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Busulfex Side Effects

Generic Name: busulfan

Note: This document contains side effect information about busulfan. Some of the dosage forms listed on this page may not apply to the brand name Busulfex.

For the Consumer

Applies to busulfan: intravenous solution

Along with its needed effects, busulfan (the active ingredient contained in Busulfex) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking busulfan:

More Common

  • Black, tarry stools
  • bloated abdomen or stomach
  • blood in the urine or stools
  • blurred vision
  • chest pain
  • cough or hoarseness
  • dizziness
  • fast or irregular breathing
  • fast, pounding, or irregular heartbeat or pulse
  • fever or chills
  • headache
  • lower back or side pain
  • nervousness
  • pain and fullness in the upper abdominal or stomach
  • painful or difficult urination
  • pinpoint red spots on the skin
  • pounding in the ears
  • skin rash or itching
  • slow heartbeat
  • swelling of the eyes or eyelids
  • tightness in the chest
  • trouble breathing
  • unusual bleeding or bruising
  • weight gain
  • yellow eyes and skin

Incidence Not Known

Some side effects of busulfan may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More Common

  • Acid or sour stomach
  • back pain
  • belching
  • bloody nose
  • depression
  • diarrhea
  • difficulty having a bowel movement (stool)
  • fear
  • heartburn
  • indigestion
  • loss of appetite
  • lack or loss of strength
  • sneezing
  • stomach discomfort or upset
  • stuffy nose or runny nose
  • swelling or inflammation of the mouth
  • tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over affected area
  • trouble sleeping

For Healthcare Professionals

Applies to busulfan: intravenous solution, oral tablet


Hematologic side effects including myelosuppression resulting in leukopenia, thrombocytopenia and anemia, comprise the most frequent toxic effects that have been reported with the use of busulfan (the active ingredient contained in Busulfex) Dose limiting myelosuppression is the main side effect with usual doses. Postmarketing reports have included febrile neutropenia and thrombotic microangiopathy.[Ref]

Myelosuppression can develop suddenly and may be prolonged, but is usually reversible. Myelosuppression is most frequently the result of a failure to discontinue further drug administration in the face of an undetected decrease in leukocyte or platelet counts. During high dose therapy, neutrophils start to increase on approximately the 19th day and platelets on approximately the 30th day. In one study, four out of 243 patients treated with busulfan developed leukemia.[Ref]


Corticosteroids have been reported to have been beneficial in arresting or reversing the fibrosis in some cases.[Ref]

Respiratory side effects including lung damage have frequently been reported (approximately 33% of patients with the higher doses used for bone marrow transplant). While reported only rarely, interstitial pulmonary fibrosis (busulfan lung) warrants the immediate discontinuation of busulfan administration. Presentation of symptoms is delayed by several years in many patients. There is a slow onset of cough, dyspnea and low grade fever. (However, the clinician needs to rule out infection or leukemia in the lungs.) Next, patients may present with pulmonary insufficiency, tachypnea and cyanosis which may eventually be fatal. A single case of pulmonary alveolar proteinosis has also been reported.[Ref]


The case of endocardial fibrosis was reported in a 79-year-old woman who received a total dose of 7,200 mg over a period of 9 years for the management of chronic myelogenous leukemia. At autopsy, she was found to have endocardial fibrosis of the left ventricle in addition to interstitial pulmonary fibrosis.[Ref]

Cardiovascular side effects including mild or moderate tachycardia have been reported in 44% of patients. In 7 patients (11%) it was first reported during busulfan administration. Other rhythm abnormalities, which were all mild or moderate, included arrhythmia (5%), atrial fibrillation (2%), ventricular extrasystoles (2%), and third degree heart block (2%).

Mild or moderate thrombosis occurred in 33% of patients. (All episodes were associated with the central venous catheter.)

Hypertension (36%), mild vasodilation (flushing and hot flashes) (25%), and hypotension (11%) have also been reported.

Other cardiovascular events included cardiomegaly (5%), mild ECG abnormality (2%), Grade 3/4 left-sided heart failure in one patient (2%), and moderate pericardial effusion (2%). (These events were reported primarily in the post-cyclophosphamide phase.)

One case of endocardial fibrosis has been reported.[Ref]


Ocular side effects including cataracts and vision changes have been reported rarely after prolonged administration.[Ref]

The drug has also been reported to induced cataracts in rats.[Ref]


In one study, 31 out of 65 patients that received busulfan (the active ingredient contained in Busulfex) prior to bone marrow transplantation had some degree of alopecia. In 19 of these patients, the alopecia was extensive. While all patients received the same dosage per kg, patients that had higher blood concentrations developed more extensive alopecia.

Hyperpigmentation has most frequently been reported in patients with a dark complexion.

