Description

Leukeran (Chlorambucil) Overview

What is Leukeran?

Leukeran is a medication that contains chlorambucil, an alkylating agent used primarily in the treatment of certain cancers, including chronic lymphocytic leukemia and various lymphomas.

Dosage Form

• Strength: 2 mg tablets
• Pack Size: 25 tablets per pack

Availability in Pakistan

Pricing

• Approximate Cost: ₨10,000 for a pack of 25 tablets (as of August 16, 2023)

Where to Buy

• Pharmacies: Available at licensed pharmacies in Pakistan with a valid prescription.

Composition

Active Ingredient

• Chlorambucil: 2 mg per tablet

Inactive Ingredients

• Common excipients may include colloidal silicon dioxide and titanium dioxide, among others.

Mechanism of Action

Chlorambucil works by:

• Interfering with DNA Replication: It disrupts the process of cell division, which helps to slow or stop the growth of cancer cells.

Dosage and Administration

Recommended Use

• Administration: Taken orally, usually on an empty stomach for better absorption.
• Dosage: Determined by a healthcare professional based on the patient’s condition and weight.

Important Considerations

Side Effects

• Potential side effects may include nausea, vomiting, and bone marrow suppression. Monitoring by a healthcare provider is essential.

Consultation

• Always consult a healthcare professional for personalized advice regarding dosage, potential interactions, and monitoring during treatment.

Conclusion

Leukeran (chlorambucil) is a vital medication in the management of certain cancers. Its availability in Pakistan makes it accessible for patients in need of treatment, but it should always be used under the guidance of a healthcare professional.

Key Benefits of Leukeran (Chlorambucil)

1. Effective Cancer Treatment: Leukeran is primarily used to treat specific types of cancer, including chronic lymphocytic leukemia and certain lymphomas, by slowing or stopping the growth of cancer cells.
2. Alkylating Agent: As part of the alkylating agents class, chlorambucil works by interfering with DNA replication, which is crucial in the management of malignancies.
3. Palliative Care: While not curative, it can provide significant palliation for patients suffering from various hematological malignancies, improving quality of life.
4. Oral Administration: The medication is available in tablet form, facilitating easier administration compared to intravenous treatments.
5. Long History of Use: Chlorambucil has been in use since 1957, providing a well-documented profile of efficacy and safety when monitored properly.

Key Ingredients in Leukeran

• Active Ingredient:
  • Chlorambucil: Each tablet contains 2 mg of chlorambucil, which is the primary active component responsible for its therapeutic effects.
• Inactive Ingredients:
  • Colloidal Silicon Dioxide
  • Hypromellose
  • Lactose (anhydrous)
  • Macrogol/PEG 400
  • Microcrystalline Cellulose
  • Red Iron Oxide
  • Stearic Acid
  • Titanium Dioxide
  • Yellow Iron Oxide                                                                                                                               
    

    Chlorambucil

    Chemotherapy medication for leukemia and lymphoma

    More

    Trade names

    Leukeran, others

    Main medical uses

    Treats chronic lymphocytic leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma

    Side effects

    Includes bone marrow suppression, increased risk of cancer, infertility, and allergic reactions
    Chlorambucil, the active ingredient in Leukeran, functions as an alkylating agent with a specific mechanism of action that targets cancer cells.

    Mechanism of Action

    1. Alkylation of DNA: Chlorambucil works by forming covalent bonds with DNA, leading to alkylation. This process disrupts the normal structure and function of DNA, which is essential for cell replication and division.
    2. Interference with DNA Replication: By damaging the DNA, chlorambucil inhibits the synthesis of DNA and RNA, thereby preventing cancer cells from dividing and proliferating. This action is crucial for its effectiveness in treating cancers such as chronic lymphocytic leukemia and lymphomas.
    3. Induction of Apoptosis: Chlorambucil also promotes apoptosis (programmed cell death) in cancer cells. This occurs through the accumulation of the protein p53 in the cytosol, which subsequently activates Bax, a pro-apoptotic factor. This pathway ensures that damaged or dysfunctional cells are eliminated from the body, contributing to the therapeutic effects of the drug.
    4. Bifunctional Nature: As a bifunctional alkylating agent, chlorambucil can bind to multiple sites on DNA, enhancing its ability to cause cross-linking of DNA strands. This cross-linking is a critical factor in its effectiveness against cancer cells, as it further complicates DNA repair mechanisms and promotes cell death.
    
