Chlorambucil can severely suppress bone marrow function.
Chlorambucil is a carcinogen in humans. Chlorambucil is probably mutagenic and teratogenic in humans. Chlorambucil produces human infertility.
Note: Reduce initial dose if full-dose radiation or myelotoxic drugs have been administered within the last month. With bone marrow lymphocytic infiltration involvement (in chronic lymphocytic leukemia [CLL], Hodgkin lymphoma, or non-Hodgkin lymphoma [NHL]), 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.
Chronic lymphocytic leukemia: Oral:
Chronic lymphocytic leukemia in previously untreated patients (off-label dosing): 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 (Eichhorst 2009) or 0.5 mg/kg on days 1 and 15 every 28 days for 6 cycles (Goede 2014) or 30 mg/m2 day 1 every 2 weeks (in combination with prednisone) (Raphael 1991) or 40 mg/m2 day 1 every 4 weeks until disease progression or complete remission or response plateau for up to a maximum of 12 cycles (Rai 2000).
Chronic lymphocytic leukemia in previously untreated patients (off-label combinations):
Chlorambucil-obinutuzumab: 0.5 mg/kg on days 1 and 15 every 28 days for 6 cycles (Goede 2014).
Chlorambucil-ofatumumab: 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 (Hillmen 2015).
Chlorambucil-rituximab: 10 mg/m2 once daily for 7 days (days 1 to 7) every 28 days for 6 to 12 cycles (Hillmen 2014).
Manufacturer’s labeling: 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).
Hodgkin lymphoma: Oral: ChlVPP regimen: 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 (Selby 1990) or 6 mg/m2 once daily on days 1 to 14 every 28 days (in combination with vinblastine, procarbazine, and prednisone) for 6 cycles (Vose 1991).
Idiopathic membranous nephropathy (alternative agent) (off-label use): Oral: 0.15 to 0.2 mg/kg/day during months 2, 4, and 6 (alternating with prednisolone/methylprednisolone during months 1, 3, and 5) (Howman 2013; KDIGO 2012). Note: Due to potential adverse events, other agents may be preferred over chlorambucil.
Necrobiotic xanthogranuloma (off-label use; based on limited data): Oral: 2 to 4 mg once daily either with or without systemic corticosteroids (Finan 1986; Hilal 2018; Mehregan 1992; Miguel 2017) or 10 mg once daily for 14 days of a 28-day treatment cycle for 8 cycles (Ryan 2012) or 10 mg once daily, reduced to 2 mg once daily (in combination with prednisone) (Wells 2004).
Non-Hodgkin lymphomas: Oral:
Follicular lymphoma (off-label dosing): 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) (Martinelli 2003; Martinelli 2015).
Mucosa-associated lymphoid tissue lymphoma (off-label dosing): 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) (Zucca 2017).
Manufacturer’s labeling: 0.1 mg/kg/day for 3 to 6 weeks.
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 (Leblond 2013) or 0.1 mg/kg/day (continuously) for at least 6 months (Kyle 2000) or 0.3 mg/kg/day for 7 days every 6 weeks for at least 6 months (Kyle 2000).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal elimination of unchanged chlorambucil and active metabolite (phenylacetic acid mustard) is minimal and renal 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.
Idiopathic membranous nephropathy (off-label use): Serum creatinine >2 mg/dL: Maximum daily dose: 0.1 mg/kg/day (KDIGO 2012).
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).
(For additional information see "Chlorambucil: Pediatric drug information")
Note: For oncologic uses, dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol.
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 (Atra 2002; Capra 2007; Hall 2007; Stoneham 2007)
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) (Baluarte 1978; Hodson 2010; KDIGO 2012); Note: Chlorambucil is not a preferred agent due to a higher incidence of adverse effects with no greater efficacy (Gipson 2009).
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.
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.
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).
Refer to adult dosing. Begin at the lower end of dosing range(s)
The American Society of Clinical Oncology Guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2 (excludes leukemias): Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (ASCO [Griggs 2012]). Note: The manufacturer recommends the maximum dose should not exceed 0.1 mg/kg/day if maintenance therapy is required and with bone marrow infiltration.
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.
Concurrent or within 4 weeks (before or after) of chemotherapy/radiotherapy: Initiate treatment cautiously; reduce dose; monitor closely.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Leukeran: 2 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Leukeran: 2 mg
Oral: May be administered as a single daily dose.
Oral: May be administered as a single daily dose; preferably on an empty stomach.
Hazardous agent (NIOSH 2016 [group 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 2016; USP-NF 2020).
Chronic lymphocytic leukemia: Management of chronic lymphocytic leukemia
Hodgkin lymphoma: Management of Hodgkin lymphoma
Non-Hodgkin lymphoma: Management of non-Hodgkin lymphomas
Idiopathic membranous nephropathy; Necrobiotic xanthogranuloma; Waldenström macroglobulinemia, alternative agent
Chlorambucil may be confused with Chloromycetin
Leukeran may be confused with Alkeran, leucovorin, Leukine, Myleran
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
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
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
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: Chlorambucil may cause severe bone marrow suppression; neutropenia may be severe. Reduce initial dosage if patient has received myelosuppressive or radiation therapy within the previous 4 weeks, or has a depressed baseline leukocyte or platelet count. Irreversible bone marrow damage may occur with total doses approaching 6.5 mg/kg. Progressive lymphopenia may develop (recovery is generally rapid after discontinuation).
• Fertility effects: [US Boxed Warning]: Chlorambucil is probably mutagenic and teratogenic in humans. Chlorambucil produces human infertility.
• Secondary malignancy: [US Boxed Warning]: 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: Have been observed with use; 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; discontinue promptly if skin reaction occurs.
Disease-related concerns:
• Hepatic impairment: Chlorambucil is primarily metabolized in the liver. Dosage reductions should be considered in patients with hepatic impairment.
Other warnings/precautions:
• Vaccines: Avoid administration of live vaccines to immunocompromised patients.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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 diminish the therapeutic effect 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
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect 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
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect 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 diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Absorption is decreased when administered with food. Management: Administer preferably on an empty stomach.
[US Boxed Warning]: Chlorambucil produces human infertility. 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.
Women of childbearing potential should avoid becoming pregnant while receiving treatment.
Following exposure during the first trimester, case reports have noted adverse renal effects (unilateral agenesis) in the newborn.
[US Boxed Warning]: Chlorambucil is probably mutagenic and teratogenic in humans.
It is not known if chlorambucil is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the decision to discontinue chlorambucil or to discontinue breastfeeding should consider the benefits of treatment to the mother.
Monitor LFTs, CBC with differential (weekly, with WBC monitored twice weekly during the first 3 to 6 weeks of treatment). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
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.
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)
Tablets (Leukeran Oral)
2 mg (per each): $31.82
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