Some cases of alopecia have been permanent.[Ref]

Dermatologic side effects including hyperpigmentation (usually seen in skin folds near nails and hands) have been reported (5% to 10%). Urticaria, erythema multiforme, erythema nodosum, alopecia, porphyria cutanea tarda, and excessive dryness and fragility of the skin with anhidrosis have also been reported.[Ref]


The symptoms of the syndrome (which resembles adrenal insufficiency) have sometimes been reversible after the drug has been withdrawn. Adrenal responsiveness to exogenously administered ACTH has usually been normal. However, pituitary function testing with metyrapone revealed a blunted 17-hydroxycorticosteroid excretion in two patients. Following the discontinuation of the drug (which was associated with clinical improvement), rechallenge with metyrapone revealed normal pituitary-adrenal function.

Adverse effects due to the increased urate pool can be minimized by increased hydration, urine alkalinization and the prophylactic administration of a xanthine oxidase inhibitor (e.g., allopurinol).[Ref]

Metabolic side effects including several cases of a clinical syndrome closely resembling adrenal insufficiency, characterized by weakness, severe fatigue, anorexia, weight loss, melanoderma, nausea, and vomiting, have been reported after prolonged therapy. Postmarketing reports have included tumor lysis syndrome.

While hyperuricemia and/or hyperuricosuria are not uncommon in patients with chronic myelogenous leukemia, additional rapid destruction of granulocytes may accompany the initiation of chemotherapy and increase the urate pool.[Ref]


Based on clinical examination and laboratory findings, hepatic veno-occlusive disease was diagnosed in 8% (5/61) of patients treated with busulfan (the active ingredient contained in Busulfex) in the setting of allogeneic transplantation, was fatal in 2/5 cases (40%), and yielded an overall mortality from hepatic veno-occlusive disease in the entire study population of 2/61 (3%).[Ref]

Hepatic side effects including hepatic veno-occlusive disease have been reported. Esophageal varices have been reported in patients receiving busulfan in combination with thioguanine. Jaundice and hepatitis have also been reported.[Ref]

Nervous system

Nervous system side effects including seizures have generally been reported after the third or fourth day in patients receiving high dose therapy.[Ref]

In one study of 28 bone marrow transplant recipients that had received busulfan, 3 cases of convulsions have been reported. Two of the 3 patients that experienced the convulsions had been pretreated with anticonvulsants. Another study reported 2 patients out of 130 experienced seizures. There have been 16 cases of busulfan-related seizures reported in the literature. Prophylactic anticonvulsant therapy (phenytoin) should be considered in patients receiving high dose busulfan.[Ref]


Oncologic side effects including cytologic and histologic changes in the urinary and respiratory tracts as well as the uterine cervix and liver have been reported. The International Agency for Research on Cancer (IARC) has classified the activity of busulfan (the active ingredient contained in Busulfex) as sufficient to indicate potential carcinogenicity (in short-term tests). Two cases of endometrial cancer have been reported (each case followed two years of treatment).[Ref]


Other side effects in patients receiving allogenic transplant were some form of edema (79%), hypervolemia, or documented weight increase (8%). All events were reported as mild or moderate.


Genitourinary side effects including hemorrhagic cystitis, gynecomastia, amenorrhea, ovarian and testicular atrophy (resulting in sterility) have been reported.[Ref]


Gastrointestinal side effects including dryness of the oral mucous membranes and cheilosis have been reported.[Ref]


Musculoskeletal side effects including myasthenia gravis have been reported.[Ref]


Postmarketing reports have included severe bacterial, viral (e.g.,cytomegalovirus viremia) and fungal infections; and sepsis.


1. Stott H, Fox W, Girling DJ, Stephens RJ, Galton DA "Acute leukaemia after busulphan." Br Med J 2 (1977): 1513-7

2. "Toxic effects of busulphan." Lancet 1 (1968): 854

3. "Product Information. Myleran (busulfan)." Glaxo Wellcome, Research Triangle Park, NC.

4. "Multum Information Services, Inc. Expert Review Panel"

5. Fernandez LA, Zayed E "Busulfan-induced sideroblastic anemia." Am J Hematol 28 (1988): 199-200

6. Littler WA, Kay JM, Hasleton PS, Heath D "Busulphan lung." Thorax 24 (1969): 639-55

7. Burns WA, McFarland W, Matthews MJ "Toxic manifestations of busulfan therapy." Med Ann Dist Columbia 40 (1971): 567-72

8. Littler WA, Ogilvie C "Lung function in patients receiving busulphan." Br Med J 4 (1970): 530-2

9. Feingold ML, Koss LG "Effects of long-term administration of busulfan. Report of a patient with generalized nuclear abnormalities, carcinoma of vulva, and pulmonary fibrosis." Arch Intern Med 124 (1969): 66-71

10. Burns WA, McFarland W, Matthews MJ "Busulfan-induced pulmonary disease. report of a case and review ofthe literature." Am Rev Respir Dis 101 (1970): 408-13

