Busulfan
Generic name: busulfan · Brand names: Myleran, Busulfex (injection, not covered in main record)
Quick facts
Drug class
Busulfan is an alkylating agent, a type of chemotherapy drug.
Section
DESCRIPTION; MedlinePlus Why is this medication prescribed?
Source text (exact source wording)
MYLERAN (busulfan) is a bifunctional alkylating agent. [DESCRIPTION] // MedlinePlus: Busulfan is in a class of medications called alkylating agents.
Rx or otc
Rx per MedlinePlus wording ('Follow the directions on your prescription label'); formal Rx-only statement not extracted from label text, so treat as medium confidence
Forms and strengths
- MYLERAN is supplied as white, film-coated, round, biconvex tablets containing 2 mg busulfan in amber glass bottles with child-resistant closures. One side is imprinted with "GX EF3" and the other side is imprinted with an "M." Bottle of 25 (NDC 80725-620-25).
Generic available
Value
no
Source
DailyMed spls.json?drug_name=busulfan (10 entries): the only tablet entry is MYLERAN (Waylis Therapeutics LLC); all other entries are injections. This is a search result, not a statement from the FDA Orange Book.
Common use one line
Used for the palliative treatment of chronic myelogenous (myeloid, myelocytic, granulocytic) leukemia.
What it is used for
Myleran is used for palliative treatment of chronic myelogenous leukemia. It is the brand; no generic tablet was found. MedlinePlus also says busulfan tablets are used with other drugs before a bone marrow transplant, which the label's indication does not list.
Section
INDICATIONS AND USAGE
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Conflict
yes
Conflict note
MedlinePlus (Other uses) also says busulfan tablets are used in combination with other drugs to destroy the bone marrow and cancer cells in preparation for a bone marrow transplant. The Myleran label indication lists only palliative treatment of chronic myelogenous leukemia. Both kept.
Source text (exact source wording)
INDICATIONS AND USAGE MYLERAN (busulfan) is indicated for the palliative treatment of chronic myelogenous (myeloid, myelocytic, granulocytic) leukemia.
Medlineplus source text (exact source wording)
Busulfan is used treat a certain type of chronic myelogenous leukemia (CML; a type of cancer of the white blood cells). // Busulfan tablets are also used in combination with other drugs to destroy the bone marrow and cancer cells in preparation for a bone marrow transplant.
How it works
Busulfan alkylates DNA, and this is felt to be an important way it kills cells. It slows or stops the growth of cancer cells.
Section
CLINICAL PHARMACOLOGY, Biochemical Pharmacology; MedlinePlus
Source
Label and MedlinePlus
Source text (exact source wording)
Biochemical Pharmacology: In aqueous media, busulfan undergoes a wide range of nucleophilic substitution reactions. While this chemical reactivity is relatively non-specific, alkylation of the DNA is felt to be an important biological mechanism for its cytotoxic effect. // MedlinePlus: It works by slowing or stopping the growth of cancer cells in your body.
Dosage: adults
Busulfan is taken by mouth. The usual adult dose to start is 4 to 8 mg total daily. Daily doses above 4 mg are for patients with the most compelling symptoms. Treatment is stopped before the white blood cell count falls into the normal range, and the drug is withheld when the count reaches about 15,000/mcL. Maintenance of 1 to 3 mg daily may be used if remission lasts less than 3 months. Dosing is set and watched closely by the treating doctor.
Section
DOSAGE AND ADMINISTRATION
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
DOSAGE AND ADMINISTRATION Busulfan is administered orally. The usual adult dose range for remission induction is 4 to 8 mg, total dose, daily. Dosing on a weight basis is the same for both pediatric patients and adults, approximately 60 mcg/kg of body weight or 1.8 mg/m2 of body surface, daily. Since the rate of fall of the leukocyte count is dose related, daily doses exceeding 4 mg per day should be reserved for patients with the most compelling symptoms; the greater the total daily dose, the greater is the possibility of inducing bone marrow aplasia. A decrease in the leukocyte count is not usually seen during the first 10 to 15 days of treatment; the leukocyte count may actually increase during this period and it should not be interpreted as resistance to the drug, nor should the dose be increased. Since the leukocyte count may continue to fall for more than 1 month after discontinuing the drug, it is important that busulfan be discontinued prior to the total leukocyte count falling into the normal range. When the total leukocyte count has declined to approximately 15,000/mcL, the drug should be withheld. With a constant dose of busulfan, the total leukocyte count declines exponentially; a weekly plot of the leukocyte count on semi-logarithmic graph paper aids in predicting the time when therapy should be discontinued. With the recommended dose of busulfan, a normal leukocyte count is usually achieved in 12 to 20 weeks. During remission, the patient is examined at monthly intervals and treatment resumed with the induction dosage when the total leukocyte count reaches approximately 50,000/mcL. When remission is shorter than 3 months, maintenance therapy of 1 to 3 mg daily may be advisable in order to keep the hematological status under control and prevent rapid relapse.
