Leukeran

Leu·ke·ran (lk-rn)

A trademark for the drug chlorambucil.

---

Leukeran,

trademark for an antineoplastic (chlorambucil).

---

chlorambucil Warning - Hazardous drug!

Leukeran

Pharmacologic class: Alkylating agent, nitrogen mustard

Therapeutic class: Antineoplastic, immunosuppressant

Pregnancy risk category D

FDA Boxed 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.

Route	Onset	Peak	Duration
P.O.	Unknown	1 hr	Unknown

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.

---

Leukeran®

Chlorambucil, see there