11. Manning DM, Strimlan CV, Turbiner EH "Early detection of busulfan lung: report of a case." Clin Nucl Med 5 (1980): 412-4

12. Comhaire F, Van Hove W, Van Ganse W, Van der Straeten M "Busulphan and the lungs. Absence of lung function disturbance in patients treated with busulphan." Scand J Respir Dis 53 (1972): 265-73

13. Kirschner RH, Esterly JR "Pulmonary lesions associated with busulfan therapy of chronic myelogenous leukemia." Cancer 27 (1971): 1074-80

14. Podoll LN, Winkler SS "Busulfan lung. Report of two cases and review of the literature." Am J Roentgenol Radium Ther Nucl Med 120 (1974): 151-6

15. Sostman HD, Matthay RA, Putman CE "Cytotoxic drug-induced lung disease." Am J Med 62 (1977): 608-15

16. Pearl M "Busulfan lung." Am J Dis Child 131 (1977): 650-2

17. Dahlgren S, Holm G, Svanborg N, Watz R "Clinical and morphological side-effects of busulfan (Myleran) treatment." Acta Med Scand 192 (1972): 129-35

18. Woodliff HJ, Finlay-Jones LR "Busulphan lung." Med J Aust 2 (1972): 719-22

19. Littler WA "Busulphan lung: clinical features." Thorax 25 (1970): 257

20. Ward HN, Konikov N, Reinhard EH "Cytologic dysplasia occurring after busulfan (Myleran) therapy. A syndrome resembling adrenocortical insufficiency and atrophic bronchitis." Ann Intern Med 63 (1965): 654-60

21. Weinberger A, Pinkhas J, Sandbank U, Shaklai M, de Vries A "Endocardial fibrosis following busulfan treatment." JAMA 231 (1975): 495

22. Ravindranathan MP, Paul VJ, Kuriakose ET "Cataract after busulphan treatment." Br Med J 1 (1972): 218-9

23. Tosti A, Piraccini BM, Vincenzi C, Misciali C "Permanent alopecia after busulfan chemotherapy." Br J Dermatol 152 (2005): 1056-8

24. Sprunt JG, Rizza CR "Pigmentation and busulphan therapy." Br Med J 5489 (1966): 736-7

25. Vivacqua RJ, Haurani FI, Erslev AJ ""Selective" pituitary insufficiency secondary to busulfan." Ann Intern Med 67 (1967): 380-7

26. Harrold BP "Syndrome resembling Addison's disease following prolonged treatment with busulphan." Br Med J 5485 (1966): 463-4

27. Grochow LB "Busulfan disposition: the role of therapeutic monitoring in bone marrow transplantation induction regimens." Semin Oncol 20 (4 Suppl) (1993): 18-25;quiz26

28. Underwood JC, Shahani RT, Blackburn EK "Cholestatic jaundice following treatment of chronic granulocytic leukemia with busulphan." J Clin Pathol 23 (1970): 827

29. Underwood JC, Shahani RT, Blackburn EK "Jaundice after treatment of leukemia with busulphan." Br Med J 1 (1971): 556-7

30. Hasegawa S, Horibe K, Kawabe T, Kato K, Kojima S, Matsuyama T, Hirabayashi N "Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors." Bone Marrow Transplant 22 (1998): 1191-7

31. Morris LE, Guthrie TH Jr "Busulfan-induced hepatitis." Am J Gastroenterol 83 (1988): 682-3

32. Vassal G, Hartmann O, Benhamou E "Busulfan and veno-occlusive disease of the liver." Ann Intern Med 112 (1990): 881

33. Marcus RE, Goldman JM "Convulsions due to high-dose busulphan." Lancet 2 (1984): 1463

34. Martell RW, Sher C, Jacobs P, Monteagudo F "High-dose busulfan and myoclonic epilepsy." Ann Intern Med 106 (1987): 173

35. De La Camara R, Tomas JF, Figuera A, Berberana M, Fernandez-Ranada JM "High dose busulfan and seizures." Bone Marrow Transplant 7 (1991): 363-4

36. Buggia I, Locatelli F, Regazzi MB, Zecca M "Busulfan." Ann Pharmacother 28 (1994): 1055-62

37. Sureda A, Perez de Oteyza J, Garcia Larana J, Odriozola J "High-dose busulfan and seizures." Ann Intern Med 111 (1989): 543-4

38. Murphy CP, Harden EA, Thompson JM "Generalized seizures secondary to high-dose busulfan therapy." Ann Pharmacother 26 (1992): 30-1

39. Aksoy M, Erdem S, Bakioglu I, Dincol G "Endometrial cancer due to busulfan therapy. Report of two cases." J Cancer Res Clin Oncol 108 (1984): 362-3

40. Bishop JB, Wassom JS "Toxicological review of busulfan (Myleran)." Mutat Res 168 (1986): 15-45

41. Hussey HH "Editorial: Gynecomastia." JAMA 228 (1974): 1423

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.