Dosage: children
The label says dosing by weight is the same for children and adults, about 60 mcg/kg of body weight or 1.8 mg/m2 of body surface daily. The juvenile type of chronic myelogenous leukemia responds poorly to busulfan.
Section
DOSAGE AND ADMINISTRATION; Pediatric Use; Clinical Studies
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
DOSAGE AND ADMINISTRATION: Dosing on a weight basis is the same for both pediatric patients and adults, approximately 60 mcg/kg of body weight or 1.8 mg/m2 of body surface, daily. // Pediatric Use: See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections. // Clinical Studies: ... the so-called “juvenile” type of chronic myelogenous leukemia, typically occurring in young children and associated with the absence of a Philadelphia chromosome, responds poorly to busulfan.
Dosage adjustments
Drug interaction caps
The dose of busulfan may need to be lowered if it is used with other drugs that mainly cause bone marrow suppression.
Section
PRECAUTIONS, Laboratory Tests
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Laboratory Tests: The dosage of busulfan may need to be reduced if this agent is combined with other drugs whose primary toxicity is myelosuppression.
Kidney
The label says elimination of busulfan appears to be independent of kidney function. It gives no kidney dose adjustment.
Section
CLINICAL PHARMACOLOGY
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
CLINICAL PHARMACOLOGY: The elimination of busulfan appears to be independent of renal function. This probably reflects the extensive metabolism of the drug in the liver, since less than 2% of the administered dose is excreted in the urine unchanged within 24 hours.
Liver
Section
no label dose adjustment found for liver impairment
Elderly
Studies did not include enough people aged 65 and over to tell if they respond differently. Dose selection for an older person should be cautious, usually starting at the low end of the dosing range.
Section
PRECAUTIONS, Geriatric Use
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Geriatric Use Clinical studies of busulfan did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Missed dose
The Myleran label has no missed-dose instructions. MedlinePlus says to take the missed dose as soon as you remember it, unless it is almost time for the next dose, and never to take a double dose.
Source
MedlinePlus Busulfan (a682248)
Source text (exact source wording)
MedlinePlus: Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
Overdose
There is no known antidote. The main toxic effects are bone marrow depression and pancytopenia, and blood counts must be watched closely. In case of overdose, call poison control at 1-800-222-1222.
Section
OVERDOSAGE; MedlinePlus In case of emergency/overdose
Source
Label and MedlinePlus
Source text (exact source wording)
OVERDOSAGE There is no known antidote to busulfan. The principal toxic effects are bone marrow depression and pancytopenia. The hematologic status should be closely monitored and vigorous supportive measures instituted if necessary. Induction of vomiting or gastric lavage followed by administration of charcoal would be indicated if ingestion were recent. Dialysis may be considered in the management of overdose as there is 1 report of successful dialysis of busulfan (see CLINICAL PHARMACOLOGY). Gastrointestinal toxicity with mucositis, nausea, vomiting, and diarrhea has been observed when MYLERAN was used in association with bone marrow transplantation. // MedlinePlus: In case of overdose, call the poison control helpline at 1-800-222-1222.
Storage
Store at 25°C (77°F); brief excursions to 15° to 30°C (59° to 86°F) are allowed. Keep away from excess heat and moisture and not in the bathroom.
Section
HOW SUPPLIED; MedlinePlus storage
Source
Label and MedlinePlus
Labeler specific note
Waylis Therapeutics LLC label. Label also says: Procedures for proper handling and disposal of anticancer drugs should be considered.
