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Chlorambucil: Pediatric drug information

Chlorambucil: Pediatric drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Chlorambucil: Drug information" and "Chlorambucil: Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Bone marrow suppression:

Chlorambucil can severely suppress bone marrow function.

Adverse effects:

Chlorambucil is a carcinogen in humans. Chlorambucil is probably mutagenic and teratogenic in humans. Chlorambucil produces human infertility.

Brand Names: US
  • Leukeran
Brand Names: Canada
  • Leukeran
Therapeutic Category
  • Antineoplastic Agent, Alkylating Agent;
  • Antineoplastic Agent, Alkylating Agent (Nitrogen Mustard)
Dosing: Pediatric

Note: For oncologic uses, dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.

Hodgkin lymphoma

Hodgkin lymphoma: Limited data available: Infants ≥7 months, Children, and Adolescents: ChlVPP regimen: Oral: 6 mg/m2/day on days 1 to 14 of a 28-day cycle for 6 to 10 cycles in combination with vinblastine, procarbazine, and prednisolone (Ref)

Nephrotic syndrome; frequently relapsing steroid sensitive

Nephrotic syndrome; frequently relapsing steroid sensitive: Limited data available: Children and Adolescents: Oral: 0.1 to 0.2 mg/kg/day once daily for 8 weeks (maximum cumulative dose: 11.2 mg/kg) (Ref); Note: Chlorambucil is not a preferred agent due to a higher incidence of adverse effects with no greater efficacy (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management.

Adult:

Skin reactions: Discontinue treatment

Hematologic:

WBC or platelets below normal: Reduce dose

Severely depressed WBC or platelet counts: Discontinue

Persistently low neutrophil or platelet counts or peripheral lymphocytosis: May be suggestive of bone marrow infiltration; if infiltration confirmed, do not exceed 0.1 mg/kg/day in adults

Concurrent or within 4 weeks (before or after) of chemotherapy/radiotherapy: Initiate treatment cautiously; reduce dose; monitor closely.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, based on experience in adult patients, renal elimination of unchanged chlorambucil and active metabolite (phenylacetic acid mustard) is minimal and renal impairment is not likely to affect elimination.

Dosing: Liver Impairment: Pediatric

Chlorambucil undergoes extensive hepatic metabolism. Although dosage reduction should be considered in patients with hepatic impairment, there are no dosage adjustments provided in the manufacturer's labeling (data is insufficient).

Dosing: Adult

(For additional information see "Chlorambucil: Drug information")

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia:

Chronic lymphocytic leukemia in previously untreated patients (off-label dosing): Oral: 0.4 mg/kg day 1 every 2 weeks; if tolerated may increase by 0.1 mg/kg with each treatment course to a maximum dose of 0.8 mg/kg and maximum of 24 cycles (Ref) or 0.5 mg/kg on days 1 and 15 every 28 days for 6 cycles (Ref).

Chronic lymphocytic leukemia in previously untreated patients (off-label combinations):

Chlorambucil-obinutuzumab: Oral: 0.5 mg/kg on days 1 and 15 every 28 days for 6 cycles (Ref).

Chlorambucil-ofatumumab: Oral: 10 mg/m2 once daily for 7 days (days 1 to 7) every 28 days for a minimum of 3 cycles and up to 12 cycles or best response (clinical response that did not improve after 3 additional cycles); if necessary, reduce dose to 7.5 mg/m2/day and then to 5 mg/m2/day for hematologic toxicity (Ref).

Chlorambucil-rituximab: Oral: 10 mg/m2 once daily for 7 days (days 1 to 7) every 28 days for 6 to 12 cycles (Ref).

Manufacturer’s labeling: Oral: 0.1 mg/kg/day for 3 to 6 weeks or 0.4 mg/kg pulsed doses administered intermittently, biweekly, or monthly (increased by 0.1 mg/kg/dose until response/toxicity observed). Note: Reduce initial dose if full-dose radiation or myelotoxic drugs have been administered within the last 4 weeks. With bone marrow lymphocytic infiltration involvement in chronic lymphocytic leukemia, the manufacturer recommends a maximum dose of 0.1 mg/kg/day; while short treatment courses are preferred, if maintenance therapy is required, the manufacturer recommends a maximum dose of 0.1 mg/kg/day.

