Busulfan

Busulfan is a bifunctional alkylating agent in which two labile methanesulfonate groups are attached to opposite ends of a four-carbon alkyl chain. In aqueous media, busulfan hydrolyzes to release the methanesulfonate groups.

• Busulfan injection is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.ICD-10: C95.90

• Busulfan is contraindicated in patients with a history of hypersensitivity to any of its components.contraindicated

Pre-medicate with anticonvulsants (e.g. benzodiazepines, phenytoin, valproic acid or levetiracetam) and antiemetic ( 2.1 , 5.2 ) Dilute and administer as intravenous infusion. Do not administer as intravenous push or bolus ( 2.1 , 2.3 ) Recommended adult dose: 0.8 mg per kg of ideal body weight or actual body weight, whichever is lower, administered intravenously via a central venous catheter as a two-hour infusion every six hours for four consecutive days for a total of 16 doses ( 2.1 ) 2.1 Initial Dosing Information • Administer busulfan injection in combination with cyclophosphamide as a conditioning regimen prior to bone marrow or peripheral blood progenitor cell replacement. For patients weighing more than 12 kg, the recommended doses are: o Busulfan injection 0.8 mg per kg (ideal body weight or actual body weight, whichever is lower) intravenously via a central venous catheter as a two-hour infusion every six hours for four consecutive days for a total of 16 doses (Days -7, -6, -5 and -4). o Cyclophosphamide 60 mg per kg intravenously as a one-hour infusion on each of two days beginning no sooner than six hours following the 16 th dose of busulfan injection (Days -3 and -2). o Administer hematopoietic progenitor cells on Day 0. • Premedicate patients with anticonvulsants (e.g., benzodiazepines, phenytoin, valproic acid or levetiracetam) to prevent seizures reported with the use of high dose busulfan injection. Administer anticonvulsants 12 hours prior to busulfan injection to 24 hours after the last dose of busulfan injection [see Warnings and Precautions (5.2) ].

Seizures: Initiate anticonvulsant prophylactic therapy prior to treatment with busulfan. Monitor patients with history of seizure disorder, head trauma or receiving epileptogenic drugs ( 5.2 ) Hepatic Veno-Occlusive Disease (HVOD): Increased risk of developing HVOD at AUC greater than 1,500 µM·min. Monitor serum transaminases, alkaline phosphatase and bilirubin daily ( 5.3 ) Embryo-fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception ( 5.4 , 8.1 , 8.3 ) Cardiac tamponade has been reported in pediatric patients with thalassemia who received high doses of oral busulfan and cyclophosphamide. Abdominal pain and vomiting preceded the tamponade in most patients ( 5.5 ) 5.1 Myelosuppression The most frequent serious consequence of treatment with busulfan at the recommended dose and schedule is prolonged myelosuppression, occurring in all patients (100%). Severe granulocytopenia, thrombocytopenia, anemia, or any combination thereof may develop. Hematopoietic progenitor cell transplantation is required to prevent potentially fatal complications of the prolonged myelosuppression. Monitor complete blood counts, including white blood cell differentials, and quantitative platelet counts daily during treatment and until engraftment is demonstrated . Absolute neutrophil counts dropped below 0.5x10 9 /L at a median of 4 days post-transplant in 100% of patients treated in the busulfan clinical trial.

The following adverse reactions are discussed in more detail in other sections of the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Seizures [see Warnings and Precautions (5.2) ] Hepatic Veno-Occlusive Disease (HVOD) [see Warnings and Precautions (5.3) ] Embryo-fetal Toxicity [see Warnings and Precautions (5.4) ] Cardiac Tamponade [see Warnings and Precautions (5.5) ] Bronchopulmonary Dysplasia [see Warnings and Precautions (5.6) ] Cellular Dysplasia [see Warnings and Precautions (5.7) ] Most common adverse reactions (incidence >60%) were: myelosuppression, nausea, stomatitis, vomiting, anorexia, diarrhea, insomnia, fever, hypomagnesemia, abdominal pain, anxiety, headache, hyperglycemia and hypokalemia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eugia US LLC at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reaction information is primarily derived from the clinical study (N=61) of busulfan and the data obtained for high-dose oral busulfan conditioning in the setting of randomized, controlled trials identified through a literature review.

