Busulfan (injection): Difference between revisions
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{{DrugProjectFormSinglePage | |||
|authorTag={{GP}} | |||
|genericName=Busulfan | |||
|aOrAn=an | |||
|drugClass=alkylating agent | |||
|indicationType=treatment | |||
|indication=chronic myelogenous leukemia | |||
|hasBlackBoxWarning=Yes | |||
|blackBoxWarningTitle=WARNING | |||
|blackBoxWarningBody=Busulfan is a potent cytotoxic drug that causes profound myelosuppression at the recommended dosage. It should be administered under the supervision of a qualified physician who is experienced in allogeneic hematopoietic stem cell transplantation, the use of cancer chemotherapeutic drugs and the management of patients with severe pancytopenia. Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available. | |||
|fdaLIADAdult=Busulfan is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. | |||
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Busulfan in adult patients. | |||
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Busulfan in adult patients. | |||
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Busulfan in pediatric patients. | |||
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Busulfan in pediatric patients. | |||
|contraindications=Busulfan is contraindicated in patients with a history of hypersensitivity to any of its components. | |||
|mechAction=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. This produces reactive carbonium ions that can alkylate DNA. DNA damage is thought to be responsible for much of the cytotoxicity of busulfan. | |||
|structure=Busulfan is known chemically as 1,4-butanediol dimethanesulfonate and has the following structural formula: | |||
CH3SO2O(CH2)4OSO2CH3 | |||
|PK=The pharmacokinetics of BUSULFEX were studied in 59 patients participating in a prospective trial of a BUSULFEX-cyclophosphamide preparatory regimen prior to allogeneic hematopoietic progenitor stem cell transplantation. Patients received 0.8 mg/kg BUSULFEX every six hours, for a total of 16 doses over four days. Fifty-five of fifty-nine patients (93%) administered BUSULFEX maintained AUC values below the target value (<1500 µM∙min). | |||
[[File:Busulfan Steady State Pharmacokinetic Parameters.png|thumb|none|500px]] | |||
Busulfan pharmacokinetics showed consistency between dose 9 and dose 13 as demonstrated by reproducibility of steady state Cmax and a low coefficient of variation for this parameter. | |||
In a pharmacokinetic study of BUSULFEX in 24 pediatric patients, the population pharmacokinetic (PPK) estimates of BUSULFEX for clearance (CL) and volume of distribution (V) were determined. For actual body weight, PPK estimates of CL and V were 4.04 L/hr/20 kg (3.37 mL/min/kg; interpatient variability 23%); and 12.8 L/20 kg (0.64 L/kg; interpatient variability 11%). | |||
=====Distribution, Metabolism, Excretion===== | |||
Studies of distribution, metabolism, and elimination of BUSULFEX have not been done; however, the literature on oral busulfan is relevant. Additionally, for modulating effects on pharmacodynamic parameters see DRUG INTERACTIONS. | |||
======Distribution====== | |||
Busulfan achieves concentrations in the cerebrospinal fluid approximately equal to those in plasma. Irreversible binding to plasma elements, primarily albumin, has been estimated to be 32.4±2.2% which is consistent with the reactive electrophilic properties of busulfan. | |||
======Metabolism====== | |||
Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis. This conjugate undergoes further extensive oxidative metabolism in the liver. | |||
======Excretion====== | |||
Following administration of 14C‑labeled busulfan to humans, approximately 30% of the radioactivity was excreted into the urine over 48 hours; negligible amounts were recovered in feces. The incomplete recovery of radioactivity may be due to the formation of long-lived metabolites or due to nonspecific alkylation of macromolecules. | |||
|clinicalStudies=Documentation of the safety and efficacy of busulfan as a component of a conditioning regimen prior to allogeneic hematopoietic progenitor cell reconstitution is derived from two sources: i) analysis of a prospective clinical trial of BUSULFEX that involved 61 patients diagnosed with various hematologic malignancies, and ii) the published reports of randomized, controlled trials that employed high-dose oral busulfan as a component of a conditioning regimen for transplantation, which were identified in a literature review of five established commercial databases. | |||
The prospective trial was a single-arm, open-label study in 61 patients who received BUSULFEX as part of a conditioning regimen for allogeneic hematopoietic stem cell transplantation. The study included patients with acute leukemia past first remission (first or subsequent relapse), with high-risk first remission, or with induction failure; chronic myelogenous leukemia (CML) in chronic phase, accelerated phase, or blast crisis; primary refractory or resistant relapsed Hodgkin's disease or non-Hodgkin's lymphoma; and myelodysplastic syndrome. Forty-eight percent of patients (29/61) were heavily pretreated, defined as having at least one of the following: prior radiation, ≥3 prior chemotherapeutic regimens, or prior hematopoietic stem cell transplant. Seventy-five percent of patients (46/61) were transplanted with active disease. | |||
Patients received 16 BUSULFEX doses of 0.8 mg/kg every 6 hours as a two‑hour infusion for 4 days, followed by cyclophosphamide 60 mg/kg once per day for two days (BuCy2 regimen). All patients received 100% of their scheduled BUSULFEX regimen. No dose adjustments were made. After one rest day, allogeneic hematopoietic progenitor cells were infused. The efficacy parameters in this study were myeloablation (defined as one or more of the following: absolute neutrophil count [ANC] less than 0.5×109/L, absolute lymphocyte count [ALC] less than 0.1×109/L, thrombocytopenia defined as a platelet count less than 20,000/mm3 or a platelet transfusion requirement) and engraftment (ANC ≥0.5×109/L). | |||
All patients (61/61) experienced myeloablation. The median time to neutropenia was 4 days. All evaluable patients (60/60) engrafted at a median of 13 days post-transplant (range 9 to 29 days); one patient was considered non-evaluable because he died of a fungal pneumonia 20 days after BMT and before engraftment occurred. All but 13 of the patients were treated with prophylactic G-CSF. Evidence of donor cell engraftment and chimerism was documented in all patients who had a chromosomal sex marker or leukemic marker (43/43), and no patient with chimeric evidence of allogeneic engraftment suffered a later loss of the allogeneic graft. There were no reports of graft failure in the overall study population. The median number of platelet transfusions per patient was 6, and the median number of red blood cell transfusions per patient was 4. | |||
Twenty-three patients (38%) relapsed at a median of 183 days post-transplant (range 36 to 406 days). Sixty-two percent of patients (38/61) were free from disease with a median follow-up of 269 days post-transplant (range 20 to 583 days). Forty-three patients (70%) were alive with a median follow up of 288 days post-transplant (range 51 to 583 days). There were two deaths before BMT Day +28 and six additional patients died by BMT Day +100. Ten patients (16%) died after BMT Day +100, at a median of 199 days post-transplant (range 113 to 275 days). | |||
=====Oral Busulfan Literature Review===== | |||
Four publications of randomized, controlled trials that evaluated a high-dose oral busulfan-containing conditioning regimen (busulfan 4 mg/kg/d ×4 days + cyclophosphamide 60 mg/kg/d ×2 days) for allogeneic transplantation in the setting of CML were identified. Two of the studies (Clift and Devergie) had populations confined to CML in chronic phase that were randomized between conditioning with busulfan/cyclophosphamide (BU/CY) and cyclophosphamide/total body irradiation (CY/TBI). A total of 138 patients were treated with BU/CY in these studies. The populations of the two remaining studies (Ringden and Blume) included patients with CML, acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML). In the Nordic BMT Group study published by Ringden, et al., 57 patients had CML, and of those, 30 were treated with BU/CY. Patients with CML in chronic phase, accelerated phase, and blast crisis were eligible for this study. The participants with CML (34/122 patients) in a SWOG study published by Blume, et al., had disease beyond first chronic phase. Twenty of those CML patients were treated with BU/CY, and the TBI comparator arm utilized etoposide instead of cyclophosphamide. | |||
[[File:Busulfan Summary of efficacy analyses from the randomized, controlled trials utilizing a high dose oral busulfan-containing conditioning regimen identified in a literature review.png|thumb|none|600px]] | |||
|alcohol=Alcohol-Busulfan interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. | |||
}} | |||
{{PillImage | |||
|fileName=MYLERAN_NDC_763880713.jpg | |||
|drugName=MYLERAN | |||
|NDC=763880713 | |||
|drugAuthor=Aspen Global Inc. | |||
|ingredients=BUSULFAN[BUSULFAN] | |||
|pillImprint=GX;EF3;M | |||
|dosageValue=2 | |||
|dosageUnit=mg | |||
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|pillScore=1 | |||
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{{PillImage | |||
|fileName=MYLERAN_NDC_01730713.jpg | |||
|drugName=MYLERAN | |||
|NDC=01730713 | |||
|drugAuthor=GlaxoSmithKline LLC | |||
|ingredients=BUSULFAN[BUSULFAN] | |||
|pillImprint=GX;EF3;M | |||
|dosageValue=2 | |||
|dosageUnit=mg | |||
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|pillScore=1 | |||
}} | |||
{{Drugbox| | {{Drugbox| | ||
|IUPAC_name = 1,4-bis(methylsulfonyloxy)butane | |IUPAC_name = 1,4-bis(methylsulfonyloxy)butane | ||
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===Pill Images=== | ===Pill Images=== | ||
{{TempDrugImages}} | {{TempDrugImages}} | ||
==Toxicity and side effects== | ==Toxicity and side effects== | ||
Revision as of 17:51, 29 January 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]
Disclaimer
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Black Box Warning
|
WARNING
See full prescribing information for complete Boxed Warning.
