LEUSTAT Solution for infusion Ref.[8314] Active ingredients: Cladribine

Usual dose

Adults and elderly

HCL

The recommended treatment for Hairy Cell Leukaemia is a single course of LEUSTAT given by continuous intravenous infusion for 7 consecutive days at a dose of 0.09 mg/kg/day (3.6 mg/m²/day). Deviations from this dosage regimen are not advised. Physicians should consider delaying or discontinuing the drug if neurotoxicity or renal toxicity occurs.

CLL

In patients with CLL, the recommended treatment consists of a continuous intravenous infusion of LEUSTAT for 2 hours on days 1 to 5 of a 28 day cycle at a dose of 0.12 mg/kg/day (4.8 mg/m²/day). The patient’s response to therapy should be determined every two cycles of treatment. It is recommended that LEUSTAT Injection be administered in responding patients for 2 cycles after maximum response has occurred, up to a maximum of 6 cycles. Therapy should be discontinued after 2 cycles in non-responding patients. Response for this treatment decision is defined as a lymphocyte reduction of 50% or more, ie if lymphocyte count decreases by 50% or more, administer 2 more cycles and re-evaluate response for decision whether to continue with 2 more cycles up to a maximum of 6 cycles.

Children

Safety and efficacy in children have not been established.

Specific risk factors predisposing to increased toxicity from LEUSTAT 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 aetiology. Patients should be monitored closely for haematological and renal and hepatic toxicity.

Preparation and administration of intravenous solutions

LEUSTAT Injection must be diluted with the designated diluent prior to administration. Since the product does not contain any anti-microbial preservative or bacteriostatic agent, aseptic technique and proper environmental precautions must be observed in preparation of a solution of LEUSTAT. For full details concerning preparation of an infusion solution, see 6.6 Instructions for Use/Handling.

High doses of LEUSTAT have been associated with serious neurological toxicity (including irreversible paraparesis/quadraparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anaemia and thrombocytopenia (See 4.4, Special Warnings and Special Precautions for Use). There is no known specific antidote to overdosage. It is not known whether the drug can be removed from the circulation by dialysis or haemofiltration. Treatment of overdosage consists of discontinuation of LEUSTAT Injection, careful observation and appropriate supportive measures.

Signs and symptoms of overdose may include nausea, vomiting, diarrhoea, severe bone marrow depression (including anaemia, thrombocytopenia, leukopenia, and agranulocytosis), acute renal insufficiency, as well as irreversible neurologic toxicity (paraparesis/quadriparesis), Guillain Barre and Brown Sequard syndromes. Acute, irreversible neuro- and nephrotoxicity have been described in individual patients treated at a dose which was ≥4 times higher than the recommended regimen for hairy cell leukaemia.

No specific antidote exists. Immediate discontinuation of therapy, careful observation, and initiation of appropriate supportive measures (blood transfusions, dialysis, haemofiltration, anti-infectious therapy, etc.) are the indicated treatment of overdose of cladribine. Patients who have received an overdose of cladribine should be monitored haematologically.

The shelf life for LEUSTAT Injection is 2 years.

When stored in refrigerated conditions between 2° to 8°C (36° to 46°F) protected from light, unopened vials of LEUSTAT Injection are stable until the expiration date indicated on the package. Freezing does not adversely affect the solution.

If freezing occurs, thaw naturally to room temperature. DO NOT heat or microwave. Once thawed, the vial of LEUSTAT Injection is stable until expiry if refrigerated. DO NOT REFREEZE.

Once diluted, solutions containing LEUSTAT Injection should be administered promptly or stored in the refrigerator (2° to 8°C) for no more than 8 hours prior to start of administration.

Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light during storage.

LEUSTAT Injection is supplied as a sterile, preservative-free, isotonic solution containing 10 mg (1 mg/ml) of cladribine (as 10 ml) in a single-use, Ph Eur Type I glass 10 ml vial.

Preparation and administration of intravenous solutions: LEUSTAT Injection must be diluted with the designated diluent prior to administration. Since the drug product does not contain any anti-microbial preservative or bacteriostatic agent, aseptic technique and proper environmental precautions must be observed in preparation of a solution of LEUSTAT.

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 LEUSTAT to low temperatures; it may be resolubilised by allowing the solution to warm naturally to room temperature and by shaking vigorously. DO NOT HEAT OR MICROWAVE.

Care must be taken to assure the sterility of prepared solutions. Once diluted, solutions of LEUSTAT Injection 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 LEUSTAT Injection are for single-use only. Any unused portion should be discarded in an appropriate manner.

The potential hazards associated with cytotoxic agents are well established and proper precautions should be taken when handling, preparing, and administering LEUSTAT Injection. The use of disposable gloves and protective garments is recommended. If LEUSTAT Injection contacts the skin or mucous membranes, wash the involved surface immediately with copious amounts of water.

Preparation of a Single Daily Dose

HCL: Add the calculated dose for a 24 hour period (0.09 mg/kg or 0.09 ml/kg or 3.6 mg/m²) of LEUSTAT Injection to an infusion bag containing 100 ml to 500 ml of 0.9% sodium chloride injection (PhEur). Infuse intravenously continuously over 24 hours. Repeat daily for a total of 7 consecutive days.

CLL: Add the calculated dose for a 2 hour period (0.12 mg/kg or 4.8 mg/m²) of LEUSTAT Injection to an infusion bag containing 100 ml to 500 ml of 0.9% sodium chloride injection (PhEur). Infuse intravenously continuously over 2 hours. Repeat daily for a total of 5 consecutive days.

The use of 5% dextrose as a diluent is not recommended because of increased degradation of cladribine. Admixtures of LEUSTAT Injection are chemically and physically stable for at least 24 hours at room temperature under normal room fluorescent light in most commonly available PVC infusion containers.