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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(byoo SUL fan)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Palliative treatment of chronic myelogenous leukemia (CML) (oral); conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation (I.V.) for CML
Use: Unlabeled
Conditioning regimen prior to hematopoietic stem cell transplant (HSCT) (oral); treatment of polycythemia vera and essential thrombocytosis
Pregnancy Risk Factor
D
Pregnancy Considerations
Animal studies have demonstrated teratogenic effects. There are no adequate and well-controlled studies in pregnant women. May cause fetal harm if administered during pregnancy. The solvent in I.V. busulfan, DMA, is also associated with teratogenic effects and may impair fertility. Women of childbearing potential should avoid pregnancy while receiving busulfan treatment.
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
Contraindications
Hypersensitivity to busulfan or any component of the formulation; oral busulfan is contraindicated in patients without a definitive diagnosis of CML
Warnings/Precautions
Boxed warnings:
• Bone marrow suppression: See “Concerns related to adverse effects” below.
• Experienced physician: See “Other warnings/precautions” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bone marrow suppression: [U.S. Boxed Warning]: Severe bone marrow suppression is common; reduce dose or discontinue oral busulfan for unusual suppression; may require bone marrow biopsy. May result in severe neutropenia, thrombocytopenia, anemia, bone marrow failure, and/or severe pancytopenia; pancytopenia may be prolonged (1 month up to 2 years) and may be reversible. Use with caution in patients with compromised bone marrow reserve (due to prior treatment or radiation therapy). Monitor closely for signs of infection (due to neutropenia) or bleeding (due to thrombocytopenia).
• Cardiovascular: Cardiac tamponade has been reported in children with thalassemia treated with high dose oral busulfan in combination with cyclophosphamide,
• Hepatic sinusoidal obstruction syndrome: High busulfan area under the concentration versus time curve (AUC) values (>1500 micromolar•minute) are associated with increased risk of hepatic sinusoidal obstruction syndrome (SOS; formerly called veno-occlusive disease [VOD]) due to conditioning for allogenic HSCT. Patients with a history of radiation therapy, prior chemotherapy (≥3 cycles), or prior stem cell transplantation are also at increased risk of hepatic SOS at recommended doses regimens. Oral busulfan doses above 16 mg/kg (based on IBW) and concurrent use with alkylating agents may also increase the risk for hepatic SOS. Monitor liver function tests periodically.
• Ovarian failure: Use has been associated with ovarian failure (including failure to achieve puberty) and amenorrhea.
• Pulmonary toxicity: Bronchopulmonary dysplasia with pulmonary fibrosis (“busulfan lung”) is associated with busulfan; onset is delayed with symptoms occurring at an average of 4 years (range: 4 months to 10 years) after treatment; may be fatal. Symptoms generally include a slow onset of cough, dyspnea and fever (low-grade), although acute symptomatic onset may also occur. Diminished diffusion capacity and decreased pulmonary compliance have been noted with pulmonary function testing. Differential diagnosis should rule out opportunistic pulmonary infection or leukemic pulmonary infiltrates; may require lung biopsy. Discontinue busulfan if toxicity develops. Pulmonary toxicity may be additive if administered with other cytotoxic agents also associated with pulmonary toxicity.
• Secondary malignancies: Tumors and acute leukemias have been reported following use. Chromosomal alterations may also occur.
• Tissue dysplasia: Cellular dysplasia in many organs has been observed (in addition to lung dysplasia); giant hyperchromatic nuclei have been noted in adrenal glands, liver, lymph nodes, pancreas, thyroid, and bone marrow. May obscure routine diagnostic cytologic exams (eg, cervical smear).
Disease-related concerns:
• Seizures: Seizures have been reported with busulfan; use with caution in patients predisposed to seizures, with a history of seizures or head trauma. When using as a conditioning regimen for transplant, initiate prophylactic anticonvulsant therapy (eg, phenytoin) prior to treatment.
