Busulfan Fresenius Kabi
Alkylating agent for myeloablative conditioning before stem cell transplantation
Busulfan Fresenius Kabi contains the active substance busulfan, a potent alkylating agent used exclusively in hospital settings as part of conditioning regimens before hematopoietic stem cell transplantation (HSCT). By destroying existing bone marrow cells, busulfan prepares the body to receive a new transplant of bone marrow or blood stem cells. This medication is administered to adults, children, and neonates under strict medical supervision by specialist transplant physicians.
Quick Facts
Key Takeaways
- Busulfan is a powerful chemotherapy drug used exclusively as myeloablative conditioning before bone marrow or stem cell transplantation.
- It is administered as an intravenous infusion in a hospital transplant unit, always in combination with other agents such as cyclophosphamide, fludarabine, or melphalan.
- Profound myelosuppression (suppression of blood cell production) is the intended and expected effect of busulfan treatment.
- Serious potential complications include hepatic veno-occlusive disease (VOD/SOS), seizures, and pulmonary toxicity, requiring close monitoring throughout treatment.
- Busulfan is contraindicated in pregnancy and may cause permanent infertility in both men and women; fertility preservation should be discussed before treatment.
What Is Busulfan Fresenius Kabi and What Is It Used For?
Busulfan Fresenius Kabi contains the active substance busulfan, which belongs to a class of chemotherapy drugs known as alkylating agents. Alkylating agents work by chemically modifying DNA within cells, creating cross-links between DNA strands that prevent the cells from dividing and ultimately lead to cell death. Busulfan is particularly effective against hematopoietic (blood-forming) stem cells in the bone marrow, making it an essential component of myeloablative conditioning regimens.
The primary purpose of busulfan therapy is to completely ablate (destroy) the patient's existing bone marrow before a transplant. This serves two critical functions: first, it eliminates diseased or malfunctioning bone marrow cells, and second, it creates space in the bone marrow niche for the new donor stem cells to engraft and begin producing healthy blood cells. Without effective conditioning, the transplanted stem cells would face competition from the patient's remaining marrow and might fail to establish themselves.
Busulfan Fresenius Kabi is approved for use across all age groups. In adults, it is used in combination with either cyclophosphamide (the classical BuCy regimen) or fludarabine (the BuFlu regimen, increasingly preferred due to its reduced toxicity profile). In neonates, infants, children, and adolescents (0-17 years), busulfan is combined with either cyclophosphamide or melphalan, depending on the underlying condition and transplant protocol.
Hematopoietic stem cell transplantation with busulfan-based conditioning is used to treat a range of serious conditions, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), myelodysplastic syndromes (MDS), severe aplastic anemia, thalassemia major, sickle cell disease, and various primary immunodeficiency disorders. The specific conditioning regimen chosen depends on the patient's diagnosis, age, overall health status, and the type of transplant (autologous or allogeneic).
Busulfan Fresenius Kabi is always administered in a specialized transplant center by healthcare professionals experienced in stem cell transplantation. You will receive this preparative medicine before you receive a transplant of either bone marrow or hematopoietic (blood-forming) stem cells.
What Should You Know Before Taking Busulfan Fresenius Kabi?
Contraindications
There are strict situations in which Busulfan Fresenius Kabi must not be used. Understanding these contraindications is essential for patient safety:
- Hypersensitivity: Do not use Busulfan Fresenius Kabi if you are allergic to busulfan or any of the other ingredients in this medicine (dimethylacetamide and macrogol 400).
- Pregnancy: Busulfan is contraindicated if you are pregnant or suspect you may be pregnant. Busulfan is teratogenic and embryotoxic in animal studies, meaning it can cause birth defects and harm the developing fetus.
Warnings and Precautions
Busulfan Fresenius Kabi is a powerful cytotoxic (cell-killing) medication that produces a profound and intended reduction in all blood cell counts. This myelosuppression is the desired therapeutic effect at the recommended dose, as it prepares the bone marrow to receive the transplant. However, this means that careful and frequent monitoring of blood counts, liver function, and overall clinical status is required throughout treatment and beyond.
It is important to understand that the use of busulfan may increase the risk of developing a secondary malignancy (cancer) in the future. This is a known long-term risk associated with alkylating agents, and your transplant team will discuss this with you as part of the risk-benefit assessment before proceeding with transplantation.
You should inform your doctor about any of the following conditions before receiving busulfan:
- Liver disease: Busulfan is metabolized by the liver, and pre-existing liver problems can increase the risk of hepatotoxicity, including the potentially life-threatening hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS).
