusion, the indwelling catheter should be flushed with approximately 5 mL of 0.9% sodium chloride solution. Each carton contains one single-use vial.
Frequently Asked Questions About Thiotepa Fresenius Kabi
Thiotepa Fresenius Kabi is used as conditioning treatment to prepare patients for haematopoietic stem cell transplantation (bone marrow transplant). It works by destroying existing bone marrow cells using its alkylating mechanism, which creates space for new transplanted stem cells to engraft and produce healthy blood cells. It is used in both adults and children for various haematological malignancies and certain solid tumours.
Thiotepa is given as an intravenous infusion (drip into a vein) by qualified healthcare professionals in a hospital transplant unit. Each infusion lasts 2 to 4 hours. You will receive infusions every 12 or 24 hours for up to 5 days. The drug must be reconstituted and diluted before use and is administered through a special filter. You will never need to handle or administer this medication yourself.
The most common side effects include increased susceptibility to infections, decreased blood cell counts (expected from the conditioning process), nausea, vomiting, diarrhoea, mucositis (mouth sores), hair loss, fever, and skin changes. Serious complications can include liver toxicity (veno-occlusive disease), graft-versus-host disease, and lung problems. Your transplant team will monitor you closely and has extensive experience managing these effects.
Yes, thiotepa can significantly impair fertility in both men and women. Male patients should strongly consider sperm cryopreservation (sperm banking) before starting treatment. After treatment, women must use effective contraception for at least 6 months and men for at least 3 months. If you wish to have children after completing treatment, genetic counselling is recommended. Your transplant team will discuss these important considerations with you before treatment begins.
Yes, thiotepa can be used in children and adolescents as part of conditioning treatment before stem cell transplantation. The dose is calculated individually by the treating physician based on the child's body surface area or weight and the specific disease being treated. Children receive the same careful monitoring as adult patients, with additional attention to growth and developmental milestones during long-term follow-up.
Thiotepa Fresenius Kabi must be stored refrigerated at 2-8°C and must not be frozen. After reconstitution, the solution remains stable for 8 hours at 2-8°C. After further dilution for infusion, it is stable for 24 hours at 2-8°C or 4 hours at room temperature (25°C). In practice, this is managed entirely by the hospital pharmacy and nursing team; patients do not need to store this medication at home.
References
All information in this article is based on international medical guidelines and peer-reviewed research. The following sources were consulted:
- European Medicines Agency (EMA). Thiotepa - Summary of Product Characteristics. Updated 2024. Available at: www.ema.europa.eu
- World Health Organization (WHO). WHO Model List of Essential Medicines - 23rd List, 2023. Geneva: WHO; 2023.
- European Society for Blood and Marrow Transplantation (EBMT). EBMT Handbook: Haematopoietic Stem Cell Transplantation and Cellular Therapies. 7th Edition, 2019. Available at: doi.org/10.1007/978-3-030-02278-5
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Cell Transplantation. Version 2.2024.
- Przepiorka D, et al. "Thiotepa-based conditioning for allogeneic transplantation." Biology of Blood and Marrow Transplantation. 2020;26(3):S190-S191.
- Fresenius Kabi. Thiotepa Fresenius Kabi - Package Information Leaflet. Last updated July 2024.
- British National Formulary (BNF). Thiotepa monograph. BMJ Group and Pharmaceutical Press, 2024.
- Mohty M, et al. "Busulfan plus thiotepa as a myeloablative conditioning regimen before allogeneic stem cell transplantation." Blood. 2020;136(Supplement 1):38-39.
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