Concurrent drug therapy issues:
• Anticonvulsants: Phenytoin increases busulfan clearance by ≥15%; busulfan kinetics and dosing recommendations for high-dose HSCT conditioning were studied with concomitant phenytoin. If alternate anticonvulsants are used, busulfan clearance may be decreased and dosing should be monitored accordingly.
Dosage form specific issues:
• Dimethylacetamide (DMA): The solvent in I.V. busulfan, DMA, may impair fertility. DMA may also be associated with hepatotoxicity, hallucinations, somnolence, lethargy, and confusion.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. For the I.V. formulation, should be experienced in management of hematopoietic stem cell transplantation and management of patients with severe pancytopenia. According to the manufacturer, oral busulfan should not be used until CML diagnosis has been established.
Adverse Reactions
I.V.:
>10%:
Cardiovascular: Tachycardia (44%), hypertension (36%; grades 3/4: 7%), edema (28% to 79%), thrombosis (33%), chest pain (26%), vasodilation (25%), hypotension (11%; grades 3/4: 3%)
Central nervous system: Insomnia (84%), fever (80%), anxiety (72% to 75%), headache (69%), chills (46%), pain (44%), dizziness (30%), depression (23%), confusion (11%)
Dermatologic: Rash (57%), pruritus (28%), alopecia (17%)
Endocrine & metabolic: Hypomagnesemia (77%), hyperglycemia (66% to 67%; grades 3/4: 15%), hypokalemia (64%), hypocalcemia (49%), hypophosphatemia (17%)
Gastrointestinal: Vomiting (43% to 100%), nausea (83% to 98%), mucositis/stomatitis (79% to 97%; grades 3/4: 26%), anorexia (85%), diarrhea (84%; grades 3/4: 5%), abdominal pain (72%), dyspepsia (44%), constipation (38%), xerostomia (26%), rectal disorder (25%), abdominal fullness (23%)
Hematologic: Myelosuppression (≤100%), neutropenia (100%; onset: 4 days; median recovery: 13 days [with G-CSF support]), thrombocytopenia (98%; median onset: 5-6 days), lymphopenia (children: 79%), anemia (69%)
Hepatic: Hyperbilirubinemia (49%; grades 3/4: 30%), ALT increased (31%; grades 3/4: 7%), hepatic sinusoidal obstruction syndrome (SOS; veno-occlusive disease) (adults: 8% to 12%; children: 21%), alkaline phosphatase increased (15%), jaundice (12%)
Local: Injection site inflammation (25%), injection site pain (15%)
Neuromuscular & skeletal: Weakness (51%), back pain (23%), myalgia (16%), arthralgia (13%)
Renal: Creatinine increased (21%), oliguria (15%)
Respiratory: Rhinitis (44%), lung disorder (34%), cough (28%), epistaxis (25%), dyspnea (25%), pneumonia (children: 21%), hiccup (18%), pharyngitis (18%)
Miscellaneous: Infection (51%; includes severe bacterial, viral [CMV], and fungal infections), allergic reaction (26%)
1% to 10%:
Cardiovascular: Arrhythmia (5%), cardiomegaly (5%), atrial fibrillation (2%), ECG abnormal (2%), heart block (2%), heart failure (grade 3/4: 2%), pericardial effusion (2%), tamponade (children with thalassemia: 2%), ventricular extrasystoles (2%), hypervolemia
Central nervous system: Lethargy (7%), hallucination (5%), agitation (2%), delirium (2%), encephalopathy (2%), seizure (2%), somnolence (2%), cerebral hemorrhage (1%)
Dermatologic: Vesicular rash (10%), vesiculobullous rash (10%), skin discoloration (8%), maculopapular rash (8%), acne (7%), exfoliative dermatitis (5%), erythema nodosum (2%)
Endocrine & metabolic: Hyponatremia (2%)
Gastrointestinal: Ileus (8%), weight gain (8%), esophagitis (grade 3: 2%), hematemesis (2%), pancreatitis (2%)
Hematologic: Prothrombin time increased (2%)
Hepatic: Hepatomegaly (6%)
Renal: Hematuria (8%), dysuria (7%), hemorrhagic cystitis (grade 3/4: 7%), BUN increased (3%; grades 3/4: 2%)
Respiratory: Asthma (8%), alveolar hemorrhage (5%), hyperventilation (5%), hemoptysis (3%), pleural effusion (3%), sinusitis (3%), atelectasis (2%), hypoxia (2%)
