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Chlorambucil (Systemic)


VA CLASSIFICATION
Primary: AN100
Secondary: IM403

Commonly used brand name(s): Leukeran.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

immunosuppressant—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Leukemia, chronic lymphocytic (treatment)—Chlorambucil is indicated for palliative treatment of chronic lymphocytic leukemia {01}.

Lymphomas, Hodgkin's (treatment) or
Lymphomas, non-Hodgkin's (treatment)—Chlorambucil is indicated for palliative treatment of Hodgkin's disease and other malignant lymphomas including lymphosarcoma and giant follicular lymphoma {01}.

[Carcinoma, ovarian, epithelial (treatment) ]1—Chlorambucil is indicated for the treatment of epithelial ovarian carcinoma {02} {08}.

[Lymphomas, cutaneous T-cell (treatment) ]1—Chlorambucil is indicated for the treatment of cutaneous T-cell lymphomas {03} {08}.

[Tumors, trophoblastic, gestational (treatment)]1—Chlorambucil is indicated for the treatment of trophoblastic gestational tumors {05} {08}.

[Waldenström's macroglobulinemia (treatment)]1—Chlorambucil is indicated for the treatment of Waldenström's macroglobulinemia {04} {08}.

[Leukemia, hairy cell (treatment) ]1—Chlorambucil is indicated for the treatment of hairy cell leukemia {02}.

[Nephrotic syndrome (treatment)]1—Chlorambucil has been used as an immunosuppressant, in combination with prednisone, in the treatment of steroid-resistant or frequently relapsing steroid-sensitive minimal-change nephrotic syndrome in children and adults, although there are significant risks associated with its use. The most common dose-limiting short-term toxicity is bone marrow depression. Because of potential long-term toxicity (male sterility, leukemia), use of chlorambucil is recommended only for patients unresponsive to or seriously intolerant of steroid treatment.

[Histiocytosis X (treatment)]1—Chlorambucil is indicated as reasonable medical therapy at some point in the management of Histiocytosis X (Letterer-Siwe disease).{09}

Extreme caution is recommended in use of chlorambucil for non-neoplastic conditions because of potential carcinogenicity with long-term use of this agent.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    304.22

pKa—
    5.8

Mechanism of action/Effect:

Chlorambucil is a bifunctional alkylating agent of the nitrogen mustard type {01}. Chlorambucil is cell cycle–phase nonspecific, although it is also cytotoxic to nonproliferating cells. Activity occurs as a result of formation of an unstable ethylenimmonium ion, which alkylates or binds with many intracellular molecular structures, including nucleic acids. Its cytotoxic action is primarily due to cross-linking of strands of DNA, which inhibits nucleic acid synthesis {06} {07}.


Other actions/effects:

Also has immunosuppressant activity.

Absorption:

Rapidly and completely absorbed from the gastrointestinal tract {01}.

Protein binding:

Very high (99%), specifically to albumin {01} {06}.

Biotransformation:

Hepatic, extensive and rapid {01}. The primary metabolite, phenylacetic acid mustard {01} (an aminophenyl acetic acid derivative), is active. Also undergoes spontaneous degradation, forming monohydroxy and dihydroxy derivatives {01} {06}.

Half-life:

Chlorambucil—Approximately 1.5 hours {01}.

Aminophenyl acetic acid derivative metabolite—2.4 hours {01} {06}.

Time to peak plasma concentration

1 hour {01}.

Elimination:
    Renal, less than 1% as chlorambucil or phenylacetic acid mustard {01}.
    In dialysis—Not dialyzable {01}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other alkylating agents (i.e., those who experience skin rash) may also be sensitive to chlorambucil {01}.

Carcinogenicity

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effect of dose and duration of therapy is also unknown, although risk seems to increase with long-term use. Although information is limited, available data seem to indicate that the carcinogenic risk is greatest with the alkylating agents.

Chlorambucil has been shown to be carcinogenic in mice {01}and in humans {10}. There are many reports of acute leukemia occurring in patients treated with chlorambucil for both malignant and nonmalignant diseases {01}, often in combination with radiation or other chemotherapy {01} {06}. Risk appears to be related to cumulative dose and duration of therapy, but a threshold cumulative dose has not been defined {01} {06}.