Busulfan is a potent cytotoxic drug that causes profound myelosuppression at the recommended dosage. It should be administered under the supervision of a qualified physician who is experienced in allogeneic hematopoietic stem cell transplantation, the use of cancer chemotherapeutic drugs and the management of patients with severe pancytopenia. Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available.
|
Overview
Busulfan (injection) is an alkylating agent that is FDA approved for the treatment of chronic myelogenous leukemia. There is a Black Box Warning for this drug as shown here. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Busulfan is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Busulfan in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Busulfan in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Busulfan (injection) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Busulfan in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Busulfan in pediatric patients.
Contraindications
Busulfan is contraindicated in patients with a history of hypersensitivity to any of its components.
Warnings
|
WARNING
See full prescribing information for complete Boxed Warning.
Busulfan is a potent cytotoxic drug that causes profound myelosuppression at the recommended dosage. It should be administered under the supervision of a qualified physician who is experienced in allogeneic hematopoietic stem cell transplantation, the use of cancer chemotherapeutic drugs and the management of patients with severe pancytopenia. Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available.
|
There is limited information regarding Busulfan (injection) Warnings' in the drug label.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Busulfan (injection) Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Busulfan (injection) Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Busulfan (injection) Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Busulfan (injection) in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Busulfan (injection) in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Busulfan (injection) during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Busulfan (injection) in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Busulfan (injection) in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Busulfan (injection) in geriatric settings.
Gender
There is no FDA guidance on the use of Busulfan (injection) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Busulfan (injection) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Busulfan (injection) in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Busulfan (injection) in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Busulfan (injection) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Busulfan (injection) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Busulfan (injection) Administration in the drug label.
Monitoring
There is limited information regarding Busulfan (injection) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Busulfan (injection) and IV administrations.
Overdosage
There is limited information regarding Busulfan (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Busulfan (injection) Pharmacology in the drug label.
Mechanism of Action
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. This produces reactive carbonium ions that can alkylate DNA. DNA damage is thought to be responsible for much of the cytotoxicity of busulfan.
Structure
Busulfan is known chemically as 1,4-butanediol dimethanesulfonate and has the following structural formula: CH3SO2O(CH2)4OSO2CH3
Pharmacodynamics
There is limited information regarding Busulfan (injection) Pharmacodynamics in the drug label.
Pharmacokinetics
The pharmacokinetics of BUSULFEX were studied in 59 patients participating in a prospective trial of a BUSULFEX-cyclophosphamide preparatory regimen prior to allogeneic hematopoietic progenitor stem cell transplantation. Patients received 0.8 mg/kg BUSULFEX every six hours, for a total of 16 doses over four days. Fifty-five of fifty-nine patients (93%) administered BUSULFEX maintained AUC values below the target value (<1500 µM∙min).
Busulfan pharmacokinetics showed consistency between dose 9 and dose 13 as demonstrated by reproducibility of steady state Cmax and a low coefficient of variation for this parameter.
In a pharmacokinetic study of BUSULFEX in 24 pediatric patients, the population pharmacokinetic (PPK) estimates of BUSULFEX for clearance (CL) and volume of distribution (V) were determined. For actual body weight, PPK estimates of CL and V were 4.04 L/hr/20 kg (3.37 mL/min/kg; interpatient variability 23%); and 12.8 L/20 kg (0.64 L/kg; interpatient variability 11%).
Distribution, Metabolism, Excretion
Studies of distribution, metabolism, and elimination of BUSULFEX have not been done; however, the literature on oral busulfan is relevant. Additionally, for modulating effects on pharmacodynamic parameters see DRUG INTERACTIONS.
