chlorambucil


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chlorambucil

 [klor-am´bu-sil]
a nitrogen mustardalkylating agent used as an antineoplastic agent.

chlorambucil

Leukeran

Pharmacologic class: Alkylating agent, nitrogen mustard

Therapeutic class: Antineoplastic, immunosuppressant

Pregnancy risk category D

FDA Box Warning

• Drug may suppress bone marrow function severely and is carcinogenic.

• Drug causes infertility and is probably mutagenic and teratogenic.

Action

Interacts with cellular DNA to produce cytotoxic cross-linkage, which disrupts cell function. Cell-cycle-phase nonspecific.

Availability

Tablets: 2 mg

Indications and dosages

Chronic lymphocytic leukemia, malignant lymphoma, Hodgkin's disease

Adults: Initially, 0.1 to 0.2 mg/kg/day P.O. for 3 to 6 weeks as a single dose or in divided doses. Maintenance dosage is based on CBC but shouldn't exceed 0.1 mg/kg/day.

Off-label uses

• Idiopathic membranous nephropathy

• Meningoencephalitis associated with Behçet's disease

• Rheumatoid arthritis

Contraindications

• Hypersensitivity to drug or other alkylating agents

• Pregnancy or breastfeeding

Precautions

Use cautiously in:

• hematopoietic depression, infection, other chronic debilitating diseases

• history of seizures or head trauma

• patients who have undergone radiation or other chemotherapy

• elderly patients

• females of childbearing age

• children (safety and efficacy not established).

Administration

• Before starting therapy, assess for history of seizures or head trauma.

• After full-course radiation or chemotherapy, wait 4 weeks before giving full doses (because of bone marrow vulnerability).

• To minimize GI effects, drug may be given at bedtime with antiemetic, especially if high dosage is prescribed.

Adverse reactions

CNS: peripheral neuropathy, tremor, confusion, agitation, ataxia, flaccid paresis, seizures

EENT: keratitis

GI: nausea, vomiting, diarrhea

GU: sterile cystitis, amenorrhea, sterility, decreased sperm count

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia, bone marrow depression

Hepatic: jaundice, hepatotoxicity

Metabolic: hyperuricemia

Musculoskeletal: muscle twitching

Respiratory: interstitial pneumonitis, pulmonary fibrosis

Skin: rash, erythema multiforme, epidermal necrolysis, Stevens-Johnson syndrome

Other: drug fever, allergic reaction, secondary malignancies

Interactions

Drug-drug. Anticoagulants, aspirin: increased risk of bleeding

Immunosuppressants, myelosuppressants: additive bone marrow depression

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, uric acid: increased levels (may reflect hepatotoxicity)

Granulocytes, hemoglobin, neutrophils, platelets, red blood cells, white blood cells (WBCs): decreased counts

Drug-herbs. Astragalus, echinacea, melatonin: interference with immunosuppressant action

Patient monitoring

Monitor CBC with white cell differential and platelet count weekly.

• Monitor WBC count every 3 to 4 days.

• Assess liver function test results.

Patient teaching

• Instruct patient to immediately report unusual bleeding or bruising, fever, nausea, vomiting, rash, chills, sore throat, cough, shortness of breath, seizures, amenorrhea, unusual lumps or masses, flank or stomach pain, joint pain, lip or mouth sores, or yellowing of skin or sclera.

• Tell patient to take drug with full glass of water.

• Inform patient that drug may increase his risk for infection. Advise him to wash hands frequently, wear a mask in public places, and avoid people with infections.

• Instruct patient to contact prescriber before receiving vaccines.