    Key Precautions with Leukeran (Chlorambucil)

    1. Bone Marrow Suppression: Leukeran can cause a significant reduction in blood cell counts, particularly neutrophils, leading to an increased risk of infections. Regular monitoring of blood counts is essential.
    2. Cancer Risk: Treatment with Leukeran may increase the risk of developing certain types of secondary cancers. Patients should be monitored closely for any new malignancies.
    3. Fetal Harm: Leukeran can cause harm to the developing fetus and is contraindicated during pregnancy. Effective contraception is necessary for both male and female patients.
    4. Infertility: Leukeran may cause temporary or permanent infertility in both men and women. Patients should discuss fertility preservation options with their healthcare provider before starting treatment.
    5. Allergic Reactions: Patients with a known allergy to Leukeran or other alkylating agents should not receive this medication.
    6. Liver Problems: Leukeran can cause liver damage. Patients with pre-existing liver problems may require a lower dosage or alternative treatment.
    7. Seizures: Patients with a history of seizures or seizure disorders should inform their doctor before starting Leukeran, as certain medications may increase the risk of seizures when taken concurrently.

    Dietary Restrictions

    • Alcohol: While there are no known interactions between Leukeran and alcohol, drinking alcohol may increase the risk of certain side effects, such as nausea, vomiting, and nerve damage. Patients should discuss the appropriate amount of alcohol, if any, with their healthcare provider.
    • Food: Leukeran should be taken on an empty stomach, at least one hour before or three hours after meals, for optimal absorption.

    Medications That May Interact with Leukeran

    • Nalidixic acid: Do not take this medication with Leukeran.
    • Fingolimod: Concomitant use increases the risk of infection due to immunosuppressive effects. Modify therapy and monitor closely.
    • Lomustine: Either drug may increase the toxicity of the other due to pharmacodynamic synergism. Use caution and monitor closely, as there is an increased risk of myelosuppression.

    General Considerations

    • Leukeran is primarily metabolized by the liver, so medications that affect liver function may alter its metabolism.
    • Drugs that suppress the immune system or increase the risk of infection may have additive effects when used with Leukeran.
    • Medications that increase the risk of bleeding or bruising may have an additive effect when used with Leukeran.

    Importance of Disclosure

    It is crucial for patients taking Leukeran to inform their healthcare providers about all medications they are currently using, including prescription drugs, over-the-counter medications, vitamins, and herbal supplements. This allows for proper monitoring and adjustment of treatment plans to minimize the risk of interactions and optimize the effectiveness of Leukeran therapy.

    Major Interactions with Other Cancer Medications

    1. Lomustine: Both drugs can increase each other’s toxicity, particularly leading to additive myelosuppression. Caution and close monitoring are advised when these medications are used together.
    2. Obinutuzumab: The combination may increase the toxicity of obinutuzumab, leading to thrombocytopenia (low platelet count) and potential hemorrhage. It is recommended to modify therapy and monitor closely.
    3. Ofatumumab: Co-administration can enhance the immunosuppressive effects of both drugs, increasing the risk of infection. Caution is advised when using these medications together.
    4. Olaparib: This combination may result in pharmacodynamic synergism, heightening the risk of myelosuppressive toxicity. Monitoring is necessary when these drugs are administered together.
    5. Oxaliplatin: There is a risk of increased toxicity when chlorambucil is used with oxaliplatin, leading to additive myelosuppression. Caution and monitoring are recommended.
    6. Acalbrutinib: The combination can increase the toxicity of both drugs. Close monitoring is advised due to the potential for enhanced side effects.