Mutagenicity

Chlorambucil has been shown to cause chromatid or chromosome damage in humans {01} {06}.

Pregnancy/Reproduction
Fertility—
Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking antineoplastic therapy, especially with the alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.

However, there have been numerous reports of prolonged or permanent azoospermia and permanent sterility with long-term use of chlorambucil, especially in prepubertal and pubertal males. Amenorrhea has been reported in pubertal and adult females; autopsy studies of ovaries from women treated with combination therapy including chlorambucil have shown varying degrees of fibrosis, vasculitis, and depletion of primordial follicles. {01} {06}Infertility has been observed when chlorambucil was employed in the therapy of malignant and non-malignant diseases.{10}

Pregnancy—
Adequate and well-controlled studies in humans have not been done {01} {06}. Although several successful pregnancies have been reported with chlorambucil use, two cases of an infant with an absent kidney and ureter have also been reported {01} {06}.

First trimester: It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered.

Other hazards to the fetus include adverse reactions seen in adults.

In general, use of a contraceptive is recommended during cytotoxic drug therapy.

In rats, urogenital malformations including absence of a kidney have been reported {01} {06}.

FDA Pregnancy Category D {01} {06}.

Breast-feeding

Although very little information is available regarding distribution of antineoplastic agents into breast milk, breast-feeding is not recommended during chemotherapy because of the risks to the infant (adverse effects, mutagenicity, carcinogenicity). It is not known whether chlorambucil is distributed into breast milk {01} {06}.

Pediatrics

Appropriate studies performed to date generally have not demonstrated pediatrics-specific problems that would limit the usefulness of chlorambucil in children. However, children taking chlorambucil for nephrotic syndrome are reported to have an increased risk of seizures {01} {06}.


Geriatrics


No information is available on the relationship of age to the effects of chlorambucil in geriatric patients.


Dental

The bone marrow depressant effects of chlorambucil may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Chlorambucil may also infrequently cause stomatitis, which is associated with considerable discomfort {06}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Allopurinol or
Colchicine or
» Probenecid or
» Sulfinpyrazone    (chlorambucil may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse chlorambucil-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents)


Antidepressants, tricyclic or
Bupropion or
Clozapine or
Haloperidol or
Loxapine or
Maprotiline or
Molindone or
Monoamine oxidase (MAO) inhibitors, including furazolidone and procarbazine or
Phenothiazines or
Pimozide or
Thioxanthenes    (these medications may lower the seizure threshold and increase the risk of chlorambucil-induced seizures {01})


Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of chlorambucil may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of chlorambucil, if necessary, should be based on blood counts)


» Bone marrow depressants, other (see Appendix II ) or
» Radiation therapy    (additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


» Immunosuppressants, other, such as:
Azathioprine
Corticosteroids, glucocorticoid
Corticotropin (ACTH)
Cyclophosphamide
Cyclosporine
Cytarabine
Mercaptopurine
Muromonab-CD3
Tacrolimus    (concurrent use with chlorambucil may increase the risk of infection and development of neoplasms)


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by chlorambucil therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by chlorambucil therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the chlorambucil therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alkaline phosphatase and
Aspartate aminotransferase (AST [SGOT])    (values may rarely be increased, indicating hepatotoxicity)


Uric acid    (concentrations in blood and urine may be increased)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medicine should not be used when the following medical problems exist:
» Hypersensitivity to chlorambucil and to other alkylating agents{10}
» Prior resistance to chlorambucil{10}
Risk-benefit should be considered when the following medical problems exist
» Bone marrow depression
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


Gout, history of or
Urate renal stones, history of    (risk of hyperuricemia)


Head trauma or
Seizure disorder, history of    (increased risk of seizures {01})


» Infection
» Tumor cell infiltration of bone marrow
» Caution should be used also in patients who have had previous cytotoxic drug therapy or radiation therapy.

Patient monitoring
The following are especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Alanine aminotransferase (ALT [SGPT]) values and
Alkaline phosphatase values and
Aspartate aminotransferase (AST [SGOT]) values and
Lactate dehydrogenase (LDH) values    (recommended prior to initiation of therapy and at frequent {01} intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


» Hematocrit or hemoglobin and
» Leukocyte count, total and, if appropriate, differential and
» Platelet count    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Uric acid concentrations, serum    (recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)




Side/Adverse Effects

Note: Many “side effects” of antineoplastic therapy are unavoidable and represent the medication's pharmacologic action. Some of these (for example, leukopenia and thrombocytopenia) are actually used as parameters to aid in individual dosage titration.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
—dose-related     
Lymphopenia {01} , leukopenia, neutropenia, immunosuppression, or infection (fever or chills; cough or hoarseness ; lower back or side pain; painful or difficult urination)—usually asymptomatic
    
thrombocytopenia (unusual bleeding or bruising; black, tarry stools ; blood in urine or stools; pinpoint red spots on skin)—usually asymptomatic

Note: With a short course of therapy, leukopenia and thrombocytopenia may not occur until the third week of treatment and usually persist for 1 to 2 weeks (or sometimes up to 3 to 4 weeks) after withdrawal of chlorambucil. The neutrophil count may continue to decrease for up to 10 days after the last dose. After a single high dose of chlorambucil, the nadir of the leukocyte and platelet counts occurs after 7 to 14 days, with recovery in 2 to 3 weeks.
In general, short intermittent courses are thought to cause less risk of serious bone marrow depression than continuous therapy, by allowing bone marrow regeneration between courses. Excessive doses or prolonged therapy (a total dose of 6.5 mg per kg of body weight [mg/kg] in a single course) may result in pancytopenia and irreversible bone marrow damage {06}.


Incidence less frequent
    
Allergic reaction (skin rash)
    
angioneurotic edema{10} (large, swollen hives ; itching )
    
hyperuricemia or uric acid nephropathy (joint pain; lower back or side pain; swelling of feet or lower legs)
    
stomatitis {01} (sores in mouth and on lips)
    
urticaria{10} (itching; hives)

Note: Skin rash has been reported to progress rarely to erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome {01}.
Note:  Urticaria and angioneurotic edema have been reported following initial or subsequent dosing{10}.


Hyperuricemia or uric acid nephropathy occurs most commonly during initial treatment of patients with leukemia or lymphoma, as a result of rapid cell breakdown that leads to elevated serum uric acid concentrations.
Stomatitis may be associated with neutropenia.


Incidence rare
    
Drug fever {01}
    
hepatotoxicity, hepatic necrosis, or cirrhosis ( yellow eyes or skin)
    
myoclonia{10} (muscle twitching or jerking; rhythmic movement of muscles)
    
neurotoxicity {01} (agitation; confusion; hallucinations ; seizures; severe weakness or paralysis ; tremors; trouble in walking)
    
pulmonary fibrosis (cough; shortness of breath)—occurs after long-term use
    
skin reactions, severe, including erythema multiforme, epidermal necrolysis, and Stevens-Johnson syndrome {01} (blisters on skin ; severe skin rash; sores in mouth; fever may also be associated with Stevens-Johnson syndrome)

Note: Rare, focal and/or generalized seizures have been reported in both children and adults at therapeutic daily doses, and in pulse dosing regimens and acute overdose {01}. However, the risk may be increased in children with nephrotic syndrome (seizures may occur 6 to 90 days after initiation of treatment) and in patients receiving high pulse doses {01}. Neurotoxicity is usually reversible on withdrawal of chlorambucil {01}.
Pulmonary fibrosis is usually reversible after chlorambucil is withdrawn, but fatalities have been reported.




Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
    
Changes in menstrual period
    
dermatitis (itching of skin )
    
nausea and vomiting

Note: Nausea and vomiting are associated with single oral doses of 20 mg or more {01}, usually last less than 24 hours, and become less frequent with continued therapy; may persist up to 7 days after a single high dose.




Those indicating need for medical attention if they occur after medication is discontinued
    
Bone marrow damage, possibly irreversible (fever or chills ; cough or hoarseness; lower back or side pain; painful or difficult urination; unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)
    
pulmonary toxicity (cough; shortness of breath)




Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Symptoms of overdose, in order of frequency
    
Pancytopenia, reversible (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination; unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)
    
neurotoxicity, including ataxia{01} (trouble in walking), agitation
and seizures


Treatment of overdose
To enhance elimination—Immediate evacuation of the stomach.

Monitoring—Monitoring of blood counts at least three times a week for at least 3 weeks or until bone marrow function has recovered {01}.

Supportive care—Supportive, symptomatic treatment. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Chlorambucil (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to chlorambucil or other alkylating agents

Pregnancy—Use not recommended because of mutagenic, teratogenic, and carcinogenic potential; advisability of using contraception; telling physician immediately if pregnancy is suspected





Breast-feeding—Not recommended because of risk of serious side effects
Other medications, especially probenecid, sulfinpyrazone, other bone marrow depressants, other immunosuppressants, or previous cytotoxic drug or radiation therapy
Other medical problems, especially prior resistance to chlorambucil, bone marrow depression, chickenpox, herpes zoster, or infection.

Proper use of this medication
» Importance of not taking more or less medication than the amount prescribed

Caution in taking combination therapy; taking each medication at the right time

Importance of ample fluid intake and subsequent increase in urine output to aid in excretion of uric acid

» Possible nausea and vomiting; importance of continuing medication despite stomach upset

Checking with physician if vomiting occurs shortly after dose is taken

» Proper dosing
Missed dose: If dosing schedule is—

• Once a day: Taking as soon as possible if remembered same day; if not remembered until next day, skipping missed dose and taking next regularly scheduled dose


• Several times a day: Taking as soon as possible; however, if almost time for next dose, not taking missed dose; not doubling doses


» Proper storage

Precautions while using this medication
» Importance of close monitoring by the physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury might occur


Side/adverse effects
May cause adverse effects such as blood problems and cancer

Signs of potential side effects, especially angioneurotic edema, lymphopenia, leukopenia, myoclonia, neutropenia, immunosuppression, infection, thrombocytopenia, allergic reaction, hyperuricemia, uric acid nephropathy, stomatitis, drug fever, hepatotoxicity, hepatic necrosis, cirrhosis, neurotoxicity, pulmonary fibrosis, urticaria, and severe skin reactions

Physician or nurse can help in dealing with side effects


General Dosing Information
Patients receiving chlorambucil should be under supervision of a physician experienced in use of alkylating agents.

A variety of dosage schedules and regimens of chlorambucil, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature as well as the manufacturer's literature in choosing a specific dosage.

Dosage must be adjusted to meet the individual requirements of each patient, based on clinical response and degree of bone marrow depression.

Development of uric acid nephropathy in patients with leukemia or lymphoma may be prevented by adequate oral hydration and, in some cases, administration of allopurinol. Alkalinization of urine may be necessary if serum uric acid concentrations are elevated.

It is recommended that chlorambucil be withdrawn if signs of pulmonary toxicity or a severe skin reaction {01} occurs.

Because of the risk of enhanced bone marrow toxicity, use of chlorambucil is not recommended within 4 to 6 weeks of radiation therapy or chemotherapy with drugs that depress bone marrow function.

Because the decrease in neutrophil count may continue for 10 days after the last dose of chlorambucil, caution is necessary as the total dose approaches 6.5 mg per kg of body weight (mg/kg) because of the risk of pancytopenia {01}.

If the white blood cell count (particularly granulocyte count) falls suddenly, a reduction in dosage or withdrawal of therapy plus continued monitoring is required until leukocyte and platelet levels become adequate. Persistence of low neutrophil and platelet counts or presence of peripheral lymphocytosis may indicate bone marrow infiltration; if that is confirmed by bone marrow examination, the daily dosage of chlorambucil should not exceed 100 mcg (0.1 mg) per kg of body weight {01}.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of chlorambucil. These may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using caution to prevent falls and other injuries. Such patients should avoid alcohol and aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In neutropenic patients who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.


