Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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4-{4-[bis(2-chloroethyl)amino]phenyl}butyric acid; CAS number 305-03-3

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Chlorambucil is a cytostatically active drug, oral, bifunctionally alkylating nitrogen-lost derivative with the molecular formula C14H19Cl2NO2, which is mainly used for the treatment of chronic lymphatic leukaemia and non-Hodgkin's lymphomas (also in Waldenström's disease).

Chlorambucil belongs to a family of alkylants derived from the nitrogen lots. This group of substances includes a number of chlorinated organic nitrogenous compounds in which 2 or 3 H-atoms of ammonia are replaced by β-chloroethyl radicals. The nitrogen-lost derivatives are chemically derivable from the bis(β-chloroethyl)-sulfide (Lost) and have a strong alkylating effect due to the participation of neighbouring groups of the N-atom. Like cyclophosphamide, chlorambucil is a prodrug that acts as an indirect alkylant and is only transformed into a reactive compound during the biotransformation process. Chlorambucil causes intra- and interstrand cross-linking of the DNA as Ankylan.

Spectrum of action
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Chlorambucil has a cytostatic and immunosuppressive effect. Like the other alkylants, chlorambucil does not have a cycle-specific effect, but has a particular effect on cells that are in the G1 or S phase of the cell cycle. The cytostatic effect is therefore particularly noticeable during DNA synthesis, i.e. replication. In addition to inhibiting DNA replication, chlorambucil induces apoptosis in cells by accumulating p53 in the cytosol and subsequently activating an apoptosis activator (Bax). This inhibits cell proliferation and the formation of new malignant cells. The cytotoxic effect of chlorambucil is due both to chlorambucil and its main metabolite, phenylacetic acid solute.

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C85.9 Non-Hodgkin's lymphoma, not specified

C88.00 Macroglobulinemia Waldenström: Without indication of complete remission

C91.10 Chronic lymphocytic leukaemia of the B-cell type [CLL]: No indication of complete remission

Pregnancy/nursing period
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Pregnancy: Chlorambucil has an anti-inflammatory effect and can affect the development of an embryo. Chlorambucil should not be used during pregnancy, especially not during the first trimester.

Dosage and method of use
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As monotherapy, chlorambucil is given as a single dose every 14 days. The initial dosage is 0.4 mg/kg body weight; it is gradually increased by 0.1 mg/kg body weight from the 2nd treatment course until the onset of action or the occurrence of toxic effects.

In combination with prednisone, the initial dose of chlorambucil is 5 mg/m² on days 1 to 3; the treatment cycle is repeated every 14 days.

Low malignant non-Hodgkin lymphomas In combination with prednisone, chlorambucil is given as a single dose every 14 days. The initial dose is 0.4 mg/kg body weight; it is gradually increased by 0.1 mg/kg body weight from the 2nd treatment course until the onset of action or the occurrence of toxic effects.

For further dosages see professional recommendations

Undesirable effects
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Note: Below is a list of side effects by system organ class (see MedDRA below) and absolute frequency. The frequencies are defined as follows: very frequent (≥ 1/10), frequent (≥ 1/100, < 1/10), occasional (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (≤ 1/10,000) not known.

Benign, malignant and unspecific neoplasms (including cysts and polyps)

  • Common: Acute secondary haematological malignancies (especially leukaemias and myelodysplastic syndrome), especially after long-term treatment

Diseases of the blood and lymphatic system:

  • Very often leukopenia, neutropenia, thrombocytopenia, pancytopenia or bone marrow depression (Although bone marrow depression is very common, it is usually reversible if chlorambucil is stopped early enough.
  • Common: Anemia
  • Very rare Irreversible bone marrow failure

Diseases of the immune system

  • Rarely hypersensitivity such as urticaria and angioneurotic edema at the beginning or during the course of treatment. (See also chlorambucil, cutaneous side effects)
  • Angioedema

Diseases of the nervous system:

  • Common: convulsions in children and adolescents with a nephrotic syndrome
  • Rare: convulsions, partial and/or generalized; in children and adolescents
  • and adults receiving normal therapeutic daily doses of chlorambucil or high-dose therapy with chlorambucil
  • Very rarely Movement disorders not associated with convulsions, including tremor, muscle twitching and myoclonus. Peripheral neuropathy

Diseases of the respiratory tract, chest and mediastinum


  • Interstitial pulmonary fibrosis
  • interstitial pneumonia
  • Severe interstitial pulmonary fibrosis has occasionally been observed in patients with chronic lymphocytic leukemia after long-term treatment. Pulmonary fibrosis may regress after discontinuing chlorambucil.

Diseases of the gastrointestinal tract:

Commonly gastrointestinal diseases, such as:

  • Nausea and vomiting
  • Diarrhoea
  • ulceration of the oral mucosa

Liver and bile diseases:


  • Hepatotoxicity
  • Icterus

Diseases of the skin and subcutaneous cell tissue


  • Exantheme


  • Stevens-Johnson syndrome
  • Toxic epidermal necrolysis (see below chlorambucil, cutaneous side effects).

Diseases of the kidneys and urinary tract:

Very rare:

  • Sterile cystitis

Diseases of the reproductive organs and the mammary gland


  • Amenorrhoea
  • Azoospermia

General illnesses and complaints at the place of administration


  • Pyrexia

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Immunization of immunocompromised patients with live vaccines is not recommended.

Purine nucleoside analogues (e.g. fludarabine, pentostatin and cladribine) enhance the cytotoxic effect of chlorambucil ex vivo; however, the clinical significance of this finding is not known.

Simultaneous exposure to X-rays may enhance the effect of chlorambucil on the bone marrow.

From animal experiments it can be concluded that simultaneous administration of phenylbutazone-containing drugs increases the side effects of chlorambucil. Therefore a reduced dose of Chlorambucil is recommended.

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Lost is an abbreviation of the names of the developers Lommel and Steinkopf.


Last updated on: 29.10.2020