Source text (exact source wording)
HOW SUPPLIED ... Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature). // MedlinePlus: Store it at room temperature and away from excess heat and moisture (not in the bathroom).
Boxed warning
Myleran is a potent drug. It should only be used when chronic myelogenous leukemia has been properly diagnosed and by a doctor who knows how to judge the response to chemotherapy. It can cause severe bone marrow hypoplasia, so the dose should be reduced or stopped right away at the first sign of a drop in blood cells. The label points to its Warnings section about busulfan-induced leukemia.
Section
WARNING (boxed warning, Myleran label)
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
WARNING MYLERAN is a potent drug. It should not be used unless a diagnosis of chronic myelogenous leukemia has been adequately established and the responsible physician is knowledgeable in assessing response to chemotherapy. MYLERAN can induce severe bone marrow hypoplasia. Reduce or discontinue the dosage immediately at the first sign of any unusual depression of bone marrow function as reflected by an abnormal decrease in any of the formed elements of the blood. A bone marrow examination should be performed if the bone marrow status is uncertain. SEE WARNINGS FOR INFORMATION REGARDING BUSULFAN-INDUCED LEUKEMOGENESIS IN HUMANS.
Contraindications
Not for people whose chronic myelogenous leukemia diagnosis has not been firmly established.
Section
CONTRAINDICATIONS
Source text (exact source wording)
MYLERAN is contraindicated in patients in whom a definitive diagnosis of chronic myelogenous leukemia has not been firmly established.
Not for people who have had an allergic reaction to busulfan or any other part of the tablet.
Section
CONTRAINDICATIONS
Source text (exact source wording)
MYLERAN is contraindicated in patients who have previously suffered a hypersensitivity reaction to busulfan or any other component of the preparation.
Warnings and precautions
The most serious common problem is bone marrow failure, which causes very low blood counts. It is usually caused by not stopping the drug soon enough. Recovery can take from 1 month to 2 years. Use extra caution if bone marrow was affected by earlier radiation or chemotherapy.
Heading
Bone marrow failure / pancytopenia
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
The most frequent, serious side effect of treatment with busulfan is the induction of bone marrow failure (which may or may not be anatomically hypoplastic) resulting in severe pancytopenia. The pancytopenia caused by busulfan may be more prolonged than that induced with other alkylating agents. It is generally felt that the usual cause of busulfan-induced pancytopenia is the failure to stop administration of the drug soon enough; individual idiosyncrasy to the drug does not seem to be an important factor. MYLERAN should be used with extreme caution and exceptional vigilance in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy, or whose marrow function is recovering from previous cytotoxic therapy. Although recovery from busulfan-induced pancytopenia may take from 1 month to 2 years, this complication is potentially reversible, and the patient should be vigorously supported through any period of severe pancytopenia.
A rare but serious lung problem called pulmonary fibrosis can start from 8 months to 10 years after treatment begins. Signs include cough, trouble breathing and low-grade fever. There is no specific therapy and the drug should be stopped if it develops.
Heading
Pulmonary fibrosis (busulfan lung)
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
A rare, important complication of busulfan therapy is the development of bronchopulmonary dysplasia with pulmonary fibrosis. Symptoms have been reported to occur within 8 months to 10 years after initiation of therapy—the average duration of therapy being 4 years. The histologic findings associated with “busulfan lung” mimic those seen following pulmonary irradiation. Clinically, patients have reported the insidious onset of cough, dyspnea, and low-grade fever. In some cases, however, onset of symptoms may be acute. Pulmonary function studies have revealed diminished diffusion capacity and decreased pulmonary compliance. It is important to exclude more common conditions (such as opportunistic infections or leukemic infiltration of the lungs) with appropriate diagnostic techniques. If measures such as sputum cultures, virologic studies, and exfoliative cytology fail to establish an etiology for the pulmonary infiltrates, lung biopsy may be necessary to establish the diagnosis. Treatment of established busulfan-induced pulmonary fibrosis is unsatisfactory; in most cases the patients have died within 6 months after the diagnosis was established. There is no specific therapy for this complication. MYLERAN should be discontinued if this lung toxicity develops. The administration of corticosteroids has been suggested, but the results have not been impressive or uniformly successful.
Busulfan may cause cell changes in many organs and chromosome changes. Cancers and acute leukemias have been reported in people who took busulfan, and the World Health Organization has concluded there is a causal link between busulfan and secondary cancers.
