FLUDARA Powder for solution for injection or infusion Ref.[8137] Active ingredients: Fludarabine

Posology

The recommended dose is 25 mg fludarabine phosphate/m² body surface area given daily for 5 consecutive days every 28 days by intravenous route. Each vial is to be made up in 2 ml water for injection. Each ml of the resulting solution will contain 25 mg fludarabine phosphate (see section 6.6).

The required dose (calculated on the basis of the patient’s body surface area) of the reconstituted solution is drawn up into a syringe. For intravenous bolus injection this dose is further diluted in 10 ml sodium chloride 9 mg/ml (0.9%). Alternatively, for infusion, the required dose drawn up in a syringe may be diluted in 100 ml sodium chloride 9 mg/ml (0.9%) and infused over approximately 30 minutes.

The duration of treatment depends on the treatment success and the tolerability of the drug.

In CLL patients, Fludara should be administered up to the achievement of best response (complete or partial remission, usually 6 cycles) and then the drug should be discontinued.

Patients with renal impairment

Doses should be adjusted for patients with reduced kidney function. If creatinine clearance is between 30 and 70 ml/min, the dose should be reduced by up to 50% and close haematological monitoring should be used to assess toxicity (see section 4.4).

Fludara treatment is contraindicated, if creatinine clearance is <30 ml/min (see section 4.3).

Patients with hepatic impairment

No data are available concerning the use of Fludara in patients with hepatic impairment. In this group of patients, Fludara should be used with caution.

Paediatric population

The safety and efficacy of Fludara in children below the age of 18 years have not been established. Therefore, Fludara is not recommended for use in children.

Older people

Since there are limited data for the use of Fludara in older people (>75 years), caution should be exercised with the administration of Fludara in these patients.

In patients over the age of 65 years, creatinine clearance should be measured (see “Patients with renal impairment” and section 4.4).

Method of administration

Fludara should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.

It is strongly recommended that Fludara should be only administered intravenously. No cases have been reported in which paravenously administered Fludara led to severe local adverse reactions. However, unintentional paravenous administration must be avoided.

Precautions to be taken before handling the medicinal product

For instructions on handling and reconstitution of the medicinal product before administration, see section 6.6.

High doses of Fludara have been associated with leukoencephalopathy, acute toxic leukoencephalopathy, or reversible posterior leukoencephalopathy syndrome (RPLS). Symptoms may include headache, nausea and vomiting, seizures, visual disturbances such as vision loss, altered sensorium, and focal neurological deficits. Additional effects may include optic neuritis, and papillitis, confusion, somnolence, agitation, paraparesis/quadriparesis, muscle spasticity, incontinence, irreversible central nervous system toxicity characterised by delayed blindness, coma, and death. High doses are also associated with severe thrombocytopenia and neutropenia due to bone marrow suppression.

There is no known specific antidote for Fludara overdosage. Treatment consists of drug discontinuation and supportive therapy.

Unopened vial: 3 years.

Reconstituted and diluted solution: Chemical and physical in-use stability after reconstitution has been demonstrated for 7 days at 4°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should not be longer than 24 hours at 2°C to 8°C or 8 hours at room temperature.

This medicinal product does not require any special storage conditions.

For storage conditions of the reconstituted or diluted medicinal product, see section 6.3.

10 ml colourless Type I glass vials containing 50 mg fludarabine phosphate.

Pack size: 5 vials per carton.

Reconstitution

Fludara should be prepared for parenteral use by aseptically adding sterile water for injection. When reconstituted with 2 ml of sterile water for injection, the powder should fully dissolve in 15 seconds or less. Each ml of the resulting solution will contain 25 mg of fludarabine phosphate, 25 mg of mannitol, and sodium hydroxide (to adjust the pH to 7.7). The pH range for the final product is 7.2-8.2.

Dilution

The required dose (calculated on the basis of the patient’s body surface) is drawn up into a syringe.

For intravenous bolus injection this dose is further diluted in 10 ml sodium chloride 9mg/ml (0.9%). Alternatively, for infusion, the required dose may be diluted in 100 ml sodium chloride 9mg/ml (0.9%) and infused over approximately 30 minutes.

In clinical studies, the product has been diluted in 100 ml or 125 ml of 5% dextrose injection or sodium chloride 9mg/ml (0.9%).

Inspection prior to use

The reconstituted solution is clear and colourless. It should be visually inspected before use.

Only clear and colourless solutions without particles should be used. Fludara should not be used in case of a defective container.

Handling and disposal

Fludara should not be handled by pregnant staff.

Procedures for proper handling should be followed according to local requirements for cytotoxic drugs.

Caution should be exercised in the handling and preparation of the Fludara solution. The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If the solution comes into contact with the skin or mucous membranes, the area should be washed thoroughly with soap and water. In the event of contact with the eyes, rinse them thoroughly with copious amounts of water. Exposure by inhalation should be avoided.

The medicinal product is for single use only. Any unused medicinal product, spillage or waste material should be disposed of in accordance with local requirements.