Fludarabine Phosphate Injection

Last updated on RxList: 6/15/2016
Fludarabine Phosphate Injection Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 8/18/2015

Fludarabine Phosphate Injection is a nucleotide metabolic inhibitor indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to, or whose disease has progressed during treatment with, at least one standard alkylating-agent containing regimen. The safety and effectiveness of fludarabine phosphate injection in previously untreated or non-refractory patients with CLL have not been established. Fludarabine phosphate injection is available in generic form. Common side effects of fludarabine phosphate injection include

The recommended adult dose of fludarabine phosphate injection is 25 mg/m² diluted in 100 to 125 cc of 5% dextrose injection USP or 0.9% sodium chloride USP administered intravenously over a period of approximately 30 minutes daily for five consecutive days. Each 5-day course of treatment should commence every 28 days. Fludarabine phosphate injection may interact with pentostatin. Tell your doctor all medications and supplements you use. Fludarabine phosphate injection is not recommended for use during pregnancy; it may harm a fetus. It is unknown if fludarabine phosphate injection passes into breast milk. Breastfeeding while receiving fludarabine phosphate injection is not recommended.

Our Fludarabine Phosphate Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Fludarabine Phosphate Injection Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

In rare cases, fludarabine may cause serious side effects on your nervous system. Seek medical attention right away if you have any numbness or tingling, burning pain, or vision problems.

Call your doctor at once if you have:

  • agitation;
  • sudden chest pain, wheezing, dry cough, feeling short of breath;
  • bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • damage to red blood cells--confusion, weakness, pale or yellowed skin, dark colored urine;
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath; or
  • signs of tumor cell breakdown--tiredness, weakness, muscle cramps, lower back pain, nausea, vomiting, diarrhea, blood in your urine, fast or slow heart rate, tingling in your hands and feet or around your mouth.

Common side effects may include:

  • low blood cell counts;
  • nausea, loss of appetite, vomiting, diarrhea;
  • feeling weak or tired;
  • mouth sores; or
  • swelling in your hands or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Fludarabine Phosphate Injection (Fludarabine Phosphate Injection)

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Fludarabine Phosphate Injection Professional Information

SIDE EFFECTS

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 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 CLL patients treated with fludarabine phosphate. The most frequently reported adverse reactions and those reactions which are more clearly related to the drug are arranged below according to body system.

Hematopoietic Systems

Hematologic events (neutropenia, thrombocytopenia, and/or anemia) were reported in the majority of CLL patients treated with fludarabine phosphate. During 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%. Myelosuppression may be severe, cumulative, and may affect multiple cell lines. Bone marrow fibrosis occurred in one CLL patient treated with fludarabine phosphate.

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.

Life-threatening and sometimes fatal autoimmune hemolytic anemias have been reported to occur in patients receiving fludarabine phosphate. [See WARNINGS AND PRECAUTIONS] The majority of patients rechallenged with fludarabine phosphate developed a recurrence in the hemolytic process.

Metabolic

Tumor lysis syndrome has been reported in CLL patients treated with fludarabine phosphate. 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 CLL patients treated with fludarabine phosphate at the recommended dose. Peripheral neuropathy has been observed in patients treated with fludarabine phosphate and one case of wrist-drop was reported. [See WARNINGS AND PRECAUTIONS]

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

Pneumonia, a frequent manifestation of infection in CLL patients, occurred in 16%, and 22% of those treated with fludarabine phosphate in the MDAH and SWOG studies, respectively. Pulmonary hypersensitivity reactions to fludarabine phosphate characterized by dyspnea, cough and interstitial pulmonary infiltrate have been observed.

In post-marketing experience, cases of severe pulmonary toxicity have been observed with fludarabine phosphate use which resulted in ARDS, respiratory distress, pulmonary hemorrhage, pulmonary fibrosis, and respiratory failure. After an infectious origin has been excluded, some patients experienced symptom improvement with corticosteroids.