Lactation: Advise women not to breastfeed ( 8.2 ) 8.1 Pregnancy Risk Summary Busulfan can cause fetal harm when administered to a pregnant woman based on animal data. Busulfan was teratogenic in mice, rats, and rabbits following administration during organogenesis. The solvent, DMA, may also cause fetal harm when administered to a pregnant woman. In rats, DMA doses of approximately 40% of the daily dose of DMA in the busulfan dose on a mg/m 2 basis given during organogenesis caused significant developmental anomalies ( see Data ). There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Animal Data Following administration during organogenesis in animals, busulfan caused malformations and anomalies, including significant alterations in the musculoskeletal system, body weight gain, and size. In pregnant rats, busulfan produced sterility in both male and female offspring due to the absence of germinal cells in the testes and ovaries.

Metabolism

The pharmacokinetics of busulfan were studied in 59 patients participating in a prospective trial of a busulfan-cyclophosphamide preparatory regimen prior to allogeneic hematopoietic progenitor stem cell transplantation. Patients received 0.8 mg/kg busulfan every six hours, for a total of 16 doses over four days.

There is no known antidote to busulfan other than hematopoietic progenitor cell transplantation. In the absence of hematopoietic progenitor cell transplantation, the recommended dosage for busulfan would constitute an overdose of busulfan. The principal toxic effect is profound bone marrow hypoplasia/aplasia and pancytopenia, but the central nervous system, liver, lungs, and gastrointestinal tract may be affected. Monitor hematologic status closely and institute vigorous supportive measures as medically indicated. Survival after a single 140 mg dose of Myleran ® Tablets in an 18 kg, 4-year old child has been reported. Inadvertent administration of a greater than normal dose of oral busulfan (2.1 mg per kg; total dose of 23.3 mg per kg) occurred in a 2-year old child prior to a scheduled bone marrow transplant without sequelae. An acute dose of 2.4 g was fatal in a 10-year old boy. There is one report that busulfan is dialyzable, thus dialysis should be considered in the case of overdose.

• Jun 26, 1954NDANDA009386Waylis Therap
• Feb 4, 1999NDANDA020954Otsuka Pharm
• Mar 24, 2017ANDAANDA207050Pharmascience Inc
• Dec 18, 2017ANDAANDA209580Amneal
• Jul 31, 2018ANDAANDA205672Hospira
• Feb 22, 2019ANDAANDA210148Accord Hlthcare Inc
• Apr 18, 2019ANDAANDA210931Shilpa
• Oct 23, 2020ANDAANDA212127Meitheal

Reference statistics from the openFDA drug-shortage dataset. For a live view, consult the FDA database directly. Not clinical guidance.

• Busulfan, Injection, 6 mg/1 mL (NDC 67457-893-08)To be discontinued
  Sponsor: Mylan Institutional, a Viatris Company
  Updated Oct 24, 2025

1. 1Off Label Use2,09512%
2. 2Product Use In Unapproved Indication1,82710%
3. 3Mucosal Inflammation1,1996.7%
4. 4Drug Ineffective1,0725.9%
5. 5Graft Versus Host Disease1,0525.8%
6. 6Acute Graft Versus Host Disease1,0365.7%
7. 7Venoocclusive Liver Disease1,0345.7%
8. 8Cytomegalovirus Infection9795.4%
9. 9Febrile Neutropenia9715.4%
10. 10Pyrexia9045.0%
11. 11Chronic Graft Versus Host Disease7634.2%
12. 12Sepsis7234.0%
13. 13Acute Graft Versus Host Disease In Skin6673.7%
14. 14Diarrhoea6523.6%
15. 15Infection6213.4%