Heading
Cellular dysplasia, mutagenicity, secondary cancers
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
Busulfan may cause cellular dysplasia in many organs in addition to the lung. Cytologic abnormalities characterized by giant, hyperchromatic nuclei have been reported in lymph nodes, pancreas, thyroid, adrenal glands, liver, and bone marrow. This cytologic dysplasia may be severe enough to cause difficulty in interpretation of exfoliative cytologic examinations from the lung, bladder, breast, and the uterine cervix. In addition to the widespread epithelial dysplasia that has been observed during busulfan therapy, chromosome aberrations have been reported in cells from patients receiving busulfan. Busulfan is mutagenic in mice and, possibly, in humans. Malignant tumors and acute leukemias have been reported in patients who have received busulfan therapy, and this drug may be a human carcinogen. The World Health Organization has concluded that there is a causal relationship between busulfan exposure and the development of secondary malignancies. Four cases of acute leukemia occurred among 243 patients treated with busulfan as adjuvant chemotherapy following surgical resection of bronchogenic carcinoma. All 4 cases were from a subgroup of 19 of these 243 patients who developed pancytopenia while taking busulfan 5 to 8 years before leukemia became clinically apparent. These findings suggest that busulfan is leukemogenic, although its mode of action is uncertain.
Periods can stop and menopausal symptoms can occur in premenopausal women. Ovarian failure has been linked to busulfan, including failure to reach puberty in girls. Sterility, azoospermia and testicular atrophy have been reported in men.
Heading
Ovarian suppression and fertility
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
Ovarian suppression and amenorrhea with menopausal symptoms commonly occur during busulfan therapy in premenopausal patients. Busulfan has been associated with ovarian failure including failure to achieve puberty in females. Busulfan interferes with spermatogenesis in experimental animals, and there have been clinical reports of sterility, azoospermia, and testicular atrophy in male patients.
Life-threatening liver blood vessel blockage has been reported, usually when busulfan is given with cyclophosphamide or other chemotherapy before a bone marrow transplant. Liver blood tests are done to find problems early.
Heading
Hepatic veno-occlusive disease
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
Hepatic veno-occlusive disease, which may be life threatening, has been reported in patients receiving busulfan, usually in combination with cyclophosphamide or other chemotherapeutic agents prior to bone marrow transplantation. Possible risk factors for the development of hepatic veno-occlusive disease include: total busulfan dose exceeding 16 mg/kg based on ideal body weight, and concurrent use of multiple alkylating agents (see CLINICAL PHARMACOLOGY and Drug Interactions). A clear cause-and-effect relationship with busulfan has not been demonstrated. Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is indicated for early detection of hepatotoxicity. A reduced incidence of hepatic veno-occlusive disease and other regimen-related toxicities have been observed in patients treated with high-dose MYLERAN and cyclophosphamide when the first dose of cyclophosphamide has been delayed for >24 hours after the last dose of busulfan (see CLINICAL PHARMACOLOGY and Drug Interactions).
Fluid around the heart (cardiac tamponade) was reported in 2% in one series of patients with thalassemia who took busulfan and cyclophosphamide before a bone marrow transplant. It was often fatal. Belly pain and vomiting came first in most patients.
Heading
Cardiac tamponade
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
Cardiac tamponade has been reported in a small number of patients with thalassemia (2% in one series) who received busulfan and cyclophosphamide as the preparatory regimen for bone marrow transplantation. In this series, the cardiac tamponade was often fatal. Abdominal pain and vomiting preceded the tamponade in most patients.
Bone marrow suppression is the most consistent dose-related problem. Report fever, sore throat, signs of infection or any bleeding right away. Busulfan should never be taken without close medical supervision. Seizures have been reported, so caution is needed with a history of seizures or head injury.
