FLUDARABINE PHOSPHATE

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. 9%). 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, Fludarabine should be administered up to the achievement of best response (complete or partial remission, usually 6 cycles) and then the drug should be discontinued. Special populations Patients with renal impairment Doses should be adjusted for patients with reduced kidney function.

4). 3). Patients with hepatic impairment No data are available concerning the use of Fludarabine in patients with hepatic impairment. 4). Paediatric population The safety and efficacy of Fludarabine in children below the age of 18 years have not been established.

Therefore, Fludarabine is not recommended for use in children. Elderly Since there are limited data for the use of Fludarabine in older people (>75 years), caution should be exercised with the administration of Fludarabine in these patients.

4). Method of administration Fludarabine should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Fludarabine should only be administered intravenously. No cases have been reported in which paravenously administered Fludarabine led to severe local adverse reactions.

However, unintentional paravenous administration must be avoided. 6.

Summary of safety profile Based on the experience with the use of Fludarabine, the most common adverse events include myelosuppression (neutropenia, thrombocytopenia and anaemia), infection including pneumonia, cough, fever, fatigue, weakness, nausea, vomiting and diarrhoea.

Other commonly reported events include chills, oedema, malaise, peripheral neuropathy, visual disturbance, anorexia, mucositis, stomatitis and skin rash. Serious opportunistic infections have occurred in patients treated with Fludarabine.

Fatalities as a consequence of serious adverse events have been reported. Tabulated list of adverse reactions The table below reports adverse events by MedDRA system organ classes (MedDRA SOCs). The frequencies are based on clinical trial data regardless of the causal relationship with Fludarabine.

The rare adverse reactions were mainly identified from the post-marketing experience. g. 4) Eye disorders Visual disturbances Blindness, System Organ Class Very Common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1000 to <1/100 Rare ≥1/10,000 to <1/1000 Not known optic neuritis, optic neuropathy Cardiac disorders Heart failure, arryhthmia Respiratory, thoracic and mediastinal disorders Cough Pulmonary toxicity (including pulmonary fibrosis, pneumonitis, dyspnoea) Pulmonary Haemorrhage Gastrointestinal disorders Vomiting, diarrhoea, nausea Stomatitis Gastrointestinal haemorrhage, pancreatic enzymes abnormal Hepatobiliary disorders Hepatic enzymes abnormal Skin and subcutaneous tissue disorders Rash Skin cancer, necrolysis epidermal toxic (Lyell type) Stevens- Johnson syndrome Renal and urinary disorder Haemorrhagic cystitis General disorders and administration site conditions Fever, fatigue, weakness Oedema, mucositis, chills, malaise The most appropriate MedDRA term to describe a certain adverse event is listed.

Synonyms or related conditions are not listed, but should be taken into account as well. 1. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

Myelosuppression Severe bone marrow suppression, notably anaemia, thrombocytopenia and neutropenia, has been reported in patients treated with Fludarabine. In a Phase I intravenous study in adult solid tumour patients, the median time to nadir counts was 13 days (range 3 – 25 days) for granulocytes and 16 days (range 2 - 32 days) for platelets.

Most patients had haematologic impairment at baseline either as a result of disease or as a result of prior myelosuppressive therapy. Cumulative myelosuppression may be seen. While chemotherapy-induced myelosuppression is often reversible, administration of fludarabine phosphate requires careful haematologic monitoring.

Fludarabine phosphate is a potent antineoplastic agent with potentially significant toxic side effects. Patients undergoing therapy should be closely observed for signs of haematologic and non-haematologic toxicity. Periodic assessment of peripheral blood counts is recommended to detect the development of anaemia, neutropenia and thrombocytopenia.

Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in adult patients. The duration of clinically significant cytopenia in the reported cases has ranged from approximately 2 months to approximately 1 year.

These episodes have occurred both in previously treated or untreated patients. As with other cytotoxics, caution should be exercised with fludarabine phosphate, when further haematopoietic stem cell sampling is considered. 8) have been reported to occur during or after treatment with fludarabine.

The majority of patients experiencing haemolytic anaemia developed a recurrence in the haemolytic process after rechallenge with fludarabine. Patients treated with fludarabine should be closely monitored for signs of haemolysis. Discontinuation of therapy with fludarabine is recommended in case of haemolysis.

1 − Renal impairment with creatinine clearance < 30 ml/min. − Decompensated haemolytic anaemia. − Lactation.