Fludarabine Tablets Side Effects
Please note - some side effects for Fludarabine Tablets may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Fludarabine Tablets Side Effects - for the Professional
Fludarabine Tablets
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to fludarabine phosphate tablets in 159 patients exposed to the drug. Fludarabine phosphate tablets were studied primarily in Study 1 in 78 patients with CLL who received prior therapy and in Study 2 in 81 patients with CLL who had not received prior therapy.
Based on experience with the intravenous and oral use of fludarabine phosphate, the most common adverse reactions include myelosuppression (neutropenia, thrombocytopenia and anemia), fever and chills, infection, and nausea and vomiting. Other commonly reported events include malaise, fatigue, anorexia, and weakness. Serious opportunistic infections have occurred in patients with CLL treated with fludarabine phosphate. The most frequently reported adverse reactions and those reactions which are more clearly related to the drug, as reported in clinical studies conducted with intravenous and oral fludarabine phosphate, are arranged below according to body system.
Hematopoietic Systems
Hematologic events (neutropenia, thrombocytopenia, and/or anemia) were reported in the majority of patients with CLL treated with fludarabine phosphate. During intravenous fludarabine phosphate treatment of 133 patients with CLL, the absolute neutrophil count decreased to less than 500/mm3 in 59% of patients, hemoglobin decreased from pretreatment values by at least 2 grams percent in 60%, and platelet count decreased from pretreatment values by at least 50% in 55%. Among 78 patients with B-CLL who were treated with oral fludarabine phosphate, the absolute neutrophil count decreased to less than 500/mm3 in 37% of patients, hemoglobin decreased from pretreatment values by at least 2 grams percent in 14%, and platelet count decreased from pretreatment values by at least 50% in 17% of patients. Myelosuppression may be severe, cumulative, and may affect multiple cell lines. Bone marrow fibrosis occurred in one CLL patient treated with fludarabine phosphate intravenously. In the pivotal oral fludarabine phosphate study (Study 1), there was one report of a non-fatal case of pancytopenia. Similarly, there was one case of non-fatal pancytopenia reported among the 133 patients with CLL treated with intravenous fludarabine phosphate.
Life-threatening and sometimes fatal autoimmune hemolytic anemias have been reported to occur in patients receiving fludarabine phosphate. [See Warnings and Precautions (5.2)] The majority of patients rechallenged with fludarabine phosphate developed a recurrence in the hemolytic process.
Metabolic
Tumor lysis syndrome has been reported in patients with CLL treated with fludarabine phosphate for injection. This complication may include hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, hyperkalemia, hematuria, urate crystalluria, and renal failure. The onset of this syndrome may be heralded by flank pain and hematuria.
Nervous System
Objective weakness, agitation, confusion, visual disturbances, and coma have occurred in patients with CLL treated with fludarabine phosphate at the recommended dose. Peripheral neuropathy and one case of wrist-drop have been observed with intravenous administration of fludarabine phosphate. In Study 1 for oral fludarabine phosphate, there was one report of severe impairment of consciousness that presented concurrent with hemolytic anemia. This patient had enrolled in the study with pre-existing peripheral neurotoxicity. [See Warnings and Precautions (5.1)]
Pulmonary System
Pneumonia, a frequent manifestation of infection in patients with CLL, was observed in two clinical trials conducted with intravenous fludarabine phosphate (16% and 22%) and in two clinical trials with oral fludarabine phosphate (8% and 3%). Pulmonary hypersensitivity reactions to fludarabine phosphate characterized by dyspnea, cough and interstitial pulmonary infiltrate have been observed. In Study 1 conducted with oral fludarabine phosphate, severe pulmonary toxicity was reported in 5 of 78 patients, often in conjunction with respiratory or pulmonary infections and hence not regarded as isolated drug related pulmonary toxicity.
Gastrointestinal System
Gastrointestinal disturbances such as nausea and vomiting, anorexia, diarrhea, stomatitis and gastrointestinal bleeding have been reported in patients treated with fludarabine phosphate. Nausea and vomiting occurred in up to 38% of patients following treatment with oral fludarabine phosphate in the clinical trials.
Cardiovascular
Edema has been frequently reported. One patient developed a pericardial effusion possibly related to treatment with fludarabine phosphate. No other severe cardiovascular events were considered to be drug related.
Genitourinary System
Hemorrhagic cystitis has been reported in patients treated intravenously with fludarabine phosphate.
Skin
Skin toxicity, consisting primarily of skin rashes, has been reported in patients treated with oral and intravenous fludarabine phosphate.
Data in Table 2 are derived from the 159 patients with CLL who received fludarabine phosphate in Study 1 and Study 2.
| ADVERSE REACTIONS | Study 1 (N=78) % |
Study 2 (N=81) % |
| ANY ADVERSE REACTION | 82 | 89 |
| BODY AS A WHOLE | 59 | 77 |
| FEVER | 26 | 11 |
| INFECTION | 12 | 17 |
| PAIN | 5 | 19 |
| FLU SYNDROME | 8 | 5 |
| DIAPHORESIS | 8 | 0 |
| NEUROLOGICAL | 19 | 41 |
| WEAKNESS/FATIGUE (ASTHENIA) | 13 | 31 |
| SWEATING INCREASED | 0 | 14 |
| HEADACHE | 9 | 9 |
| PULMONARY | 37 | 53 |
| COUGH | 21 | 0 |
| COUGH INCREASED | 0 | 6 |
| PNEUMONIA | 8 | 3 |
| DYSPNEA | 1 | 5 |
| SINUSITIS | 1 | 5 |
| UPPER RESPIRATORY INFECTION | 9 | 14 |
| RHINITIS | 3 | 11 |
| BRONCHITIS | 6 | 9 |
| METABOLIC AND NUTRITIONAL | 3 | 31 |
| WEIGHT DECREASED | 1 | 6 |
| LACTIC DEHYDROGENASE INCREASED | 0 | 6 |
| PERIPHERAL EDEMA | 0 | 7 |
| GASTROINTESTINAL | 41 | 28 |
| NAUSEA | 5 | 1 |
| DIARRHEA | 6 | 5 |
| ANOREXIA | 19 | 0 |
| ABDOMINAL PAIN | 8 | 10 |
| CUTANEOUS | 22 | 25 |
| RASH | 5 | 4 |
| SKIN DISORDER | 0 | 6 |
| HERPES SIMPLEX | 8 | 7 |
| GENITOURINARY | 8 | 14 |
| URINARY TRACT INFECTION | 4 | 5 |
| CARDIOVASCULAR | 14 | 17 |
| CHEST PAIN | 0 | 5 |
| MUSCULOSKELETAL | 10 | 19 |
| BACK PAIN | 4 | 9 |
Post Marketing Experience
The following adverse reactions have been identified during post approval use of oral fludarabine phosphate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possibly to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hematopoietic Systems
Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in post-marketing surveillance. 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.
Nervous System
In post-marketing experience, cases of progressive multifocal leukoencephalopathy have been reported. Most cases had a fatal outcome. Many of these cases were confounded by prior and/or concurrent chemotherapy. The median time to onset was approximately one year.
Pulmonary System
In post-marketing experience, cases of severe pulmonary toxicity have been observed with fludarabine phosphate use which resulted in acute respiratory distress syndrome, respiratory distress, pulmonary hemorrhage, pulmonary fibrosis, and respiratory failure. After exclusion of an infectious origin, some patients experienced symptom improvement with corticosteroids.
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