Distribution
Busulfan achieves concentrations in the cerebrospinal fluid approximately equal to those in plasma. Irreversible binding to plasma elements, primarily albumin, has been estimated to be 32.4±2.2% which is consistent with the reactive electrophilic properties of busulfan.
Metabolism
Busulfan is predominantly metabolized by conjugation with glutathione, both spontaneously and by glutathione S-transferase (GST) catalysis. This conjugate undergoes further extensive oxidative metabolism in the liver.
Excretion
Following administration of 14C‑labeled busulfan to humans, approximately 30% of the radioactivity was excreted into the urine over 48 hours; negligible amounts were recovered in feces. The incomplete recovery of radioactivity may be due to the formation of long-lived metabolites or due to nonspecific alkylation of macromolecules.
Nonclinical Toxicology
There is limited information regarding Busulfan (injection) Nonclinical Toxicology in the drug label.
Clinical Studies
Documentation of the safety and efficacy of busulfan as a component of a conditioning regimen prior to allogeneic hematopoietic progenitor cell reconstitution is derived from two sources: i) analysis of a prospective clinical trial of BUSULFEX that involved 61 patients diagnosed with various hematologic malignancies, and ii) the published reports of randomized, controlled trials that employed high-dose oral busulfan as a component of a conditioning regimen for transplantation, which were identified in a literature review of five established commercial databases.
The prospective trial was a single-arm, open-label study in 61 patients who received BUSULFEX as part of a conditioning regimen for allogeneic hematopoietic stem cell transplantation. The study included patients with acute leukemia past first remission (first or subsequent relapse), with high-risk first remission, or with induction failure; chronic myelogenous leukemia (CML) in chronic phase, accelerated phase, or blast crisis; primary refractory or resistant relapsed Hodgkin's disease or non-Hodgkin's lymphoma; and myelodysplastic syndrome. Forty-eight percent of patients (29/61) were heavily pretreated, defined as having at least one of the following: prior radiation, ≥3 prior chemotherapeutic regimens, or prior hematopoietic stem cell transplant. Seventy-five percent of patients (46/61) were transplanted with active disease.
Patients received 16 BUSULFEX doses of 0.8 mg/kg every 6 hours as a two‑hour infusion for 4 days, followed by cyclophosphamide 60 mg/kg once per day for two days (BuCy2 regimen). All patients received 100% of their scheduled BUSULFEX regimen. No dose adjustments were made. After one rest day, allogeneic hematopoietic progenitor cells were infused. The efficacy parameters in this study were myeloablation (defined as one or more of the following: absolute neutrophil count [ANC] less than 0.5×109/L, absolute lymphocyte count [ALC] less than 0.1×109/L, thrombocytopenia defined as a platelet count less than 20,000/mm3 or a platelet transfusion requirement) and engraftment (ANC ≥0.5×109/L).
All patients (61/61) experienced myeloablation. The median time to neutropenia was 4 days. All evaluable patients (60/60) engrafted at a median of 13 days post-transplant (range 9 to 29 days); one patient was considered non-evaluable because he died of a fungal pneumonia 20 days after BMT and before engraftment occurred. All but 13 of the patients were treated with prophylactic G-CSF. Evidence of donor cell engraftment and chimerism was documented in all patients who had a chromosomal sex marker or leukemic marker (43/43), and no patient with chimeric evidence of allogeneic engraftment suffered a later loss of the allogeneic graft. There were no reports of graft failure in the overall study population. The median number of platelet transfusions per patient was 6, and the median number of red blood cell transfusions per patient was 4.
Twenty-three patients (38%) relapsed at a median of 183 days post-transplant (range 36 to 406 days). Sixty-two percent of patients (38/61) were free from disease with a median follow-up of 269 days post-transplant (range 20 to 583 days). Forty-three patients (70%) were alive with a median follow up of 288 days post-transplant (range 51 to 583 days). There were two deaths before BMT Day +28 and six additional patients died by BMT Day +100. Ten patients (16%) died after BMT Day +100, at a median of 199 days post-transplant (range 113 to 275 days).