Heading
General precautions (bone marrow suppression, seizures)
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
The most consistent, dose-related toxicity is bone marrow suppression. This may be manifest by anemia, leukopenia, thrombocytopenia, or any combination of these. It is imperative that patients be instructed to report promptly the development of fever, sore throat, signs of local infection, bleeding from any site, or symptoms suggestive of anemia. Any one of these findings may indicate busulfan toxicity; however, they may also indicate transformation of the disease to an acute “blastic” form. Since busulfan may have a delayed effect, it is important to withdraw the medication temporarily at the first sign of an abnormally large or exceptionally rapid fall in any of the formed elements of the blood. Patients should never be allowed to take the drug without close medical supervision. Seizures have been reported in patients receiving busulfan. As with any potentially epileptogenic drug, caution should be exercised when administering busulfan to patients with a history of seizure disorder, head trauma, or receiving other potentially epileptogenic drugs. Some investigators have used prophylactic anticonvulsant therapy in this setting.
Blood counts are checked weekly while taking busulfan.
Heading
Laboratory tests
Section
WARNINGS / PRECAUTIONS (Myleran label)
Source text (exact source wording)
It is recommended that evaluation of the hemoglobin or hematocrit, total white blood cell count and differential count, and quantitative platelet count be obtained weekly while the patient is on busulfan therapy. Busulfan should not be used where facilities for complete blood counts, including quantitative platelet counts, are not available at weekly (or more frequent) intervals.
Pregnancy and breastfeeding
Busulfan may cause fetal harm. There are no adequate and well-controlled studies in pregnant women, and women who could become pregnant should avoid becoming pregnant. It is not known whether busulfan passes into human milk. Because of its tumor-causing potential, a decision should be made whether to stop nursing or stop the drug. MedlinePlus says to use a reliable method of birth control and to call your doctor right away if you become pregnant.
Section
WARNINGS, Pregnancy; PRECAUTIONS, Lactation; MedlinePlus What special precautions should I follow?
Source
Label and MedlinePlus
Source text (exact source wording)
Pregnancy Busulfan may cause fetal harm when administered to a pregnant woman. Although there have been a number of cases reported where apparently normal children have been born after busulfan treatment during pregnancy, one case has been cited where a malformed baby was delivered by a mother treated with busulfan. During the pregnancy that resulted in the malformed infant, the mother received x-ray therapy early in the first trimester, mercaptopurine until the third month, then busulfan until delivery. In pregnant rats, busulfan produces sterility in both male and female offspring due to the absence of germinal cells in testes and ovaries. Germinal cell aplasia or sterility in offspring of mothers receiving busulfan during pregnancy has not been reported in humans. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Lactation It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown for busulfan in animal and human studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. // MedlinePlus: Busulfan may harm the fetus. Use a reliable method of birth control to prevent pregnancy. If you become pregnant while taking busulfan, call your doctor immediately.
Side effects
Common
The most frequent serious effect is dose-related bone marrow suppression, causing low white blood cells, low platelets and anemia. Skin darkening (hyperpigmentation) is the most common skin reaction and occurs in 5% to 10% of patients.
Section
ADVERSE REACTIONS, Hematological Effects; Dermatologic
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Hematological Effects: The most frequent, serious, toxic effect of busulfan is dose-related myelosuppression resulting in leukopenia, thrombocytopenia, and anemia. Myelosuppression is most frequently the result of a failure to discontinue dosage in the face of an undetected decrease in leukocyte or platelet counts. // Dermatologic: Hyperpigmentation is the most common adverse skin reaction and occurs in 5% to 10% of patients, particularly those with a dark complexion.
Less common
Other reported effects include hives, hair loss, dry skin, dry mouth, gynecomastia, cholestatic jaundice and cataracts (rare). Most are single case reports. MedlinePlus also lists nausea, diarrhea, loss of appetite or weight, constipation, mouth sores, headache, trouble sleeping, dizziness and swelling.
Section
ADVERSE REACTIONS, Miscellaneous, Ocular; MedlinePlus What side effects can this medication cause?
Source
Label and MedlinePlus (labeled in text)
Source text (exact source wording)
Miscellaneous: Other reported adverse reactions include: urticaria, erythema multiforme, erythema nodosum, alopecia, porphyria cutanea tarda, excessive dryness and fragility of the skin with anhidrosis, dryness of the oral mucous membranes and cheilosis, gynecomastia, cholestatic jaundice, and myasthenia gravis. Most of these are single case reports, and in many, a clear cause-and-effect relationship with busulfan has not been demonstrated. Seizures (see PRECAUTIONS: General) have been observed in patients receiving higher than recommended doses of busulfan. // Ocular: Busulfan is capable of inducing cataracts in rats and there have been several reports indicating that this is a rare complication in humans. // MedlinePlus (tell your doctor if severe): nausea, diarrhea, loss of appetite or weight, constipation, sores in the mouth and throat, dry mouth, headache, difficulty falling asleep or staying asleep, feeling unusually anxious or worried, dizziness, swelling of the face, arms, hands, feet, ankles or lower legs, chest pain, joint, muscle or back pain, skin rash, itching and dry skin, darkened skin, hair loss.
