Busulfan: Dosage, Uses, and Side Effects Explained

Introduction

Busulfan is a potent alkylating agent and cytotoxic chemotherapy drug used in the treatment of various blood cancers and as part of conditioning regimens for hematopoietic stem cell transplantation. First approved by the FDA in 1959, busulfan has a long history of use in oncology and hematology.

Chemical Properties

Busulfan, with the molecular formula C6H14O6S2, is structurally classified as an alkyl sulfonate. It is a bifunctional alkylating agent, meaning it has two reactive groups that can form covalent bonds with DNA. Busulfan is a white, crystalline solid with a melting point of 115-118°C and is soluble in water and various organic solvents.

Mechanism of Action

As an alkylating agent, busulfan exerts its cytotoxic effects by cross-linking DNA strands, leading to DNA damage and cell death. It has a selective immunosuppressive effect on the bone marrow, making it useful in conditioning regimens before stem cell transplantation. Busulfan acts in a cell cycle-nonspecific manner, meaning it can damage cells in any phase of the cell cycle.

Medical Uses

Busulfan is primarily used in the treatment of chronic myelogenous leukemia (CML) and other myeloproliferative disorders. It is also an important component of high-dose conditioning regimens prior to allogeneic hematopoietic stem cell transplantation for various hematologic malignancies. Off-label uses include treatment of polycythemia vera and essential thrombocythemia.

Administration and Dosage

Busulfan can be administered orally or intravenously. Oral busulfan is available as 2 mg tablets under the brand name Myleran®. Intravenous busulfan is given as a 2-hour infusion every 6 hours for 4 days, typically in combination with other chemotherapy drugs like cyclophosphamide or fludarabine. Dosage is based on body weight and may require adjustments based on pharmacokinetic monitoring.

Side Effects and Toxicity

Common side effects of busulfan include nausea, vomiting, diarrhea, mouth sores, hair loss, and fatigue. Serious toxicities can affect various organ systems, such as pulmonary toxicity (e.g., interstitial pneumonitis), hepatotoxicity (e.g., sinusoidal obstruction syndrome), and neurotoxicity (e.g., seizures). Long-term effects may include infertility, endocrine dysfunction, and secondary malignancies.

Precautions and Contraindications

Before starting busulfan therapy, patients should undergo a thorough medical evaluation, including baseline pulmonary function tests and liver function tests. Regular monitoring of blood counts, liver enzymes, and pulmonary function is necessary during treatment. Busulfan is contraindicated in patients with severe pulmonary or hepatic impairment and should be used with caution in elderly patients or those with prior radiation exposure.

Drug Interactions

Busulfan can interact with various medications, including acetaminophen, itraconazole, metronidazole, and phenytoin. Concomitant use of busulfan with other myelosuppressive agents or radiation therapy may increase the risk of toxicity. Patients should inform their healthcare providers about all medications, supplements, and herbal products they are taking before starting busulfan.

References

1. Busulfan. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [ Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
2. Busulfan: A Review of its Toxicity and Protective Effects. Therapeutic Drug Monitoring. 2017;39(6):598-606.
3. Busulfan. StatPearls [ Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Feb 15.