Oral: Frequency not defined:
Dermatologic: Hyperpigmentation of skin (5% to 10%), rash
Endocrine & metabolic: Amenorrhea, ovarian suppression
Gastrointestinal: Xerostomia
Hematologic: Myelosuppression (anemia, leukopenia, thrombocytopenia)
I.V. and/or Oral: Infrequent, postmarketing, and/or case reports: Acute leukemias, adrenal insufficiency, alopecia (permanent), aplastic anemia (may be irreversible), azoospermia, bronchopulmonary dysplasia, capillary leak syndrome, cataracts (rare), cheilosis, cholestatic jaundice, corneal thinning, dry skin, endocardial fibrosis, erythema multiforme, esophageal varices, gynecomastia, hepatic dysfunction, hepatocellular atrophy, hyperuricemia, hyperuricosuria, interstitial pulmonary fibrosis, malignant tumors, myasthenia gravis, neutropenic fever, ocular (lens) changes, ovarian failure, pancytopenia, porphyria cutanea tarda, pulmonary fibrosis, radiation myelopathy, radiation recall (skin rash), sepsis, sterility, testicular atrophy, thrombotic microangiopathy (TMA), tumor lysis syndrome, urticaria
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Acetaminophen: May increase the serum concentration of Busulfan. Risk C: Monitor therapy
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Busulfan. Risk C: Monitor therapy
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Fosphenytoin: May decrease the serum concentration of Busulfan. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
MetroNIDAZOLE: May increase the serum concentration of Busulfan. Risk D: Consider therapy modification
MetroNIDAZOLE (Systemic): May increase the serum concentration of Busulfan. Management: The toxic effects of busulfan may be greatly increased with concomitant use of metronidazole. This combination should probably be avoided when possible. If these agents must be used together, increased monitoring for busulfan toxicity is recommended. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Phenytoin: May decrease the serum concentration of Busulfan. Risk C: Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Antineoplastic Agents may enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol due to GI irritation.
Food: No clear or firm data on the effect of food on busulfan bioavailability.
Herb/Nutraceutical: Avoid St John's wort (may decrease busulfan levels).
Storage
Injection: Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F). Solutions diluted in sodium chloride (NS) injection or dextrose 5% in water (D5W) for infusion are stable for up to 8 hours at room temperature (25°C [77°F]); the infusion must also be completed within that 8-hour timeframe. Dilution of busulfan injection in NS is stable for up to 12 hours at refrigeration (2°C to 8°C); the infusion must be completed within that 12-hour timeframe.
Tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Reconstitution
Injection: Dilute NS or D5W. The dilution volume should be ten times the volume of busulfan injection, ensuring that the final concentration of busulfan is 0.5 mg/mL. Always add busulfan to the diluent, and not the diluent to the busulfan. Mix with several inversions. Do not use polycarbonate syringes or filters for preparation or administration.
Compatibility
Variable stability (consult detailed reference) in D5W, NS.
Mechanism of Action
Busulfan is an alkylating agent which reacts with the N-7 position of guanosine and interferes with DNA replication and transcription of RNA. Busulfan has a more marked effect on myeloid cells than on lymphoid cells and is also very toxic to hematopoietic stem cells. Busulfan exhibits little immunosuppressive activity. Interferes with the normal function of DNA by alkylation and cross-linking the strands of DNA.