Serious
From the label: pulmonary fibrosis, aplastic anemia, hepatic veno-occlusive disease, a syndrome like adrenal insufficiency, cataracts, infection and sepsis, and seizures. MedlinePlus says to call your doctor right away for black tarry stools, red urine, unusual tiredness or weakness, trouble breathing, vision changes, vomiting, stomach pain or seizures.
Label
Section
ADVERSE REACTIONS; WARNINGS
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Pulmonary: Interstitial pulmonary fibrosis has been reported rarely, but it is a clinically significant adverse effect when observed and calls for immediate discontinuation of further administration of the drug. // Hematological Effects: Aplastic anemia (sometimes irreversible) has been reported rarely, often following long-term conventional doses and also high doses of MYLERAN. // Hepatic Effects: Hepatic veno-occlusive disease has been observed in patients receiving busulfan (see WARNINGS). // Metabolic: In a few cases, a clinical syndrome closely resembling adrenal insufficiency and characterized by weakness, severe fatigue, anorexia, weight loss, nausea and vomiting, and melanoderma has developed after prolonged busulfan therapy. // Observed During Clinical Practice: Blood and Lymphatic: Aplastic anemia. Eye: Cataracts, corneal thinning, lens changes. Hepatobiliary Tract and Pancreas: Centrilobular sinusoidal fibrosis, hepatic veno-occlusive disease, hepatocellular atrophy, hepatocellular necrosis, hyperbilirubinemia. Non-site Specific: Infection, mucositis, sepsis. Respiratory: Pneumonia. Skin: Rash.
Medlineplus
Section
What side effects can this medication cause?
Source
MedlinePlus Busulfan (a682248)
Source text (exact source wording)
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately: black, tarry stools red urine unusual tiredness or weakness difficulty breathing changes in vision vomiting stomach pain seizures. // Busulfan may cause ovarian failure and may stop girls from reaching puberty.
Led to discontinuation
Section
no discontinuation rate in the Myleran label
Interactions
Drugs
Busulfan can add to the bone marrow suppression caused by other drugs that do the same.
Name
Other myelosuppressive drugs
Section
PRECAUTIONS, Drug Interactions
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Busulfan may cause additive myelosuppression when used with other myelosuppressive drugs.
Long-term continuous use with thioguanine should be used with caution because liver problems and esophageal varices were seen in 12 of approximately 330 patients in one study.
Name
Thioguanine
Section
PRECAUTIONS, Drug Interactions
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
In one study, 12 of approximately 330 patients receiving continuous busulfan and thioguanine therapy for treatment of chronic myelogenous leukemia were found to have portal hypertension and esophageal varices associated with abnormal liver function tests. Subsequent liver biopsies were performed in 4 of these patients, all of which showed evidence of nodular regenerative hyperplasia. Duration of combination therapy prior to the appearance of esophageal varices ranged from 6 to 45 months. With the present analysis of the data, no cases of hepatotoxicity have appeared in the busulfan-alone arm of the study. Long-term continuous therapy with thioguanine and busulfan should be used with caution.
Itraconazole reduced busulfan clearance by up to 25% and may lead to toxic levels in some patients, so patients should be monitored for busulfan toxicity. Fluconazole had no effect on clearance.
Name
Itraconazole
Section
PRECAUTIONS, Drug Interactions; CLINICAL PHARMACOLOGY, Drug Interactions
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
The concomitant systemic administration of itraconazole to patients receiving high-dose MYLERAN may result in reduced busulfan clearance (see CLINICAL PHARMACOLOGY). Patients should be monitored for signs of busulfan toxicity when itraconazole is used concomitantly with MYLERAN. // CLINICAL PHARMACOLOGY: Itraconazole reduced busulfan clearance by up to 25% in patients receiving itraconazole compared to patients who did not receive itraconazole. Higher busulfan exposure due to concomitant itraconazole could lead to toxic plasma levels in some patients. Fluconazole had no effect on the clearance of busulfan.
