Busulfan

Busulfan is a chemotherapy drug approved to treat chronic myelogenous leukemia (CML). The approved use depends on the specific product and form:

• Myleran (oral tablet): Palliative treatment of chronic myelogenous leukemia (CML) — used to control the disease and manage symptoms in adults and children
• Busulfex (intravenous injection): Used in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation (donor stem cell transplant) for CML
• Busulfan Injection (intravenous): Used in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for CML

Busulfan is a bifunctional alkylating agent — it has two reactive chemical ends that attach to DNA inside cells. When it reaches cancer cells, it releases reactive particles that chemically bond to the DNA strands, damaging them and preventing the cell from replicating. This DNA damage is what drives busulfan's ability to kill cancer cells.

Busulfan is a small, highly fat-soluble molecule that can cross the blood-brain barrier. It is broken down mainly in the liver through a process involving glutathione (a natural compound in the body), and its breakdown products do not carry the same cancer-killing activity as the parent drug.

How busulfan is taken depends entirely on the product and clinical setting — these regimens are not interchangeable.

• Myleran (tablet): Taken by mouth once daily. Dosing is based on body weight, and your doctor will adjust it based on how your white blood cell count responds. Treatment is typically stopped when counts fall to a target level, then may be restarted during relapse.
• Busulfex / Busulfan Injection (IV): Administered by healthcare professionals as a two-hour intravenous infusion every six hours for four days (16 total doses) through a central venous catheter. This is done only in a hospital or transplant center as part of a pre-transplant conditioning regimen.

Always follow your prescriber's exact dosing schedule. Never adjust or stop the dose on your own.

Busulfan commonly causes a wide range of side effects, especially when used at high doses before a transplant:

• Severe low blood counts (low white cells, platelets, and red blood cells) — occurs in all patients receiving IV busulfan
• Nausea, vomiting, and diarrhea
• Mouth sores (mucositis/stomatitis)
• Loss of appetite
• Fever and chills
• Insomnia and anxiety
• Skin rash or itching
• Low magnesium, potassium, and other electrolyte levels

Serious reactions that require immediate medical attention include seizures, signs of liver damage (yellowing of skin or eyes, severe abdominal pain), serious lung problems (persistent cough, shortness of breath), and signs of infection. In children, abdominal pain and vomiting followed by breathing difficulty may signal a dangerous buildup of fluid around the heart (cardiac tamponade).

• Bone marrow suppression: The most serious and universal risk — all patients receiving IV busulfan develop dangerously low blood counts. Prolonged suppression can be life-threatening without a stem cell transplant and supportive care. Myleran must be stopped before counts fall too low.
• Seizures: High-dose busulfan can cause seizures. Anti-seizure medication must be started before IV treatment and continued for 24 hours after the last dose. Extra caution is needed in patients with a prior seizure history or head trauma.
• Hepatic veno-occlusive disease (HVOD): A serious blockage of blood flow in the liver that can be fatal. Risk is higher with elevated busulfan blood levels. Liver function must be monitored daily during transplant conditioning.
• Lung damage (bronchopulmonary dysplasia): A rare but serious complication of chronic busulfan therapy. Symptoms — cough, shortness of breath, low-grade fever — can appear months to years after treatment and may be fatal.
• Secondary cancers: Long-term busulfan use has been associated with the development of acute leukemia. The World Health Organization recognizes a causal link between busulfan exposure and secondary malignancies.
• Fetal harm: Busulfan can seriously harm a developing baby. Effective contraception is required during and after treatment.
• Cardiac tamponade (children): Reported in pediatric patients with thalassemia receiving high-dose busulfan and cyclophosphamide — often fatal. Abdominal pain and vomiting are early warning signs.

Busulfan's levels in the blood can be significantly affected by other medications, which can increase toxicity or reduce effectiveness:

• Metronidazole (an antibiotic) — reduces how fast the body clears busulfan, raising the risk of serious toxicity
• Itraconazole (an antifungal) — reduces busulfan clearance by up to 25%, increasing exposure
• Iron chelating agents (e.g., deferasirox) — reduce busulfan clearance; should be stopped well before busulfan injection treatment begins
• Acetaminophen (Tylenol) — lowers glutathione levels in the body, which can reduce busulfan clearance; avoid within 72 hours before or during busulfan injection treatment
• Phenytoin (an anti-seizure drug) — increases busulfan clearance by 15% or more, potentially lowering busulfan levels and effectiveness

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Myleran should not be used unless a firm diagnosis of CML has been established
• Do not use busulfan if you have had a serious allergic reaction to it or any of its components
• Tell your doctor about all previous chemotherapy or radiation therapy — prior treatment increases the risk of severe bone marrow suppression
• Tell your doctor if you have a history of seizures or head injury before starting IV busulfan
• Busulfan can cause serious fetal harm — do not use during pregnancy unless clearly necessary, and discuss risks with your doctor
• Women of reproductive potential should use effective contraception during treatment and for 6 months after stopping busulfan injection
• Men should use effective contraception during treatment and for 3 months after stopping busulfan injection
• Do not breastfeed while taking busulfan
• Busulfan can cause temporary or permanent infertility in both men and women — discuss fertility preservation with your doctor before starting treatment
• The effectiveness of IV busulfan specifically for CML has not been studied formally in pediatric patients; pediatric dosing in transplant settings is based on pharmacokinetic studies and requires therapeutic drug monitoring

There is no specific antidote for busulfan overdose. The main risks are severe bone marrow failure and dangerously low blood counts, which must be managed with close monitoring and supportive medical care. If a recent oral overdose is suspected, inducing vomiting or using gastric lavage followed by activated charcoal may be considered.

Busulfan's primary measurable effect is suppression of blood cell production by damaging the bone marrow. In all patients receiving the recommended IV dose before transplant, absolute neutrophil counts (infection-fighting white blood cells) fall below a critical level within a median of 4 days after transplant. Platelet counts also drop to critically low levels within 5 to 6 days in the vast majority of patients. This profound suppression of the bone marrow is the intended effect before a stem cell transplant, but it requires intensive supportive care to prevent fatal complications.

Busulfan is well absorbed when taken by mouth, with an average bioavailability of about 80% in adults (somewhat lower in young children). It is a small, highly fat-soluble molecule that easily crosses the blood-brain barrier and reaches the cerebrospinal fluid at levels similar to those in the blood. The drug is primarily broken down in the liver through conjugation with glutathione, producing at least 12 metabolites that do not have cancer-killing activity. Its half-life — the time for blood levels to drop by half — is approximately 2.6 hours. Less than 2% of the drug is excreted unchanged in the urine, with the remainder eliminated as metabolites, primarily through the urine over the first 48 hours.

stored under refrigerated conditions between 2° to 8°C (36° to 46°F). refrigerated conditions (2° to 8°C) for up to 12 hours but the infusion must be completed within that time.