Combination chemotherapy
Although chlorambucil is usually used alone, it may be used in combination with other agents in various regimens. As a result, incidence and/or severity of side effects may be altered and different dosages (usually reduced) may be used. For example, chlorambucil is part of the following chemotherapeutic combination (a commonly used acronym is in parentheses):    —chlorambucil and prednisone (CHL + PRED).
For specific dosages and schedules, consult the literature. For information regarding each agent, consult the individual monographs.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

CHLORAMBUCIL TABLETS USP

Usual adult dose
Leukemia, chronic lymphocytic or
Lymphomas, Hodgkin's or
Lymphomas, non-Hodgkin's
Initiation or short course: Oral, 100 to 200 mcg (0.1 to 0.2 mg) per kg of body weight a day or 3 to 6 mg per square meter of body surface area, usually 4 to 10 mg, a day, as a single dose or in divided doses, for three to six weeks {06}.

Note: An intermittent, biweekly, or once-monthly pulse course of therapy may produce less hematologic toxicity; an initial dose of 400 mcg (0.4 mg) per kg of body weight or 12 mg per square meter of body surface area is increased by 100 mcg (0.1 mg) per kg of body weight or 3 mg per square meter of body surface area until an effective or toxic dose is reached, then adjusted as necessary.


[Nephrotic syndrome]1
Oral, 100 to 200 mcg (0.1 to 0.2 mg) per kg of body weight per day, in a single dose, for eight to twelve weeks.

Note: The maximum recommended cumulative dose is 14 mg per kg of body weight or a maximum duration of treatment of 12 weeks; some clinicians recommend a maximum cumulative dose of 8.2 mg per kg of body weight or a maximum of 6 weeks of treatment.


[Histiocytosis X]1
Studies have shown that adults have benefited from treatment with oral chlorambucil, at a dosage of 5 mg per squared meter of body surface area per day, for a treatment duration determined by patient response.{09}


Usual adult prescribing limits
Presence of lymphocytic infiltration of bone marrow or hypoplastic bone marrow—Up to 100 mcg (0.1 mg) per kg of body weight per day {01}.

Usual pediatric dose
Leukemia, chronic lymphocytic or
Lymphomas, Hodgkin's or
Lymphomas, non-Hodgkin's
Oral, 100 to 200 mcg (0.1 to 0.2 mg) per kg of body weight or 4.5 mg per square meter of body surface area a day, as a single dose or in divided daily doses.

[Nephrotic syndrome]1
See Usual adult dose.

[Histiocytosis X]1
Studies have shown that children older than 1 month of age have benefited from treatment with oral chlorambucil, at a dosage of 5 mg per squared meter of body surface area per day, for a treatment duration determined by patient response.{09}


Strength(s) usually available
U.S.—


2 mg (Rx) [Leukeran (lactose) (sucrose )]

Canada—


2 mg (Rx) [Leukeran]

Packaging and storage:
Store in a refrigerator, 2 °C to 8 °C (36 to 46 °F){11}



Developed: 09/02/1999
Revised: 01/08/2003



References
  1. Leukeran package insert (BW—US), Rev 4/86; Rev 9/88; Rev 10/92.
  1. Hematology-Oncology Advisory Panel (1985-1990) Memorandum No. 26, 1989.
  1. Cutaneous T-cell lymphoma. National Cancer Institute. Available from: URL: http://cancernet.nci.nih.gov
  1. Devita VT, Hellman S, Rosenberg SA, editors. Cancer. Principles and practice of oncology. 5th ed. Philadelphia: JB Lippincott Company; 1997. p. 2376.
  1. Gestational trophoblastic tumor. National Cancer Institute. Available from: URL: http://cancernet.nci.nih.gov
  1. Leukeran package insert (Glaxo-Wellcome—US), Rev 8/94, Rec 07/17/97.
  1. Leukeran package insert (Glaxo-Wellcome—Canada), Rev 02/20/97, Rec 03/19/97.
  1. Reviewers' responses to Hematology-Oncology Advisory Panel Memo #9 of 1/30/97.
  1. Reviewers' consensus on the use of chlorambucil for the treatment of Histiocytosis X (Letterer-Siwe disease) evidence table, 6/23/00.
  1. Product Information: Leukeran®, chlorambucil. GlaxoWellcome, Research Triangle Park, N.C., (PI revised 04/2001) reviewed 08/2001.
  1. Product Information: Leukeran®, chlorambucil. Glaxo Smith Kline, Research Triangle Park, N.C., (PI revised 08/2001) reviewed 01/2003.
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