Hodgkin lymphoma

Hodgkin lymphoma: Note: Reduce initial dose if full-dose radiation or myelotoxic drugs have been administered within the last 4 weeks. With bone marrow lymphocytic infiltration involvement in Hodgkin lymphoma, the manufacturer recommends a maximum dose of 0.1 mg/kg/day; while short treatment courses are preferred, if maintenance therapy is required, the manufacturer recommends a maximum dose of 0.1 mg/kg/day.

ChlVPP regimen: Oral: 6 mg/m2 once daily (maximum 10 mg/day) on days 1 to 14 every 28 days (in combination with vinblastine, procarbazine, and prednisolone) until complete remission plus 2 cycles (Ref) or 6 mg/m2 once daily on days 1 to 14 every 28 days (in combination with vinblastine, procarbazine, and prednisone) for 6 cycles (Ref).

Necrobiotic xanthogranuloma

Necrobiotic xanthogranuloma (off-label use; based on limited data): Oral: 2 to 4 mg once daily either with or without systemic corticosteroids (Ref) or 10 mg once daily for 14 days of a 28-day treatment cycle for 8 cycles (Ref) or 10 mg once daily, reduced to 2 mg once daily (in combination with prednisone) (Ref).

Non-Hodgkin lymphomas

Non-Hodgkin lymphomas:

Follicular lymphoma (off-label dosing): Oral: 6 mg/m2 once daily during weeks 1 to 6, followed 8 weeks later (if response occurred) by 6 mg/m2 once daily for 2 weeks of a 4-week cycle for 4 cycles (in combination with rituximab) (Ref).

Mucosa-associated lymphoid tissue lymphoma (off-label dosing): Oral: 6 mg/m2 once daily during weeks 1 to 6, followed by 6 mg/m2 once daily for 2 weeks of a 4-week cycle for up to 4 cycles (in combination with rituximab) (Ref).

Manufacturer’s labeling: Oral: 0.1 mg/kg/day for 3 to 6 weeks. Note: Reduce initial dose if full-dose radiation or myelotoxic drugs have been administered within the last 4 weeks. With bone marrow lymphocytic infiltration involvement in non-Hodgkin lymphoma, the manufacturer recommends a maximum dose of 0.1 mg/kg/day; while short treatment courses are preferred, if maintenance therapy is required, the manufacturer recommends a maximum dose of 0.1 mg/kg/day.

Waldenström macroglobulinemia

Waldenström macroglobulinemia (alternative agent) (off-label use): Oral: 8 mg/m2 (6 mg/m2 in patients >75 years of age) once daily for 10 days every 28 days for up to 12 cycles (Ref) or 0.1 mg/kg/day (continuously) for at least 6 months (Ref) or 0.3 mg/kg/day for 7 days every 6 weeks for at least 6 months (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; however, kidney elimination of unchanged chlorambucil and active metabolite (phenylacetic acid mustard) is minimal and kidney impairment is not likely to affect elimination. The following adjustments have been recommended:

Aronoff 2007:

CrCl >50 mL/minute: No adjustment necessary.

CrCl 10 to 50 mL/minute: Administer 75% of dose.

CrCl <10 mL/minute: Administer 50% of dose.

Peritoneal dialysis (PD): Administer 50% of dose.

Kintzel 1995: Based on the pharmacokinetics, dosage adjustment is not indicated.

Dosing: Liver Impairment: Adult

Chlorambucil undergoes extensive hepatic metabolism. Although dosage reduction should be considered in patients with hepatic impairment, there are no dosage adjustments provided in the manufacturer's labeling (data are insufficient). Monitor patients closely for toxicity.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined.

Central nervous system: Drug fever, peripheral neuropathy

Dermatologic: Allergic skin reaction, skin rash, urticaria

Endocrine & metabolic: Amenorrhea

Gastrointestinal: Diarrhea (infrequent), nausea (infrequent), oral mucosa ulcer (infrequent), vomiting (infrequent)

Genitourinary: Azoospermia, cystitis (sterile), infertility

Hematologic & oncologic: Anemia, bone marrow depression, bone marrow failure (irreversible), leukemia (secondary), leukopenia, lymphocytopenia, malignant neoplasm (secondary), neutropenia (onset: 3 weeks; recovery: 10 days after last dose), pancytopenia, thrombocytopenia

Hepatic: Hepatotoxicity, jaundice

Hypersensitivity: Angioedema, hypersensitivity reaction

Respiratory: Interstitial pneumonitis, pulmonary fibrosis

Miscellaneous: Fever

1%, postmarketing, and/or case reports: Agitation, ataxia, confusion, erythema multiforme, flaccid paralysis, seizure (focal/generalized), hallucination, muscle twitching, myoclonus, SIADH (syndrome of inappropriate antidiuretic hormone secretion), Stevens-Johnson syndrome, toxic epidermal necrolysis, tremor

Contraindications

Hypersensitivity to chlorambucil or any component of the formulation; hypersensitivity to other alkylating agents (may have cross-hypersensitivity); prior (demonstrated) resistance to chlorambucil.