Oral Busulfan Literature Review
Four publications of randomized, controlled trials that evaluated a high-dose oral busulfan-containing conditioning regimen (busulfan 4 mg/kg/d ×4 days + cyclophosphamide 60 mg/kg/d ×2 days) for allogeneic transplantation in the setting of CML were identified. Two of the studies (Clift and Devergie) had populations confined to CML in chronic phase that were randomized between conditioning with busulfan/cyclophosphamide (BU/CY) and cyclophosphamide/total body irradiation (CY/TBI). A total of 138 patients were treated with BU/CY in these studies. The populations of the two remaining studies (Ringden and Blume) included patients with CML, acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML). In the Nordic BMT Group study published by Ringden, et al., 57 patients had CML, and of those, 30 were treated with BU/CY. Patients with CML in chronic phase, accelerated phase, and blast crisis were eligible for this study. The participants with CML (34/122 patients) in a SWOG study published by Blume, et al., had disease beyond first chronic phase. Twenty of those CML patients were treated with BU/CY, and the TBI comparator arm utilized etoposide instead of cyclophosphamide.
How Supplied
There is limited information regarding Busulfan (injection) How Supplied in the drug label.
Storage
There is limited information regarding Busulfan (injection) Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Busulfan (injection) |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Busulfan (injection) |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Busulfan (injection) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Busulfan interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Busulfan (injection) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Busulfan (injection) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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| File:Busulfan.svg | |
| File:Busulfan3d.png | |
| Clinical data | |
|---|---|
| [[Regulation of therapeutic goods |Template:Engvar data]] | |
| Pregnancy category |
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| Routes of administration | Oral, parenteral |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | 80% (oral) |
| Protein binding | 32.4% |
| Metabolism | Hepatic |
| Elimination half-life | 2.5 hours |
| Excretion | ? |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| E number | {{#property:P628}} |
| ECHA InfoCard | {{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value). |
| Chemical and physical data | |
| Formula | C6H14O6S2 |
| Molar mass | 246.304 g/mol |
Overview
Busulfan is a chemotherapy drug that is a cell cycle non-specific alkylating agent (slows the growth of cancer cells). More specifically it belongs to a subclass of alkylating agents known as alkyl sulfonates. It is marketed in the U.S. by GlaxoSmithKline under the brand name Myleran, and has been in clinical use since 1959. Busulfan is also available in an IV formulation marketed as Busulfex by PDL BioPharma, Inc. Its chemical designation is 1,4-Butanediol dimethanesulfonate.
Uses
Currently, its main uses are in bone marrow transplantation, especially in chronic myelogenous leukemia (CML), where it is used as a conditioning drug. Busulfan can control tumor burden but cannot prevent transformation or correct cytogenic abnormalities. Though not as common, it may also be used for Chronic Lymphocytic Leukemia (CLL).
Its mechanism of action through alkylation produces DNA-DNA and DNA-protein cross linking. The resulting covalent bonds inhibit DNA, RNA, and protein synthesis. The inhibition of DNA synthesis subsequently produces a cytotoxic effect.
The drug was recently used in a study to examine the role of platelet-transported serotonin in liver regeneration.[1]
Pill Images
{{#ask: Page Name::Busulfan (injection) |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Toxicity and side effects
Toxicity may include interstitial pulmonary fibrosis, hyperpigmentation, seizures, hepatic (veno-occlusive disease) and wasting syndrome. Phenytoin may be used concurrently to prevent the seizures.
1,4-Butanediol dimethanesulfonate is listed by the IARC as a Group 1 carcinogen.
Busulfan also induces thrombocytopenia, a condition of lowered blood platelet count and activity.
Historical
Busulfan use to be the standard of treatment for Chronic Myeloid Leukemia (CML) until it was replaced with the new gold standard, Imatinib.
References
- ↑ Lesurtel M, Graf R, Aleil B, Walther D, Tian Y, Jochum W, Gachet C, Bader M, Clavien P (2006). "Platelet-derived serotonin mediates liver regeneration". Science. 312 (5770): 104–7. PMID 16601191.
External links
- Myleran (PDF prescribing information)
- Busulfex (PDF prescribing information)
- Detailed information
- Pages with script errors
- CS1 maint: Multiple names: authors list
- Pages with broken file links
- Drugs with non-standard legal status
- E number from Wikidata
- ECHA InfoCard ID from Wikidata
- Chemical articles with unknown parameter in Infobox drug
- Articles without EBI source
- Chemical pages without ChemSpiderID
- Articles without KEGG source
- Articles without InChI source
- Articles without UNII source
- Drug has EMA link
- Articles containing unverified chemical infoboxes
- Chemotherapeutic agents
- Orphan drugs