With phenytoin pretreatment, clearance of both cyclophosphamide and busulfan rises, which may lower their levels. Busulfan clearance may be reduced by cyclophosphamide alone. Diazepam had no effect.
Name
Cyclophosphamide and phenytoin
Section
CLINICAL PHARMACOLOGY, Drug Interactions
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Patients treated with concomitant cyclophosphamide and busulfan with phenytoin pretreatment have increased cyclophosphamide and busulfan clearance, which may lead to decreased concentrations of both cyclophosphamide and busulfan. However, busulfan clearance may be reduced in the presence of cyclophosphamide alone, presumably due to competition for glutathione. Diazepam had no effect on the clearance of busulfan.
Busulfan lung toxicity may add to the effects of other cytotoxic drugs.
Name
Other cytotoxic agents (lung toxicity)
Section
PRECAUTIONS, Drug Interactions
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Busulfan-induced pulmonary toxicity may be additive to the effects produced by other cytotoxic agents.
MedlinePlus says acetaminophen may interact with busulfan and not to start it while taking busulfan without talking to your healthcare provider. The Myleran label text read does not mention acetaminophen.
Name
Acetaminophen (MedlinePlus only)
Section
What special precautions should I follow?
Source
MedlinePlus Busulfan (a682248)
Source text (exact source wording)
the following nonprescription products may interact with busulfan: acetaminophen(Tylenol). Be sure to let your doctor and pharmacist know that you are taking this medication before you start taking busulfan. Do not start this medication while taking busulfan without discussing with your healthcare provider.
Food and alcohol
The label says there are no data on how food affects busulfan.
Name
Food
Section
CLINICAL PHARMACOLOGY
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Currently, there are no available data on the effect of food on busulfan bioavailability.
Name
Alcohol
Section
not in cited sources
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Patient tips
Take it exactly as directed, once a day at about the same time. Get regular blood counts and report fever, unusual bleeding, trouble breathing, persistent cough, or congestion right away. Report weakness, unusual fatigue, weight loss, nausea or vomiting. Never take it without medical supervision, and do not stop it without talking to your doctor. Women who could become pregnant should avoid becoming pregnant.
Label patient information
Section
PRECAUTIONS, Information for Patients (the Myleran label has no separate Patient Information leaflet in the SPL text read)
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Source text (exact source wording)
Information for Patients: Patients beginning therapy with busulfan should be informed of the importance of having periodic blood counts and to immediately report any unusual fever or bleeding. Aside from the major toxicity of myelosuppression, patients should be instructed to report any difficulty in breathing, persistent cough, or congestion. They should be told that diffuse pulmonary fibrosis is an infrequent, but serious and potentially life-threatening complication of long-term busulfan therapy. Patients should be alerted to report any signs of abrupt weakness, unusual fatigue, anorexia, weight loss, nausea and vomiting, and melanoderma that could be associated with a syndrome resembling adrenal insufficiency. Patients should never be allowed to take the drug without medical supervision and they should be informed that other encountered toxicities to busulfan include infertility, amenorrhea, skin hyperpigmentation, drug hypersensitivity, dryness of the mucous membranes, and rarely, cataract formation. Women of childbearing potential should be advised to avoid becoming pregnant. The increased risk of a second malignancy should be explained to the patient.
Medlineplus
Section
MedlinePlus How should this medicine be used?
Source
MedlinePlus Busulfan (a682248)
Source text (exact source wording)
Busulfan comes as a tablet to take by mouth once a day. ... Take busulfan at around the same time every day. Follow the directions on your prescription label carefully ... Take busulfan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. // Do not stop taking busulfan without talking to your doctor. // Keep all appointments with your doctor and the laboratory.
Alternatives
Class source
Label DESCRIPTION: bifunctional alkylating agent; MedlinePlus: alkylating agents. openFDA pharm_class_epc: not queried.
Indication source
Label INDICATIONS: palliative treatment of chronic myelogenous leukemia
Frequently asked questions
Question
What is Myleran (busulfan) used for?
Answer
Myleran tablets are used for the palliative treatment of chronic myelogenous leukemia. MedlinePlus also says busulfan tablets are used with other drugs before a bone marrow transplant.