Canadian labeling: Additional contraindications (not in the US labeling): Use within 4 weeks of a full course of radiation or chemotherapy.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Chlorambucil may cause severe bone marrow suppression; neutropenia may be severe. Irreversible bone marrow damage may occur with total doses approaching 6.5 mg/kg. Progressive lymphopenia may develop (recovery is generally rapid after discontinuation).

• Secondary malignancy: Chlorambucil is a human carcinogen; acute myelocytic leukemia and secondary malignancies may be associated with chronic therapy. Duration of treatment and higher cumulative doses are associated with a higher risk for development of leukemia.

• Seizures: Seizures have been observed with chlorambucil; patients with a history of nephrotic syndrome and high pulse doses are at higher risk of seizures. Use with caution in patients with a history of seizure disorder or head trauma.

• Skin reactions: Rare instances of severe skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported.

Other warnings/precautions:

• Vaccines: Avoid administration of live vaccines to immunocompromised patients.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Leukeran: 2 mg

Generic Equivalent Available: US

No

Pricing: US

Tablets (Leukeran Oral)

2 mg (per each): $693.08

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Leukeran: 2 mg

Extemporaneous Preparations

A 2 mg/mL oral suspension may be prepared with tablets. Crush sixty 2 mg tablets in a mortar and reduce to a fine powder. Add small portions of methylcellulose 1% and mix to a uniform paste (total methylcellulose: 30 mL); mix while adding simple syrup in incremental proportions to almost 60 mL; transfer to a graduated cylinder, rinse mortar and pestle with simple syrup, and add quantity of vehicle sufficient to make 60 mL. Transfer contents of graduated cylinder to an amber prescription bottle. Label "shake well", "refrigerate", and "protect from light". Stable for 7 days refrigerated.

Dressman JB and Poust RI. Stability of Allopurinol and of Five Antineoplastics in Suspension. Am J Hosp Pharm. 1983;40(4):616-618.6846371
Nahata MC, Pai VB, and Hipple TF. Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Administration: Pediatric

Oral: May be administered as a single daily dose; preferably on an empty stomach.

Administration: Adult

Oral: May be administered as a single daily dose.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Storage/Stability

Store in refrigerator at 2°C to 8°C (36°F to 46°F).

Use

Treatment of chronic lymphocytic leukemia (CLL), Hodgkin's and non-Hodgkin's lymphoma (FDA approved in adults); has also been used in the treatment of nephrotic syndrome (unresponsive to conventional therapy) and Waldenström's macroglobulinemia

Medication Safety Issues
Sound-alike/look-alike issues:

Chlorambucil may be confused with Chloromycetin (chloramphenicol).

Leukeran may be confused with Alkeran, leucovorin, Leukine, Myleran.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Food Interactions

Absorption is decreased when administered with food. Management: Administer preferably on an empty stomach.

Reproductive Considerations

Patients should avoid becoming pregnant during treatment. In general, patients who could become pregnant should use effective contraception during systemic anticancer therapy and for 3 to 6 months after the last dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 to 6 months after the last dose of systemic anticancer therapy (ESMO [Peccatori 2013]).

Chlorambucil is associated with a high risk of infertility (ESMO [Lambertini 2020]). Chromosomal damage has been documented. Reversible and irreversible sterility (when administered to prepubertal and pubertal males), azoospermia (in adult males), and amenorrhea (in females) have been observed. Fibrosis, vasculitis, and depletion of primordial follicles have been noted on autopsy of the ovaries.

Recommendations are available for fertility preservation of male and female patients to be treated with anticancer agents (ASCO [Oktay 2018]; Klipstein 2020).

Pregnancy Considerations

Outcome data following maternal use of chlorambucil during pregnancy are limited (NTP 2013). Case reports have noted adverse renal effects (unilateral agenesis) in the newborn following first trimester exposure.