Recent PubMed references pinned to Busulfan as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• A liquid chromatography-tandem mass spectrometry method for therapeutic drug monitoring of treosulfan.
  Laboratory medicine · 2026 · Ryu J, Kim S, Lee SH, et al.
  PMID 42048559DOI 10.1093/labmed/lmag017
• [Erjing Wan ameliorates busulfan-induced oligoasthenospermia in mice by inhibiting p38 MAPK/NF-κB pathway].
  Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · 2026 · Xie F, Yao GP, Peng M, et al.
  PMID 42011621DOI 10.19540/j.cnki.cjcmm.20251210.705
• Busulfan pharmacokinetics in adults - a real-world evaluation of intra-individual variability and the impact of obesity and deferasirox.
  Bone marrow transplantation · 2026 · Langebrake C, Wansing EA, Janson D, et al.
  PMID 41981079DOI 10.1038/s41409-026-02833-0
• Treosulfan-fludarabine conditioning in infants with severe combined immunodeficiencies: Extended study of the UK paediatric treosulfan study.
  British journal of haematology · 2026 · Lum SH, Greener S, Memon IL, et al.
  PMID 41958357DOI 10.1111/bjh.70453
• Intra-ovarian busulfan administration: an effective and relatively safe method for depleting endogenous germ cells in the female marine teleost yellow drum (Nibea albiflora).
  Fish physiology and biochemistry · 2026 · Zhang Z, Yu L, Yang Y, et al.
  PMID 41902885DOI 10.1007/s10695-026-01668-2
• Efficacy and safety profile of busulfan plus low-dose melphalan (BUMEL) versus high-dose melphalan (MEL200) as a conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma patients: a systematic review and meta-analysis.
  Expert review of hematology · 2026 · Maqbool S, Khan I, Ibrahim M, et al.
  PMID 41860155DOI 10.1080/17474086.2026.2649831
• A Clinically Relevant Drug Interaction Between Busulfan and Rifampin in the Setting of Hematopoietic Stem Cell Transplant Conditioning.
  Pharmacology research & perspectives · 2026 · Drangines C, Laquet J, Kunwor R, et al.
  PMID 41826263DOI 10.1002/prp2.70230
• Refining busulfan exposure enhances pediatric ALL HSCT outcomes: insights from the International FORUM study.
  Blood advances · 2026 · Ben Hassine K, Gloor Y, Dupanloup I, et al.
  PMID 41779961DOI 10.1182/bloodadvances.2025019142

The 10 most recently updated of 778 ClinicalTrials.gov registrations naming Busulfan as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Efficacy and Safety of the CloB2M (Clofarabine Combined With Busulfan and Melphalan) Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients With Acute Myeloid Leukemia in First Complete Remission
  Not yet recruiting · Interventional · 30 enrolled · Institute of Hematology & Blood Diseases Hospital, China
  NCT07644481updated 2026-06-12
• Stem Cell Transplantation for Participants With Germline RUNX1 Associated Blood Cancers
  Not yet recruiting · Phase 2 · Interventional · 98 enrolled · National Cancer Institute (NCI)
  NCT07524530updated 2026-06-12
• A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006)
  Recruiting · Phase 3 · Interventional · 340 enrolled · Merck Sharp & Dohme LLC
  NCT06079879updated 2026-06-12
• Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease
  Recruiting · Phase 1 · Phase 2 · Interventional · 10 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT06325709updated 2026-06-11
• MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
  Recruiting · Phase 2 · Interventional · 2,000 enrolled · National Cancer Institute (NCI)
  NCT05564390updated 2026-06-11
• SHR2554/AZA + Overlapped Modified BUCY for High-risk/Relapsed Leukemia/MDS
  Not yet recruiting · Phase 2 · Interventional · 180 enrolled · The First Affiliated Hospital of Soochow University
  NCT07575412updated 2026-06-10
• Sorafenib, Busulfan and Fludarabine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia Undergoing Donor Stem Cell Transplant
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 74 enrolled · M.D. Anderson Cancer Center
  NCT03247088updated 2026-06-10
• Haplo-Cord HSCT for AML/MDS
  Recruiting · Interventional · 82 enrolled · Fujian Medical University Union Hospital
  NCT07588360updated 2026-06-10
• Human Leukocyte Antigen (HLA) Mismatched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation
  Recruiting · Phase 1 · Interventional · 29 enrolled · He Huang
  NCT06809712updated 2026-06-09
• Trial of Allogeneic Reduced-Intensity, HLA-Haploidentical Allogeneic Hematopoietic Cell Bone Marrow Transplantation Followed by Graft-versus-Host-Disease (GVHD) Prophylaxis With Cyclophosphamide, Bortezomib and Maraviroc for Hematologic Malignancies ...
  Recruiting · Phase 1 · Phase 2 · Interventional · 265 enrolled · National Cancer Institute (NCI)
  NCT05470491updated 2026-06-08

Frequently asked questions

How does Busulfan work?

Busulfan is a bifunctional alkylating agent in which two labile methanesulfonate groups are attached to opposite ends of a four-carbon alkyl chain. In aqueous media, busulfan hydrolyzes to release the methanesulfonate groups.

What is Busulfan used for?

According to FDA labeling, Busulfan carries indications including: Busulfan injection is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Busulfan?

Busulfan is classified as Alkyl sulfonates, Alkylating Drug, Alkylating Activity, Decreased DNA Integrity, Decreased DNA Replication.

What are the brand names for Busulfan?

Busulfan is marketed under brand names including Busulfex, Myleran.

What are the contraindications for Busulfan?

Busulfan labeling lists contraindications including: Busulfan is contraindicated in patients with a history of hypersensitivity to any of its components.. Always consult the full prescribing information and a clinician.