Source section
INDICATIONS AND USAGE; MedlinePlus Other uses
Source
Label and MedlinePlus
Question
Is there a generic busulfan tablet?
Answer
In the DailyMed search done for this record, the only busulfan tablet found was the brand Myleran. All other busulfan labels found were injections.
Source section
DailyMed search results
Source
DailyMed spls.json?drug_name=busulfan
Question
How is it taken?
Answer
By mouth. The usual adult dose to start is 4 to 8 mg total daily, and your doctor adjusts the dose from your blood counts. MedlinePlus says it is taken once a day at about the same time every day.
Source section
DOSAGE AND ADMINISTRATION; MedlinePlus How should this medicine be used?
Source
Label and MedlinePlus
Question
What if I miss a dose?
Answer
The Myleran label gives no missed-dose instructions. MedlinePlus says to take the missed dose as soon as you remember it unless it is almost time for the next dose, and not to take a double dose.
Source section
MedlinePlus What should I do if I forget a dose?
Source
MedlinePlus Busulfan (a682248)
Question
What are the most serious side effects?
Answer
The most frequent serious effect is bone marrow suppression, which lowers blood cell counts. A rare lung problem, pulmonary fibrosis, can also happen. Report fever, unusual bleeding, trouble breathing or a persistent cough right away.
Source section
WARNINGS; ADVERSE REACTIONS; Information for Patients
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Question
Does busulfan affect fertility or pregnancy?
Answer
Busulfan may cause fetal harm. Periods can stop in premenopausal women, and sterility has been reported in men. Women who could become pregnant should avoid becoming pregnant.
Source section
WARNINGS, Pregnancy; Ovarian suppression
Source
DailyMed label, MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC, set ID 2da33e5b-dcfb-4cdf-b163-50398e42f41c
Question
Does busulfan interact with other medicines?
Answer
Yes. The label names other drugs that suppress bone marrow, thioguanine, itraconazole, and phenytoin with cyclophosphamide. MedlinePlus also names acetaminophen. Tell your doctor and pharmacist about everything you take.
Source section
PRECAUTIONS, Drug Interactions; CLINICAL PHARMACOLOGY; MedlinePlus
Source
Label and MedlinePlus
Sources
- DailyMed label MYLERAN (busulfan) tablet, film coated, Waylis Therapeutics LLC
Set id: 2da33e5b-dcfb-4cdf-b163-50398e42f41c · Label effective or revised date: Label text shows 'Rev. 02/2023'; no 'Revised:' line found · Dailymed version date: SPL effectiveTime 2025-01-08; DailyMed list published_date Jan 10, 2025 · Fetched at: 2026-11-02 · Sections used: all - MedlinePlus Busulfan (oral)
Set id: n/a · Label effective or revised date: Last Revised - 06/15/2017 · Fetched at: 2026-11-02 · Sections used: all patient sections - DailyMed busulfan list
Fetched at: 2026-11-02 · Sections used: product identification - DailyMed BUSULFAN injection, Sagent Pharmaceuticals (injection_record only)
Set id: 086a715e-4958-4bb5-9ebd-86171e6b6203 · Label effective or revised date: Revised: November 2025 · Dailymed version date: SPL effectiveTime 2026-07-29; DailyMed list published_date Aug 07, 2026 · Fetched at: 2026-11-02 · Sections used: Boxed warning, 1, 4 only - DailyMed BUSULFEX injection, Otsuka (injection_record only)
Set id: 5cb9d285-1803-4a99-946a-d0b239b32df6 · Label effective or revised date: NOT FOUND (no Revised line found in label text read) · Dailymed version date: SPL effectiveTime 2026-10-14; DailyMed list published_date Oct 19, 2026 · Fetched at: 2026-11-02 · Sections used: Boxed warning, 1, 4 only - MedlinePlus Busulfan Injection
Fetched at: 2026-11-02 · Sections used: label not opened (URL only, found in search) - Drugs@FDA
Sections used: NOT FOUND (not searched successfully)
Information is taken from the cited sources and is for general reference only. It is not medical advice. Report side effects to FDA MedWatch at 1-800-FDA-1088. For a poison emergency call 1-800-222-1222. See prices for this drug