No

Antineoplastic Agent, Antimetabolite

Treatment of hairy cell leukemia (HCL) and chronic lymphocytic leukemias

D

Patients with a prior history of hypersensitivity to cladribine

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Because of its myelosuppressive properties, cladribine should be used with caution in patients with pre-existing hematologic or immunologic abnormalities; prophylactic administration of allopurinol should be considered in patients receiving cladribine because of the potential for hyperuricemia secondary to tumor lysis; appropriate antibiotic therapy should be administered promptly in patients exhibiting signs and symptoms of neutropenia and infection.

>10%:

Bone marrow suppression: Commonly observed in patients treated with cladribine, especially at high doses; at the initiation of treatment, however, most patients in clinical studies had hematologic impairment as a result of HCL. During the first 2 weeks after treatment initiation, mean platelet counts decline and subsequently increased with normalization of mean counts by day 12. Absolute neutrophil counts and hemoglobin declined and subsequently increased with normalization of mean counts by week 5 and week 6. CD4 counts nadir at approximately 270, 4-6 months after treatments. Mean CD4 counts after 15 months were <500/mm³. Patients should be considered immunosuppressed for up to one year after cladribine therapy.

Central nervous system: Fatigue, headache

Fever: Temperature greater than or equal to 101°F has been associated with the use of cladribine in approximately 66% of patients in the first month of therapy. Although 69% of patients developed fevers, <33% of febrile events were associated with documented infection.

Dermatologic: Rash

Gastrointestinal: Nausea and vomiting are not severe with cladribine at any dose level. Most cases of nausea were mild, not accompanied by vomiting and did not require treatment with antiemetics. In patients requiring antiemetics, nausea was easily controlled most often by chlorpromazine.

Local: Injection site reactions

1% to 10%:

Cardiovascular: Edema, tachycardia

Central nervous system: Dizziness, insomnia, pain, chills, malaise

Dermatologic: Pruritus, erythema

Gastrointestinal: Constipation, abdominal pain

Neuromuscular & skeletal: Myalgia, arthralgia, weakness

Miscellaneous: Diaphoresis, trunk pain

Store intact vials under refrigeration (2°C to 8°C); stable for 7 days at room temperature

Further dilution in 100-1000 mL NS is stable for 72 hours. Stable in PVC containers for 24 hours at room temperature and 7 days in Pharmacia Deltec® medication cassettes at room temperature. For 7-day infusion, dilute with bacteriostatic NS and filter through 0.22 m filter prior to addition into infusion reservoir.

Incompatible with D₅W

Standard I.V. 24-hour infusion dilution:

24-hour dose/500 mL NS

24-hour infusion solution is stable for 24 hours at room temperature

Standard I.V. 7-day infusion dilution:

7-day dose/q.s. to 100 mL with bacteriostatic NS

7-day infusion solution is stable for 7 days at room temperature

A purine nucleoside analogue; prodrug which is activated via phosphorylation by deoxycytidine kinase to a 5'-triphosphate derivative. This active form incorporates into susceptible cells and into DNA to result in the breakage of DNA strand and shutdown of DNA synthesis. This also results in a depletion of nicotinamide adenine dinucleotide and adenosine triphosphate (ATP). The induction of strand breaks results in a drop in the cofactor nicotinamide adenine dinucleotide and disruption of cell metabolism. ATP is depleted to deprive cells of an important source of energy. Cladribine effectively kills resting as well as dividing cells.

Distribution: V_d: 4.52±2.82 L/kg

Protein binding: 20% to plasma proteins

Half-life: Biphasic: Alpha: 25 minutes; Beta: 6.7 hours; Terminal, mean (normal renal function): 5.4 hours

Elimination: Mean: 978±422 mL/hour/kg; estimated systemic clearance: 640 mL/hour/kg

I.V.:

Acute leukemia: The safety and effectiveness of cladribine in children have not been established; in a phase I study involving patients 1-21 years of age with relapsed acute leukemia, cladribine was administered by CIV at doses ranging from 3-10.7 mg/m²/day for 5 days (0.5-2 times the dose recommended in HCL). Investigators reported beneficial responses in this study; the dose-limiting toxicity was severe myelosuppression with profound neutropenia and thrombocytopenia.

CIV: 15-18 mg/m²/day for 5 days

Adults:

Hairy cell leukemia:

CIV: 0.09-0.1 mg/kg/day continuous infusion for 7 consecutive days

CIV: 4 mg/m²/day for 7 days

Non-Hodgkin's lymphoma: CIV: 0.1 mg/kg/day for 7 days

May cause drowsiness, dizziness, or insomnia

May cause bone marrow suppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be administered by infusion. Do not use alcohol, aspirin-containing products, and OTC medications without consulting prescriber. It is important to maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition during therapy; frequent small meals may help. You may experience nausea or vomiting (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help). You will be more susceptible to infection (avoid crowds and exposure to infection). You may experience muscle weakness or pain (mild analgesics may help). Frequent mouth care with soft toothbrush or cotton swabs and frequent mouth rinses may help relieve mouth sores. Report rash; fever; chills; unusual bruising or bleeding; signs of infection; excessive fatigue; yellowing of eyes or skin; change in color of urine or stool; swelling, warmth, or pain in extremities; or difficult respirations. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Do not breast-feed until prescriber advises it is safe.

Monitor periodic assessment of peripheral blood counts, particularly during the first 4-8 weeks post-treatment, is recommended to detect the development of anemia, neutropenia, and thrombocytopenia and for early detection of any potential sequelae (ie, infection or bleeding)

Injection, preservative free: 1 mg/mL (10 mL)

Baltz JK and Montello MJ, "Cladribine for the Treatment of Hematologic Malignancies," Clin Pharm, 1993, 12(11):805-13.

Beutler E, "Cladribine (2-Chlorodeoxyadenosine)," Lancet, 1992, 340(8825):952-6.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Kearns CM, Biakley RL, Santane VM, et al, "Pharmacokinetics of Cladribine (2-Chlorodioxyadenosine) in Children with Acute Leukemia," Cancer Research, 1994, 54:1235-39.

Larson RA, et al, "Dose Escalation Trial of Cladribine Using 5 Daily I.V. Infusions in Patients with Advanced Hematologic Malignancies," J Clin Oncol, 1996, 14(1):188-95.

Liliemark J, "The Clinical Pharmacokinetics of Cladribine," Clin Pharmacokinet, 1997, 32(2):120-31.

Piro LD, "2-Chlorodeoxyadenosine Treatment of Lymphoid Malignancies," Blood, 1992, 79(4):843-5.

Saven A and Piro LD, "2-Chlorodeoxyadenosine: A Potent Antimetabolite With Major Activity in the Treatment of Indolent Lymphoproliferative Disorders," Hematol Cell Ther, 1996, 38(Suppl 2):S93-101.

Stine KC, Saylors RL, Williams LL, et al, "2-Chlorodeoxyadenosine (2-CDA) for the Treatment of Refractory or Recurrent Langerhans Cell Histiocytosis (LCH) in Pediatric Patients," Med Pediatr Oncol, 1997, 29:288-92.

Tallman MS and Hakimian D, "Current Results and Prospective Trials of Cladribine in Chronic Lymphocytic Leukemia," Semin Hematol, 1996, 33(Suppl 1):23-7.