Pharmacodynamics/Kinetics
Absorption: Rapid and complete
Distribution: Vd: ~1 L/kg; distributes into CSF with levels equal to plasma
Protein binding: 32% to plasma proteins and 47% to red blood cells
Metabolism: Extensively hepatic (may increase with multiple doses); glutathione conjugation followed by oxidation
Bioavailability: Oral: Children ≥13 years and adults: 80% ± 20%; Children 1.5-6 years: 68% ± 31%
Half-life elimination: 2-3 hours
Time to peak, serum: Oral: ~1 hour; I.V.: Within 5 minutes
Excretion: Urine (25% to 60% predominantly as metabolites; <2% as unchanged drug)
Dosage
Note: Premedicate with prophylactic anticonvulsant therapy (eg, phenytoin) prior to high-dose busulfan treatment. Prophylactic antiemetics may be necessary for high-dose (HSCT) regimens.
Children:
CML, palliation (manufacturer's labeling): Oral:
Remission induction: 60 mcg/kg/day or 1.8 mg/m2/day; titrate dose (or withhold) to maintain leukocyte counts ≥15,000/mm3 (doses >4 mg/day should be reserved for patients with the most compelling symptoms)
Maintenance: When leukocyte count ≥50,000/mm3: Resume induction dose or (if remission <3 months) 1-3 mg/day (to control hematologic status and prevent relapse)
HSCT conditioning regimen:
I.V.:
≤12 kg: 1.1 mg/kg/dose (actual body weight) every 6 hours for 16 doses
>12 kg: 0.8 mg/kg/dose (actual body weight) every 6 hours for 16 doses
Adjust dose to desired AUC (1125 micromolar•minute) using the following formula:
Adjusted dose (mg) = Actual dose (mg) x [target AUC (micromolar•minute) / actual AUC (micromolar•minute)]
Reduced intensity conditioning regimen (unlabeled dosing): 0.8 mg/kg/dose for 1 dose 7-10 days prior to transplant, followed by ~0.8 mg/kg/dose (busulfan kinetics calculated after initial dose) every 6 hours for 7 doses beginning 3-6 days prior to transplant (in combination with fludarabine and antithymocyte globulin) (Pulsipher, 2009)
Oral (unlabeled use): 1 mg/kg/dose every 6 hours for 16 doses beginning 9 days prior to transplant (in combination with cyclophosphamide) (Cassileth, 1998)
Adults:
CML, palliation (manufacturer's labeling): Oral:
Remission induction: 60 mcg/kg/day or 1.8 mg/m2/day; usual range: 4-8 mg/day; titrate dose (or withhold) to maintain leukocyte counts ≥15,000/mm3 (doses >4 mg/day should be reserved for patients with the most compelling symptoms)
Maintenance: When leukocyte count ≥50,000/mm3: Resume induction dose or (if remission <3 months) 1-3 mg/day (to control hematologic status and prevent relapse)
HSCT conditioning regimen:
I.V.:
0.8 mg/kg every 6 hours for 4 days (a total of 16 doses); Note: Use ideal body weight or actual body weight, (whichever is lower) for dosing. For obese or severely-obese patients, use of an adjusted body weight [IBW + 0.25 x (actual – IBW)] is recommended.
Reduced intensity conditioning regimen (unlabeled dosing): 0.8 mg/kg/day for 4 days starting 5 days prior to transplant (in combinations with fludarabine) (Ho, 2009)
Oral (unlabeled use): 1 mg/kg/dose every 6 hours for 16 doses (in combination with cyclophosphamide) (Socié, 2001) or 1 mg/kg/dose every 6 hours for 16 doses beginning 9 days prior to transplant (in combination with cyclophosphamide) (Cassileth, 1993) or 0.44 mg/kg/dose every 6 hours for 16 doses (in combination with cyclophosphamide) (Anderson, 1996) or 1 mg/kg/dose every 6 hours for 16 doses beginning 6 days prior to transplant (in combination with melphalan) (Fermand, 2005)
Polycythemia vera and essential thrombocythemia (unlabeled uses): Oral: 2-4 mg/day (Fabris, 2009; Tefferi, 2011)
Dosing adjustment in renal impairment:
I.V.: No dosage adjustment provided in the manufacturer's labeling (has not been studied).
Oral: No dosage adjustment provided in the manufacturer's labeling (elimination appears to be independent of renal function); however, some clinicians suggest adjustment is not necessary (Aronoff, 2007).
Dosing adjustment in hepatic impairment:
I.V.: No dosage adjustment provided in the manufacturer's labeling (has not been studied).
Oral: No dosage adjustment provided in the manufacturer's labeling.
Administration: Oral
HSCT only: To facilitate ingestion of high oral doses, may insert multiple tablets into gelatin capsules.
Administration: I.V.
Intravenous busulfan should be infused over 2 hours via central line. Flush line before and after each infusion with 5 mL D5W or NS. Do not use polycarbonate syringes or filters for preparation or administration
Monitoring Parameters
CBC with differential and platelet count (weekly for palliative treatment; daily until engraftment for HSCT); liver function tests (evaluate transaminases, alkaline phosphatase, and bilirubin daily for at least 28 days post transplant). If conducting therapeutic drug monitoring for AUC calculations in HSCT, monitor blood samples at appropriate collections times (record collection times).
Patient Education
Maintain adequate nutrition and hydration, unless instructed to restrict fluid intake. Avoid excess alcohol and acidic or spicy foods (may increase gastrointestinal irritation). You will be more susceptible to infection. May cause dizziness, insomnia, or confusion; mouth sores; loss of hair or darkening of skin color (reversible when medication is discontinued); nausea, vomiting, or loss of appetite; constipation; diarrhea (consult prescriber if severe or persistent); amenorrhea; sterility; or skin rash. Report palpitations or chest pain, weight gain, CNS changes (anxiety, confusion, depression), unusual cough or difficulty breathing, numbness or tingling of extremities, unusual bruising or bleeding, or pain or changes in urination.
Geriatric Considerations
Toxicity is increased in the elderly. Start with lowest recommended adult doses. Signs of infection, such as fever and rise in WBCs, may not occur. Lethargy and confusion may be more prominent signs of infection. Patients should report any development of persistent cough, dyspnea, and fever.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), mucositis/stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
May cause severe pancytopenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Identify any history of seizures, recent myelosuppressive therapy or radiation treatment, and pregnancy status prior to therapy. Dosing for obese patients should be based on adjusted ideal body weight. HSCT: Phenytoin or clonazepam may be ordered prophylactically during and for at least 48 hours following completion of busulfan to reduce risk of seizures if patient is predisposed to seizures. Assess CBC with differential, platelet count, and LFTs. Monitor for adverse pulmonary effects (pulmonary fibrosis or toxicity; may be delayed 4 months to 10 years) or hematologic effects (pancytopenia, leukopenia, thrombocytopenia, anemia, and bone marrow suppression) during therapy and for several months following therapy.
Oncology: Emetic Potential
Oral ≥4 mg/day and I.V.: Moderate (30% to 90%)
Oral <4 mg/day: Very low (<10%)
Oncology: Vesicant
May be an irritant
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
Busulfex®: 6 mg/mL (10 mL) [contains N,N-dimethylacetamide (DMA), polyethylene glycol 400]
Tablet, oral:
Myleran®: 2 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Myleran)
2 mg (60): $267.79
Extemporaneously Prepared
Hazardous agent: Use appropriate precautions for handling and disposal.
A 2 mg/mL oral suspension can be prepared in a vertical flow hood with tablets and simple syrup. Crush one-hundred-twenty 2 mg tablets in a mortar and reduce to a fine powder. Add small portions of simple syrup and mix to a uniform paste; mix while adding the simple syrup in incremental proportions to almost 120 mL; transfer to a graduated cylinder, rinse mortar and pestle with simple syrup, and add quantity of vehicle sufficient to make 120 mL. Transfer contents of the graduated cylinder into an amber prescription bottle. Label “shake well”, “refrigerate”, and “caution chemotherapy”. Stable for 30 days.
Allen LV, "Busulfan Oral Suspension," US Pharm, 1990, 15:94-5.
References
Anderson JE, Appelbaum FR, Schoch G, et al, “Allogeneic Marrow Transplantation for Myelodysplastic Syndrome With Advanced Disease Morphology: A Phase II Study of Busulfan, Cyclophosphamide, and Total Body-Irradiation and Analysis of Prognostic Factors,” J Clin Oncol, 1996, 14(1):220-6.
Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007, p 97, 169.
Booth BP, Rahman A, Dagher R, et al, “Population Pharmacokinetic-Based Dosing of Intravenous Busulfan in Pediatric Patients,” J Clin Pharmacol, 2007, 47(1):101-11.
Cassileth PA, Andersen J, Lazarus HM, et al, “Autologous Bone Marrow Transplant in Acute Myeloid Leukemia in First Remission,” J Clin Oncol, 1993, 11(2):314-9.
Cassileth PA, Harrington DP, Appelbaum FR, et al, “Chemotherapy Compared With Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission,” N Engl J Med, 1998, 339(23):1649-56.
Fabris F and Randi ML, “Essential Thrombocythemia: Past and Present,” Intern Emerg Med, 2009, 4(5):381-8.
Fermand JP, Katsahian S, Divine M, et al, “High-Dose Therapy and Autologous Blood Stem-Cell Transplantation Compared With Conventional Treatment in Myeloma Patients Aged 55 to 65 years: Long-Term Results of a Randomized Control Trial From the Group Myelome-Autogreffe,” J Clin Oncol, 2005, 23(36):9227-33.
Ho VT, Aldridge J, Kim HT, et al, Comparison of Tacrolimus and Sirolimus (Tac/Sir) Versus Tacrolimus, Sirolimus, and Mini-Methotrexate (Tac/Sir/MTX) as Acute Graft-Versus-Host Disease Prophylaxis After Reduced-Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation,” Biol Blood Marrow Transplant, 2009, 15(7):844-50.
Pulsipher MA, Boucher KM, Wall D, et al, “Reduced-Intensity Allogeneic Transplantation in Pediatric Patients Ineligible for Myeloablative Therapy: Results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313,” Blood, 2009, 114(7):1429-36.
Radich JP, Gooley T, Bensinger W, et al, “HLA-Matched Related Hematopoietic Cell Transplantation for Chronic-Phase CML Using a Targeted Busulfan and Cyclophosphamide Preparative Regimen,” Blood, 2003, 102(1):31-5.
Regazzi MB, Locatelli F, Buggia I, et al, “Disposition of High-Dose Busulfan in Pediatric Patients Undergoing Bone Marrow Transplantation,” Clin Pharmacol Ther, 1993, 54(1):45-52.
Seddon BM, Cassoni AM, Galloway MJ, et al, “Fatal Radiation Myelopathy After High-Dose Busulfan and Melphalan Chemotherapy and Radiotherapy for Ewing's Sarcoma: A Review of the Literature and Implications for Practice,” Clin Oncol (R Coll Radiol), 2005, 17(5):385-90.
Shaw PJ, Nath C, Berry A, et al, “Busulphan Given as Four Single Daily Doses of 150 mg/m2 Is Safe and Effective in Children of All Ages,” Bone Marrow Transplant, 2004, 34(3):197-205.
Socié G, Clift RA, Blaise D, et al, “Busulfan Plus Cyclophosphamide Compared With Total-Body Irradiation Plus Cyclophosphamide Before Marrow Transplantation for Myeloid Leukemia: Long-Term Follow-Up of 4 Randomized Studies,” Blood, 2001, 98(13):3569-74.
Tefferi A, “Annual Clinical Updates in Hematological Malignancies: A Continuing Medical Education Series: Polycythemia Vera and Essential Thrombocythemia: 2011 Update on Diagnosis, Risk-Stratification, and Management,” Am J Hematol, 2011, 86(3):292-301.
Tosti A, Piraccini BM, Vincenzi C, et al, “Permanent Alopecia After Busulfan Chemotherapy,” Br J Dermatol, 2005, 152(5):1056-8.
Vassal G, Gouyette A, Hartmann O, et al, “Pharmacokinetics of High-Dose Busulfan in Children,” Cancer Chemother Pharmacol, 1989, 24(6):386-90.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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