Leukeran: Targeted Chemotherapy for Hematologic Cancers
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Synonyms | |||
Leukeran (chlorambucil) is an alkylating antineoplastic agent specifically formulated for the treatment of various hematologic malignancies. As a cornerstone of chemotherapy regimens for certain leukemias and lymphomas, it offers a well-established mechanism of action that interferes with DNA replication and transcription in rapidly dividing cells. Its oral administration provides a convenient treatment option, often utilized in both induction and maintenance phases of therapy. This drug represents a critical tool in the oncologist’s arsenal, with a decades-long history of clinical use supporting its efficacy and safety profile when administered under expert supervision.
Features
- Active ingredient: Chlorambucil (2.0 mg scored tablets)
- Pharmacologic class: Nitrogen mustard alkylating agent
- Administration route: Oral
- Mechanism: Cross-links DNA strands, inhibiting cell division
- Bioavailability: Approximately 70-90% after oral administration
- Half-life: 1.5 hours (terminal half-life)
- Metabolism: Hepatic via β-oxidation
- Excretion: Primarily renal (50-60% within 24 hours)
Benefits
- Provides targeted cytotoxic activity against malignant lymphocytes and other rapidly dividing cells
- Enables convenient oral administration compared to intravenous alternatives
- Demonstrates established efficacy in chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphomas
- Offers flexible dosing regimens adaptable to individual patient tolerance and response
- May be used as monotherapy or in combination regimens
- Supports long-term disease management in maintenance therapy settings
Common use
Leukeran is primarily indicated for the treatment of chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, and non-Hodgkin lymphomas (particularly follicular lymphoma). It may also be used off-label for certain autoimmune conditions requiring immunosuppression, such as nephrotic syndrome or rheumatoid arthritis refractory to conventional treatments. The drug is typically reserved for patients who are not candidates for more aggressive chemotherapy regimens or as part of combination therapy protocols. Clinical decision-making involves careful consideration of disease stage, patient performance status, and potential alternative treatments.
Dosage and direction
Dosage must be individualized based on patient weight, hematologic profile, and specific malignancy being treated. For CLL, initial doses typically range from 0.1-0.2 mg/kg/day for 3-6 weeks, with maintenance therapy adjusted according to response and toxicity. Alternative intermittent dosing schedules (e.g., 0.4 mg/kg increased by 0.1 mg/kg every 2 weeks) may be employed. Tablets should be taken whole with water, preferably at the same time each day, with or without food. Regular blood count monitoring is essential throughout treatment, with dosage adjustments made based on nadir counts and clinical response.
Precautions
Patients should be monitored for myelosuppression with weekly complete blood counts during initial therapy and regularly thereafter. Liver and kidney function should be assessed before and during treatment. Use with caution in patients with history of seizures or head trauma due to potential neurotoxicity. Secondary malignancies have been reported with long-term use. Patients should avoid vaccination with live vaccines during treatment and for at least 3 months thereafter. Adequate hydration should be maintained to reduce the risk of hyperuricemia. Women of childbearing potential and men should use effective contraception during and for at least 6 months after treatment.
Contraindications
Leukeran is contraindicated in patients with demonstrated hypersensitivity to chlorambucil or other alkylating agents. It should not be administered to patients with severe bone marrow suppression (unless the disease involves bone marrow) or those who have demonstrated resistance to previous therapy with the drug. Use is contraindicated during pregnancy (Category D) and breastfeeding. The drug should not be administered to patients with active infections unless the potential benefit outweighs the risk. Caution is required in patients with history of seizures or head trauma.
Possible side effect
Common adverse reactions include bone marrow suppression (anemia, leukopenia, thrombocytopenia), nausea, vomiting, and fatigue. Gastrointestinal disturbances such as diarrhea, oral ulceration, and abdominal pain may occur. Dermatological reactions including rash and urticaria have been reported. Neurological effects may include tremors, muscle twitching, confusion, and seizures (particularly at high doses). Pulmonary fibrosis and hepatotoxicity are rare but serious complications. Secondary malignancies, particularly acute myeloid leukemia, have been associated with long-term use. Allergic reactions, including fever and skin reactions, may occur.
Drug interaction
Leukeran may interact with other myelosuppressive agents, increasing the risk of bone marrow toxicity. Concurrent use with live vaccines may diminish vaccine efficacy and increase adverse reactions. Drugs that affect hepatic enzymes may alter chlorambucil metabolism. Anticoagulants may require dosage adjustment due to potential effects on coagulation parameters. Concurrent use with other nephrotoxic agents may enhance renal toxicity. Phenobarbital may increase chlorambucil metabolism, reducing its efficacy. Allopurinol may increase the risk of bone marrow suppression.
Missed dose
If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should never double the dose to make up for a missed one. Healthcare providers should be informed about any missed doses, as this may affect treatment monitoring schedules. Consistent dosing is important for maintaining therapeutic levels, so patients should establish routines to minimize missed doses.
Overdose
Overdose may manifest as pancytopenia, nausea, vomiting, epileptiform seizures, and irreversible bone marrow failure. Symptoms may be delayed due to the drug’s mechanism of action. Management involves immediate discontinuation of the drug and supportive care, including transfusions of blood products and antimicrobial therapy for infections. Hemodialysis is not effective due to high protein binding. There is no specific antidote. Hospitalization with intensive supportive care is required, with particular attention to managing infections and bleeding complications. Long-term monitoring for delayed effects on bone marrow function is essential.
Storage
Store at controlled room temperature (20-25°C or 68-77°F) in the original container. Protect from light and moisture. Keep tightly closed and out of reach of children and pets. Do not store in bathroom or kitchen where humidity and temperature variations may occur. Tablets should not be removed from their blister packaging until immediately before use. Proper disposal of unused medication is essential, preferably through take-back programs or following specific disposal instructions to prevent environmental contamination.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by qualified healthcare professionals based on individual patient circumstances. The prescribing physician should be consulted for complete information regarding indications, dosage, warnings, and precautions. Patients should not alter their treatment regimen without medical supervision. While every effort has been made to ensure accuracy, medical knowledge evolves and the most current prescribing information should always be consulted.
Reviews
Clinical studies have demonstrated Leukeran’s efficacy in achieving remissions in approximately 70% of previously untreated CLL patients, with median response durations of 18-24 months. In follicular lymphoma, response rates of 60-75% have been reported, though complete responses are less common. Many hematologists appreciate its oral administration and generally manageable toxicity profile compared to more aggressive regimens. However, specialists note the importance of careful patient selection and monitoring due to the risk of myelosuppression and secondary malignancies. Long-term follow-up data support its role in maintenance therapy for appropriate patients, though newer targeted agents have altered treatment algorithms for some indications.