    General Considerations

    • Myelosuppression: Many interactions lead to increased risk of myelosuppression, which can result in anemia, leukopenia, and thrombocytopenia. Regular blood monitoring is essential when combining these therapies.
    • Immunosuppressive Effects: Combining chlorambucil with other immunosuppressive agents can enhance the risk of infections due to compounded effects on the immune system.
    • Pharmacodynamic Synergism: Several combinations may lead to synergistic effects, increasing the overall toxicity and necessitating careful management and dose adjustments.

    Use During Pregnancy

    • Risk to Fetus: Chlorambucil is classified as a Category D medication by both the AU TGA and the US FDA, indicating that there is positive evidence of human fetal risk based on adverse reaction data. It can harm a developing fetus and is associated with urogenital malformations, including renal agenesis, as observed in animal studies.
    • Recommendation: The drug should only be used during pregnancy if the potential benefits outweigh the risks. Women of childbearing potential are advised to avoid becoming pregnant while on this medication. If a patient becomes pregnant while taking chlorambucil, they should be informed about the potential risks to the fetus.

    Use During Breastfeeding

    • Excretion in Breast Milk: There is limited information regarding the excretion of chlorambucil in human breast milk, and its effects on a nursing infant are unknown. Most sources consider breastfeeding to be contraindicated during maternal therapy with cytotoxic antineoplastic drugs, particularly alkylating agents like chlorambucil.
    • Recommendation: A decision should be made to either discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Since chemotherapy can adversely affect the normal microbiome and chemical makeup of breast milk, it may also lead to difficulties in breastfeeding.

    There are significant risks associated with taking Leukeran (chlorambucil) during pregnancy:

    Fetal Harm

    • Chlorambucil can cause harm to a developing fetus.
    • Unilateral renal agenesis (absence of one kidney) has been observed in offspring whose mothers received chlorambucil during the first trimester.
    • Urogenital malformations, including absence of a kidney, were found in animal studies.

    Pregnancy Category

    • Chlorambucil is classified as a Category D medication by both the AU TGA and the US FDA, indicating positive evidence of human fetal risk.

    Recommendations

    • Chlorambucil should only be used during pregnancy if the potential benefits outweigh the risks.
    • Women of childbearing potential should be advised to avoid becoming pregnant while on this medication.
    • If a patient becomes pregnant while taking chlorambucil, they should be informed about the potential risks to the fetus.

    Dosage of Leukeran (Chlorambucil)

    • Administration: Chlorambucil is typically taken orally, usually once daily. The specific dosage is determined by the patient’s medical condition, body weight, and response to treatment.
    • Duration: Treatment may last from 3 to 6 weeks, depending on the individual treatment plan set by the healthcare provider.
    • Missed Dose: If a dose is missed, it should be taken as soon as remembered, unless it is almost time for the next dose. In that case, the missed dose should be skipped, and the regular schedule resumed. Doubling doses is not recommended.

    Storage of Leukeran

    • Temperature: Store Leukeran in the refrigerator at temperatures between 36°F to 46°F (2°C to 8°C). Do not freeze the medication.
    • Protection: Keep the medication in its original container, tightly closed, and protected from light and moisture.
    • Safety: Ensure that the medication is kept out of reach of children and pets, and dispose of any outdated or unused medication properly.

    Reviews and Patient Feedback

    While specific reviews from patients are not included in the search results, general feedback on chlorambucil (Leukeran) indicates a mixed experience:

    • Efficacy: Many patients report that chlorambucil is effective in managing their cancer symptoms, particularly in chronic lymphocytic leukemia and certain lymphomas.
    • Side Effects: Common side effects include nausea, vomiting, and bone marrow suppression, which can lead to low blood cell counts. Some patients express concerns about the risk of infections and the need for regular blood monitoring.
    • Quality of Life: Some patients have noted improvements in their quality of life during treatment, while others have reported challenges related to side effects.