The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, when used for the treatment of cancer, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]). Guidance is available for pregnant patients with hematologic malignancies; use of chlorambucil is not recommended (Lishner 2016).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).

Monitoring Parameters

Liver function tests, CBC with differential (weekly, with WBC monitored weekly during the first 3 to 6 weeks of treatment)

Mechanism of Action

Chlorambucil is an alkylating agent that interferes with DNA replication and RNA transcription by alkylation and cross-linking the strands of DNA, inducing cellular apoptosis.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid and complete (>70%) from GI tract; reduced with food

Distribution: Vd: ~0.31 L/kg

Protein binding: ~99%; primarily to albumin

Metabolism: Hepatic (extensively); primarily to active metabolite, phenylacetic acid mustard; chlorambucil and phenylacetic acid mustard undergo oxidative degradation

Half-life elimination: Chlorambucil: ~1.5 hours; Phenylacetic acid mustard: 1.8 ± 0.4 hours

Time to peak, plasma: Chlorambucil: Within 1 hour; Phenylacetic acid mustard: 1.9 ± 0.7 hours

Excretion: Urine (~20% to 60% within 24 hours, primarily as inactive metabolites, <1% as unchanged drug or phenylacetic acid mustard)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Leukeran;
  • (AR) Argentina: Leukeran;
  • (AT) Austria: Leukeran;
  • (AU) Australia: Leukeran;
  • (BD) Bangladesh: Leukeran;
  • (BE) Belgium: Leukeran;
  • (BG) Bulgaria: Leukeran;
  • (BR) Brazil: Leukeran;
  • (CH) Switzerland: Leukeran;
  • (CL) Chile: Clorambucilo | Leukeran;
  • (CN) China: Leukeran;
  • (CO) Colombia: Leukeran;
  • (CZ) Czech Republic: Chlorobutin | Leukeran;
  • (DE) Germany: Leukeran;
  • (DO) Dominican Republic: Leukeran;
  • (EC) Ecuador: Leukeran;
  • (EE) Estonia: Leukeran;
  • (EG) Egypt: Leukeran;
  • (ES) Spain: Clorambucilo aspen | Leukeran;
  • (FI) Finland: Chlorambusil | Leukeran;
  • (FR) France: Chloraminophene;
  • (GB) United Kingdom: Leukeran;
  • (GR) Greece: Leukeran;
  • (HK) Hong Kong: Leukeran;
  • (HU) Hungary: Chlorbutin | Leukeran;
  • (IE) Ireland: Leukeran;
  • (IL) Israel: Leukeran;
  • (IN) India: Celkeran | Chloramax | Clokeran | Leukeran;
  • (IT) Italy: Leukeran;
  • (JO) Jordan: Leukeran;
  • (KE) Kenya: Leukeran;
  • (KR) Korea, Republic of: Leukeran;
  • (KW) Kuwait: Leukeran;
  • (LB) Lebanon: Leukeran;
  • (LT) Lithuania: Chlorobutin | Leukeran;
  • (LU) Luxembourg: Leukeran;
  • (LV) Latvia: Chlorobutin | Leukeran;
  • (MX) Mexico: Leukeran;
  • (MY) Malaysia: Leukeran;
  • (NL) Netherlands: Leukeran;
  • (NO) Norway: Leukeran;
  • (NZ) New Zealand: Leukeran;
  • (PH) Philippines: Leukeran;
  • (PL) Poland: Chlorobutin | Leukeran;
  • (PR) Puerto Rico: Leukeran;
  • (PT) Portugal: Leukeran;
  • (QA) Qatar: Leukeran;
  • (RO) Romania: Leukeran;
  • (RU) Russian Federation: Chlorbutin | Chlorobutin | Leukeran | Loramyl;
  • (SA) Saudi Arabia: Leukeran;
  • (SE) Sweden: Leukeran;
  • (SG) Singapore: Leukeran;
  • (SI) Slovenia: Leukeran;
  • (SK) Slovakia: Leukeran;
  • (SR) Suriname: Leukeran;
  • (TH) Thailand: Leukeran;
  • (TN) Tunisia: Leukeran;
  • (TR) Turkey: Leukeran;
  • (TW) Taiwan: Leukeran;
  • (UA) Ukraine: Leukeran;
  • (UY) Uruguay: Leukeran | Linfoxan;
  • (ZA) South Africa: Leukeran
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