Gastrointestinal System

Gastrointestinal disturbances such as nausea and vomiting, anorexia, diarrhea, stomatitis and gastrointestinal bleeding have been reported in patients treated with fludarabine phosphate.

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 with fludarabine phosphate.

Skin

Skin toxicity, consisting primarily of skin rashes, has been reported in patients treated with fludarabine phosphate.

Adverse Reactions From Clinical Trials

Data in Table 1 are derived from the 133 patients with CLL who received fludarabine phosphate in the MDAH and SWOG studies.

TABLE 1: PERCENT OF CLL PATIENTS REPORTING NONHEMATOLOGIC ADVERSE REACTIONS

ADVERSE REACTIONS MDAH
(N=101)
SWOG
(N=32)
ANY ADVERSE REACTION 88 91
BODY AS A WHOLE 72 84
FEVER 60 69
CHILLS 11 19
FATIGUE 10 38
INFECTION 33 44
PAIN 20 22
MALAISE 8 6
DIAPHORESIS 1 13
ALOPECIA 0 3
ANAPHYLAXIS 1 0
HEMORRHAGE 1 0
HYPERGLYCEMIA 1 6
DEHYDRATION 1 0
NEUROLOGICAL 21 69
WEAKNESS 9 65
PARESTHESIA 4 12
HEADACHE 3 0
VISUAL DISTURBANCE 3 15
HEARING LOSS 2 6
SLEEP DISORDER 1 3
DEPRESSION 1 0
CEREBELLAR SYNDROME 1 0
IMPAIRED MENTATION 1 0
PULMONARY 35 69
COUGH 10 44
PNEUMONIA 16 22
DYSPNEA 9 22
SINUSITIS 5 0
PHARYNGITIS 0 9
UPPER RESPIRATORY INFECTION 2 16
ALLERGIC PNEUMONITIS 0 6
EPISTAXIS 1 0
HEMOPTYSIS 1 6
BRONCHITIS 1 0
HYPOXIA 1 0
GASTROINTESTINAL 46 63
NAUSEA/VOMITING 36 31
DIARRHEA 15 13
ANOREXIA 7 34
STOMATITIS 9 0
GI BLEEDING 3 13
ESOPHAGITIS 3 0
MUCOSITIS 2 0
LIVER FAILURE 1 0
ABNORMAL LIVER FUNCTION TEST 1 3
CHOLELITHIASIS 0 3
CONSTIPATION 1 3
DYSPHAGIA 1 0
CUTANEOUS 17 18
RASH 15 15
PRURITUS 1 3
SEBORRHEA 1 0
GENITOURINARY 12 22
DYSURIA 4 3
URINARY INFECTION 2 15
HEMATURIA 2 3
RENAL FAILURE 1 0
ABNORMAL RENAL FUNCTION TEST 1 0
PROTEINURIA 1 0
HESITANCY 0 3
CARDIOVASCULAR 12 38
EDEMA 8 19
ANGINA 0 6
CONGESTIVE HEART FAILURE 0 3
ARRHYTHMIA 0 3
SUPRAVENTRICULAR TACHYCARDIA 0 3
MYOCARDIAL INFARCTION 0 3
DEEP VENOUS THROMBOSIS 1 3
PHLEBITIS 1 3
TRANSIENT ISCHEMIC ATTACK 1 0
ANEURYSM 1 0
CEREBROVASCULAR ACCIDENT 0 3
MUSCULOSKETAL 7 16
MYALGIA 4 16
OSTEOPOROSIS 2 0
ARTHRALGIA 1 0
TUMOR LYSIS SYNDROME 1 0

More than 3000 adult patients received fludarabine phosphate in studies of other leukemias, lymphomas, and other solid tumors. The spectrum of adverse effects reported in these studies was consistent with the data presented above.

Read the entire FDA prescribing information for Fludarabine Phosphate Injection (Fludarabine Phosphate Injection)

© Fludarabine Phosphate Injection Patient Information is supplied by Cerner Multum, Inc. and Fludarabine Phosphate Injection Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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