Cladribine (Page 4 of 5)

Postmarketing Experience ​

The following additional adverse reactions have been reported since the drug became commercially available. These adverse reactions have been reported primarily in patients who received multiple courses of cladribine injection:

Infections and infestations: Septic shock. Opportunistic infections have occurred in the acute phase of treatment.

Blood and lymphatic system disorders: Bone marrow suppression with prolonged pancytopenia, including some reports of aplastic anemia; hemolytic anemia (including autoimmune hemolytic anemia), which was reported in patients with lymphoid malignancies, occurring within the first few weeks following treatment. Rare cases of myelodysplastic syndrome have been reported.

Immune system disorders: Hypersensitivity.

Metabolism and nutrition disorders: Tumor lysis syndrome.

Psychiatric disorders: Confusion (including disorientation).

Hepatobiliary disorders: Reversible, generally mild increases in bilirubin (uncommon) and transaminases.

Nervous System disorders: Depressed level of consciousness, neurological toxicity (including peripheral sensory neuropathy, motor neuropathy (paralysis), polyneuropathy, paraparesis); however, severe neurotoxicity has been reported rarely following treatment with standard cladribine dosing regimens.

Eye disorders: Conjunctivitis.

Respiratory, thoracic and mediastinal disorders: Pulmonary interstitial infiltrates (including lung infiltration, interstitial lung disease, pneumonitis and pulmonary fibrosis); in most cases, an infectious etiology was identified.

Skin and tissue disorders: Urticaria, hypereosinophilia; Stevens-Johnson. In isolated cases toxic epidermal necrolysis has been reported in patients who were receiving or had recently been treated with other medications (e.g., allopurinol or antibiotics) known to cause these syndromes.

Renal and urinary disorders: Renal failure (including renal failure acute, renal impairment).

OVERDOSAGE

High doses of cladribine have been associated with: irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia (see WARNINGS). There is no known specific antidote to overdosage. Treatment of overdosage consists of discontinuation of cladribine, careful observation and appropriate supportive measures. It is not known whether the drug can be removed from the circulation by dialysis or hemofiltration.

When used in other clinical settings the following ADRs were reported: bacteremia, cellulitis, localized infection, pneumonia, anemia, thrombocytopenia (with bleeding or petechiae), phlebitis, purpura, crepitations, localized edema and edema.

For a description of adverse reactions associated with use of high doses in non-Hairy Cell Leukemia patients, see WARNINGS.

DOSAGE AND ADMINISTRATION

Usual Dose

The recommended dose and schedule of cladribine for active Hairy Cell Leukemia is as a single course given by continuous infusion for 7 consecutive days at a dose of 0.09 mg/kg/day. Deviations from this dosage regimen are not advised. If the patient does not respond to the initial course of cladribine for Hairy Cell Leukemia, it is unlikely that they will benefit from additional courses. Physicians should consider delaying or discontinuing the drug if neurotoxicity or renal toxicity occurs (see WARNINGS).

Specific risk factors predisposing to increased toxicity from cladribine have not been defined. In view of the known toxicities of agents of this class, it would be prudent to proceed carefully in patients with known or suspected renal insufficiency or severe bone marrow impairment of any etiology. Patients should be monitored closely for hematologic and non-hematologic toxicity (see WARNINGS and PRECAUTIONS).

Preparation and Administration of Intravenous Solutions

Cladribine must be diluted with the designated diluent prior to administration. Since the drug product does not contain any antimicrobial preservative or bacteriostatic agent, aseptic technique and proper environmental precautions must be observed in preparation of cladribine solutions.

To prepare a single daily dose

Cladribine injection should be passed through a sterile 0.22µm disposable hydrophilic syringe filter prior to introduction into the infusion bag, prior to each daily infusion. Add the calculated dose (0.09 mg/kg or 0.09 mL/kg) of cladribine through a sterile filter to an infusion bag containing 500 mL of 0.9% Sodium Chloride Injection. Infuse continuously over 24 hours. Repeat daily for a total of 7 consecutive days. The use of 5% dextrose as a diluent is not recommended because of increased degradation of cladribine. Admixtures of cladribine are chemically and physically stable for at least 24 hours at room temperature under normal room fluorescent light in Baxter Viaflex®† PVC infusion containers. Since limited compatibility data are available, adherence to the recommended diluents and infusion systems is advised.

Dose of Cladribine Injection

Recommended Diluent

Quantity of Diluent

24 hour infusion method

1 (day) x 0.09 mg/kg

0.9% Sodium Chloride Injection

500 mL

To prepare a 7 day infusion

The 7 day infusion solution should only be prepared with Bacteriostatic 0.9% Sodium Chloride Injection (0.9% benzyl alcohol preserved). In order to minimize the risk of microbial contamination, both cladribine injection and the diluent should be passed through a sterile 0.22µm disposable hydrophilic syringe filter as each solution is being introduced into the infusion reservoir. First add the calculated dose of cladribine (7 days x 0.09 mg/kg or mL/kg) to the infusion reservoir through the sterile filter.

Then add a calculated amount of Bacteriostatic 0.9% Sodium Chloride Injection (0.9% benzyl alcohol preserved) also through the filter to bring the total volume of the solution to 100 mL. After completing solution preparation, clamp off the line, disconnect and discard the filter. Aseptically aspirate air bubbles from the reservoir as necessary using the syringe and a dry second sterile filter or a sterile vent filter assembly. Reclamp the line and discard the syringe and filter assembly. Infuse continuously over 7 days. Solutions prepared with Bacteriostatic Sodium Chloride Injection for individuals weighing more than 85 kg may have reduced preservative effectiveness due to greater dilution of the benzyl alcohol preservative. Admixtures for the 7 day infusion have demonstrated acceptable chemical and physical stability for at least 7 days in the SIMS Deltec MEDICATION CASSETTE™ Reservoir ‡.

Dose of

Cladribine Injection

Recommended Diluent

Quantity of Diluent

7 day infusion method

(use sterile 0.22µm filter when preparing infusion solution)

7 (days) x 0.09 mg/kg

Bacteriostatic 0.9%

Sodium Chloride

Injection

(0.9% benzyl alcohol)

q.s. to 100 mL

Since limited compatibility data are available, adherence to the recommended diluents and infusion systems is advised. Solutions containing cladribine should not be mixed with other intravenous drugs or additives or infused simultaneously via a common intravenous line, since compatibility testing has not been performed. Preparations containing benzyl alcohol should not be used in neonates (see WARNINGS).

Care must be taken to assure the sterility of prepared solutions. Once diluted, solutions of cladribine should be administered promptly or stored in the refrigerator (2° to 8° C) for no more than 8 hours prior to start of administration. Vials of cladribine are for single-use only. Any unused portion should be discarded in an appropriate manner (see Handling and Disposal ).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. A precipitate may occur during the exposure of cladribine to low temperatures; it may be resolubilized by allowing the solution to warm naturally to room temperature and by shaking vigorously. DO NOT HEAT OR MICROWAVE.

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