- Kidney problems: Impaired kidney function may affect drug clearance and increase the risk of toxicity.
- Heart or lung problems: Busulfan can cause cardiac and pulmonary complications, and pre-existing conditions in these organs require special consideration.
- History of seizures: Busulfan lowers the seizure threshold. Patients with a history of epilepsy or seizure disorders are at increased risk, and prophylactic anticonvulsant therapy is mandatory before starting busulfan.
- Current medications: Many drugs can interact with busulfan, potentially increasing toxicity or reducing effectiveness.
Blood clots can form in the small blood vessels of the liver after hematopoietic cell transplantation (HCT), particularly when high-dose busulfan is given together with other conditioning agents. This condition, known as veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), can be life-threatening. Symptoms include rapid weight gain, abdominal pain, liver enlargement, and jaundice. Report any of these symptoms to your medical team immediately.
Pregnancy, Breastfeeding, and Fertility
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before receiving Busulfan Fresenius Kabi. The implications for reproductive health are significant and should be thoroughly discussed before treatment begins.
Pregnancy: Women must not be pregnant during treatment with busulfan and for up to 6 months after treatment. Busulfan is known to be teratogenic, meaning it can cause serious birth defects. Effective contraception must be used by both partners when either partner is being treated with busulfan.
Breastfeeding: Women must stop breastfeeding before beginning treatment with Busulfan Fresenius Kabi. It is not known whether busulfan passes into breast milk, but given its cytotoxic nature, breastfeeding during treatment poses an unacceptable risk to the infant.
Fertility: There is a significant risk that busulfan treatment may cause permanent infertility. In women, busulfan can cause premature ovarian failure, leading to symptoms of menopause and the inability to conceive. In young girls, busulfan may prevent the onset of puberty. Men treated with busulfan are advised not to father a child during and for up to 6 months after treatment. Sperm banking and egg/embryo freezing should be discussed with your medical team before treatment if future fertility is desired.
How Does Busulfan Fresenius Kabi Interact with Other Drugs?
Drug interactions are a critical consideration with busulfan therapy. Because busulfan has a narrow therapeutic window (the difference between an effective dose and a toxic dose is small), even modest changes in its blood levels can have significant clinical consequences. Increased busulfan exposure raises the risk of severe toxicity, particularly hepatic veno-occlusive disease, while decreased exposure may lead to graft failure.
Tell your doctor or pharmacist about all medications you are currently taking, have recently taken, or might take. This includes prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. The following interactions are particularly important:
Major Interactions
| Drug | Type | Effect | Recommendation |
|---|---|---|---|
| Itraconazole | Antifungal | Inhibits busulfan clearance, increasing plasma levels and risk of toxicity (VOD/SOS) | Avoid concurrent use; use alternative antifungal if possible |
| Metronidazole | Antibiotic/antiprotozoal | Increases busulfan trough levels by approximately 80%, significantly raising toxicity risk | Avoid use during busulfan treatment; use alternative antimicrobial |
| Paracetamol (Acetaminophen) | Analgesic/antipyretic | May decrease busulfan clearance via glutathione depletion, increasing toxicity risk | Avoid within 72 hours before or during busulfan treatment |
| Deferasirox | Iron chelator | May increase busulfan exposure and hepatotoxicity risk | Discontinue at least 48 hours before conditioning starts |
| Ketobemidone | Opioid analgesic | May increase the extent of busulfan side effects | Use with caution; consider alternative pain management |
Other Important Interactions
Cyclophosphamide: When used in the BuCy conditioning regimen, the order and timing of busulfan and cyclophosphamide administration is critical. Busulfan may affect the metabolism of cyclophosphamide, potentially altering its activation to its cytotoxic metabolite. The established protocols carefully define the sequence and interval between these agents.
Phenytoin: Phenytoin is commonly administered as prophylactic anticonvulsant therapy before busulfan. However, phenytoin is a potent enzyme inducer that can increase busulfan clearance, potentially reducing its efficacy. When phenytoin is used, busulfan dose adjustments may be necessary based on therapeutic drug monitoring. Benzodiazepines (such as clonazepam or lorazepam) may be used as alternatives that do not affect busulfan metabolism.
Thioguanine: Prior or concurrent use of thioguanine with busulfan may increase the risk of hepatic nodular regenerative hyperplasia, portal hypertension, and esophageal varices. This combination requires careful risk-benefit assessment.
What Is the Correct Dosage of Busulfan Fresenius Kabi?
The dosage of Busulfan Fresenius Kabi is always calculated individually based on the patient's body weight and the specific conditioning protocol being followed. Busulfan is administered as an intravenous infusion in a hospital transplant unit, and all doses are prepared and given by trained healthcare professionals. Therapeutic drug monitoring (TDM) of busulfan blood levels is commonly performed to optimize dosing and reduce the risk of both under-exposure (which may lead to graft failure) and over-exposure (which increases toxicity).
Adults
Busulfan + Cyclophosphamide (BuCy Regimen)
- Dose: 0.8 mg/kg per infusion
- Infusion duration: 2 hours per dose
- Frequency: Every 6 hours (4 doses per day)
- Duration: 4 consecutive days before transplantation (total 16 doses)
- Followed by: Cyclophosphamide, then transplant
Busulfan + Fludarabine (BuFlu Regimen)
- Dose: 3.2 mg/kg per infusion (once daily)
- Infusion duration: 3 hours per dose
- Frequency: Once daily
- Duration: 2 to 3 consecutive days before transplantation
- Followed by: Fludarabine, then transplant
Children and Adolescents (0-17 Years)
In neonates, infants, children, and adolescents, the recommended dose of Busulfan Fresenius Kabi in combination with cyclophosphamide or melphalan is weight-based and varies between 0.8 mg/kg and 1.2 mg/kg per dose. The specific dose is determined by the child's actual body weight, and dosing adjustments are made according to established pediatric transplant protocols. Therapeutic drug monitoring is particularly important in the pediatric population, as busulfan pharmacokinetics can be highly variable in children.
| Body Weight | Dose (mg/kg) | Frequency | Infusion Time |
|---|---|---|---|
| < 9 kg | 1.0 mg/kg | Every 6 hours | 2 hours |
| 9 to < 16 kg | 1.2 mg/kg | Every 6 hours | 2 hours |
| 16 to 23 kg | 1.1 mg/kg | Every 6 hours | 2 hours |
| > 23 to 34 kg | 0.95 mg/kg | Every 6 hours | 2 hours |
| > 34 kg | 0.8 mg/kg | Every 6 hours | 2 hours |
Pre-Medications
Before receiving Busulfan Fresenius Kabi, you will be given several pre-medications to prevent potential complications:
- Anticonvulsants: Seizure-preventing medications such as phenytoin or benzodiazepines (e.g., clonazepam) are administered starting before the first busulfan dose and continued for at least 24 hours after the last dose. This is mandatory because busulfan significantly lowers the seizure threshold.
- Antiemetics: Medications to prevent nausea and vomiting are given before each busulfan infusion, as nausea is a very common side effect of the drug.
Overdose
There is no specific antidote for busulfan overdose. The principal toxic effect of an overdose would be profound and prolonged myelosuppression with pancytopenia (critically low levels of all blood cell types). In the event of an overdose, supportive care including blood product transfusions, growth factor support, and aggressive treatment of infections would be required. Dialysis is not effective for removing busulfan due to its rapid tissue distribution.
What Are the Side Effects of Busulfan Fresenius Kabi?
Like all medicines, Busulfan Fresenius Kabi can cause side effects, although not everybody gets them. It is important to understand that many of the effects listed below are expected consequences of the myeloablative conditioning process and the transplantation itself, rather than unexpected adverse reactions. Your transplant team will monitor you closely and provide treatment for any side effects that occur.
The most serious side effects of busulfan treatment include profound myelosuppression (the intended effect), infections (resulting from the suppressed immune system), hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS, a liver condition involving blockage of small hepatic veins), graft-versus-host disease (GVHD, where the transplanted cells attack the recipient's body), and pulmonary complications including interstitial pneumonitis. Your doctor will regularly monitor your blood values and liver enzymes to detect and treat these conditions promptly.
Very Common
May affect more than 1 in 10 patients
- Blood: Decreased red blood cells, white blood cells, and platelets (myelosuppression)
- Infections: Bacterial, viral, and fungal infections due to immunosuppression
- Nervous system: Insomnia, anxiety, dizziness, depression
- Metabolism: Loss of appetite, decreased magnesium, calcium, potassium, phosphate, albumin; increased blood sugar
- Heart/Circulation: Increased heart rate, high or low blood pressure, vasodilation, blood clots
- Lungs: Shortness of breath, rhinitis, sore throat, cough, hiccups, nosebleeds, abnormal breath sounds
- Gastrointestinal: Nausea, mouth inflammation (mucositis), vomiting, abdominal pain, diarrhea, constipation, heartburn, anal discomfort, fluid in the abdomen (ascites)
- Liver: Enlarged liver, jaundice, hepatic veno-occlusive disease (VOD/SOS)
- Skin: Rash, itching, hair loss (alopecia)
- Musculoskeletal: Back pain, muscle pain, joint pain
- Kidney: Increased creatinine, urinary discomfort, decreased urine output, blood in urine
- General: Fever, headache, weakness, chills, pain, allergic reactions, edema, chest pain, injection site reactions, mucosal inflammation
- Investigations: Elevated liver enzymes, weight gain
Common
May affect 1 in 10 to 1 in 100 patients
- Nervous system: Confusion, nervous system disorders
- Metabolism: Low blood sodium (hyponatremia)
- Heart: Abnormal heart rhythm (arrhythmia), pericardial effusion or inflammation, decreased cardiac output
- Lungs: Increased respiratory rate, respiratory failure, alveolar hemorrhage, asthma, lung collapse (atelectasis), pleural effusion
- Gastrointestinal: Esophageal inflammation, ileus (bowel paralysis), vomiting blood
- Skin: Skin color changes, redness (erythema), skin peeling
- Kidney: Elevated blood urea nitrogen, moderate kidney impairment
Uncommon
May affect 1 in 100 to 1 in 1,000 patients
- Nervous system: Delirium, nervousness, hallucinations, agitation, encephalopathy, cerebral hemorrhage, seizures
- Heart/Circulation: Femoral artery thrombosis, extra heartbeats, decreased heart rate, capillary leak syndrome
- Lungs: Decreased blood oxygen (hypoxia)
- Gastrointestinal: Stomach and/or intestinal bleeding
Frequency Not Known
Cannot be estimated from available data
- Gonadal dysfunction (reduced function of reproductive glands)
- Visual disturbances including lens opacification (cataracts) and corneal thinning
- Symptoms of menopause and infertility in women
- Brain abscess, skin infections, disseminated (widespread) infection
- Liver disease
- Increased lactate dehydrogenase (LDH) in blood
- Increased blood uric acid and urea
- Incomplete tooth development (in children)
- Pulmonary arterial hypertension
Contact your transplant team immediately if you experience: sudden weight gain, abdominal pain or swelling, yellowing of the skin or eyes (jaundice), difficulty breathing, persistent fever, unusual bleeding or bruising, seizures, or confusion. These may be signs of serious complications requiring urgent treatment.
How Should You Store Busulfan Fresenius Kabi?
Proper storage of Busulfan Fresenius Kabi is essential to maintain the drug's stability and ensure patient safety. As this medication is handled exclusively in hospital pharmacies and transplant units, storage is managed by trained healthcare professionals. However, understanding the storage requirements helps ensure quality control at all stages.
Unopened vials: Store in a refrigerator at 2°C to 8°C. Keep the vials in the outer carton to protect from light. Do not freeze. Do not use the medication after the expiry date printed on the label and carton (EXP).
Diluted solution (after preparation): Once diluted with glucose 5% (50 mg/mL) or sodium chloride 0.9% (9 mg/mL) injection solution, chemical and physical stability has been demonstrated for:
- At room temperature (25°C ± 2°C): 8 hours including infusion time
- Refrigerated (2-8°C) then room temperature: 12 hours refrigerated followed by 3 hours at room temperature (25°C ± 2°C) including infusion time
The diluted solution must not be frozen. Only clear, colorless solutions without visible particles should be used. Any unused medicine or waste material should be disposed of according to local requirements for cytotoxic agents.
Keep this medicine out of the sight and reach of children. Medicines should not be disposed of via wastewater or household waste. These measures help protect the environment and prevent accidental exposure.
What Does Busulfan Fresenius Kabi Contain?
Understanding the composition of Busulfan Fresenius Kabi helps healthcare professionals ensure proper preparation and identify potential sources of hypersensitivity reactions. The formulation has been designed to maintain busulfan in a stable solution suitable for intravenous administration.
Active substance: The active ingredient is busulfan. Each milliliter of concentrate contains 6 mg busulfan:
- 10 mL vial contains 60 mg busulfan
- 40 mL vial contains 240 mg busulfan
After dilution to the recommended concentration, each mL of the infusion solution contains approximately 0.5 mg busulfan.
Other ingredients (excipients):
- Dimethylacetamide (DMA): A polar aprotic solvent used to dissolve busulfan in the concentrate. DMA enables the poorly water-soluble busulfan to remain in solution.
- Macrogol 400 (Polyethylene glycol 400): A co-solvent that stabilizes the busulfan solution and improves its compatibility with intravenous diluents.
Appearance and packaging: Busulfan Fresenius Kabi is a clear, colorless, viscous concentrate for solution for infusion. It is supplied in colorless glass vials (Type I) with a shrink-wrap cover. After dilution, the solution is a clear, colorless preparation. Packages contain either 8 vials of 10 mL or 1 vial of 40 mL.
Busulfan must be diluted before administration. The diluent volume should be 10 times the concentrate volume to achieve a final concentration of approximately 0.5 mg/mL. Polycarbonate infusion components must not be used due to incompatibility. Only non-polycarbonate syringes and infusion sets should be used. Strict aseptic technique is required, and cytotoxic handling precautions must be followed.
Frequently Asked Questions About Busulfan Fresenius Kabi
Busulfan Fresenius Kabi is used as part of conditioning (preparative) treatment before hematopoietic stem cell transplantation (HSCT). It destroys the existing bone marrow to create space for newly transplanted stem cells. It is used in adults, children, and neonates, typically combined with cyclophosphamide, fludarabine, or melphalan depending on the patient's age and diagnosis.
The most common side effects (affecting more than 1 in 10 patients) include myelosuppression (decreased blood cells, which is the intended effect), infections, nausea, vomiting, diarrhea, mouth inflammation (mucositis), liver enzyme elevation, skin rash, hair loss, fever, weakness, and insomnia. Hepatic veno-occlusive disease (VOD/SOS) is a serious but less common complication that requires close monitoring.
Busulfan Fresenius Kabi is administered as an intravenous infusion (drip) in a hospital transplant unit. It is never self-administered. The concentrate is diluted by the hospital pharmacy and given through a central venous catheter. Each infusion lasts 2-3 hours depending on the regimen. Blood levels of busulfan are often measured to ensure optimal dosing (therapeutic drug monitoring).
Yes, busulfan has several clinically significant drug interactions. Itraconazole, metronidazole, deferasirox, and ketobemidone can increase busulfan levels, raising toxicity risk. Paracetamol (acetaminophen) should be avoided within 72 hours before or during busulfan treatment. Phenytoin, used as a seizure prophylaxis, can increase busulfan clearance and may require dose adjustments. Always inform your medical team about all medications you are taking.
No, busulfan is contraindicated during pregnancy. It is teratogenic and can cause serious birth defects. Women must not be pregnant during treatment and for at least 6 months afterward. Both male and female patients must use effective contraception during and for 6 months after treatment. Busulfan may also cause permanent infertility, so fertility preservation options (egg freezing, sperm banking) should be discussed before treatment.
Unopened vials should be stored in a refrigerator at 2-8°C. After dilution, the solution is stable for up to 8 hours at room temperature (25°C) including infusion time, or 12 hours refrigerated followed by 3 hours at room temperature. The diluted solution must not be frozen. Only clear, colorless solutions without particles should be used.
References
- European Medicines Agency (EMA). Busulfan Fresenius Kabi - Summary of Product Characteristics (SmPC). www.ema.europa.eu. Accessed February 2026.
- Andersson BS, Thall PF, Madden T, et al. Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia. Biology of Blood and Marrow Transplantation. 2002;8(9):477-485. doi:10.1053/bbmt.2002.v8.pm12374452
- Bartelink IH, Lalmohamed A, van Reij EM, et al. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. The Lancet Haematology. 2016;3(11):e526-e536. doi:10.1016/S2352-3026(16)30114-4
- European Society for Blood and Marrow Transplantation (EBMT). EBMT Handbook on Haemopoietic Stem Cell Transplantation. 7th edition. 2019. www.ebmt.org.
- Palmer J, McCune JS, Perales MA, et al. Personalizing Busulfan-Based Conditioning: Considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biology of Blood and Marrow Transplantation. 2016;22(11):1915-1925. doi:10.1016/j.bbmt.2016.07.013
- World Health Organization (WHO). WHO Model List of Essential Medicines - 23rd List, 2023. www.who.int.
- Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014;124(3):344-353. doi:10.1182/blood-2014-02-514778
- Mohty M, Malard F, Abecassis M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplantation. 2016;51(7):906-912. doi:10.1038/bmt.2016.130
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, which consists of licensed specialist physicians in hematology, oncology, and transplant medicine. Our editorial process follows international medical guidelines from the WHO, EMA, EBMT, and FDA. All medical claims are supported by peer-reviewed evidence and follow the GRADE evidence framework.
All content is reviewed by board-certified hematologists and oncologists with clinical experience in stem cell transplantation. Our review process ensures accuracy, currency, and clinical relevance of all information presented.
We follow Evidence Level 1A standards, basing our content on systematic reviews, meta-analyses, and randomized controlled trials. Sources include EMA SmPC documentation, EBMT guidelines, and peer-reviewed journals.
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