• Advise female patient to use reliable contraception.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

chlorambucil

(klôr-ăm′byə-sĭl)
n.
An anticancer drug that is a derivitive of nitrogen mustard and is used to depress the proliferation and maturation of lymphocytes in diseases such as leukemia.

chlorambucil

Leukeran Oncology An alkylating chemotherapeutic of the nitrogen mustard family, used for lymphomas and other CAs Adverse effects BM suppression, leukemia, infertility, convulsions

chlorambucil

A nitrogen-mustard drug used in the treatment of LEUKAEMIA and LYMPHOMAS including HODGKIN'S DISEASE. The drug is on the WHO official list. A brand name is Leukeran.

immunosuppressants

Drugs that prevent or reduce the immune response. They are used in the treatment of a variety of severe inflammations such as uveitis, scleritis, keratoconjunctivitis sicca, Behçet's syndrome, sympathetic ophthalmia, and to prevent corneal graft rejection. They include the corticosteroids (e.g. prednisolone), ciclosporin (cyclosporine), tacrolimus, and cytotoxic agents (e.g. azathioprine, chlorambucil, cyclophosphamide, methotrexate). It must be noted that immunosuppressants render the patient more susceptible to infection because immunity is reduced.
References in periodicals archive ?
The primary endpoint is progression-free survival in the Calquence and obinutuzumab arm compared to the chlorambucil and obinutuzumab arm, assessed by an independent review committee, and a key secondary endpoint is IRC-assessed PFS in the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab arm.
A rescue protocol may consist of the same original drugs (in the case above, another round of prednisolone and chlorambucil) or your veterinarian may try a different set of medications.
Label: GAZYVARO in combination with chlorambucil is indicated for the treatment of adult patients with previously untreated CLL and with comorbidities making them unsuitable for full-dose fludarabine based therapy (84).
After consultation with several schools of veterinary medicine and a veterinary oncologist, the owner decided on a regimen of I'm-Yunity (polysaccharopeptide from the Coriolus versicolor mushroom, dose of 100mg/kg/day po), metronomic chlorambucil 1.0 mg po QD (2.0 mg/[m.sup.2]), high doses (900 mg) po QD of omega-3 fatty acids, and Yunnan Baiyao 250 mg po BID for two weeks on, one week off.
In resistant cases cytotoxic agents such as azathioprine, cyclophosphamide and chlorambucil are used in combination with steroids.
However, BR produces fewer complete remissions than FCR.10 In patients with comorbidities and older age, combination of chlorambucil plus an anti-CD20 antibody (rituximab, ofatumumab or obinutuzumab) is considered as standard approach.11, 12
Table 1 Classification of uveitis Type of uveitis Location State of inflammation Anterior Iris Iritis Ciliary body Anterior cyclitis Iris and ciliary body Iridocyclitis Intermediate Vitreous Vitritis Hyalitis Pars planitis Posterior Choroid Choroiditis Retina Retinitis Neuroretinitis Choroid and retina Chorioretinitis Retinochoroiditis Pan-uveitis All of the above All of the above Table 2 Prednisolone acetate 1% Prednisolone sodium phosphate 0.1-0.5% Fluorometholone 0.1% Rimexolone 1% Loteprednol etabonate 0.5% Table 3 Immunosuppressive drugs Table 3 Class Examples Antimetabolites Azathioprine Methotrexate Mycophenolate mofetil Alkylating agents Cyclophosphamide Chlorambucil Antibiotics Cyclosporine Tacromimus Rapamycin Dapsone Adjuvants Bromocriptine Ketoconazole Colchicine
Notably, ibrutinib was associated with a 98% OS rate versus 85% for chlorambucil at 24 months.
He was treated with chlorambucil and remained stable until February 2010 when he developed a chest infection and was found to have a lymphocyte count of 236x[10.sup.9]/L, ANC of 0.9x[10.sup.9]/L, hemoglobin 6g/ dL (DAT negative), and platelets of 71x[10.sup.9]/L.
Professor Chris Fegan, who led trials of the drug at the University of Wales, Cardiff, said: "Gazyvaro shows a significant advantage compared to chlorambucil chemotherapy alone, balancing both efficacy with tolerability.
Gazyva/Gazyvaro is currently approved in more than 40 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukemia.