FLUDARABINE
| FLUDARABINE (flu-dar'a-bine) Fludara Classifications: antineoplastic; antimetabolite, purine antagonist; immunosuppressant; Therapeutic:antineoplastic; antimetabolite; immunosuppressant Prototype: Mercaptopurine Pregnancy Category: D |
Availability
50 mg powder for injection; 25 mg/mL solution for injection
Action
Believed to act by inhibiting DNA polymerase alpha, ribonucleotide reductase, and DNA primase, thus inhibiting DNA synthesis in tumor-sensitive cells.
Therapeutic Effect
Fludarabine has cytotoxic effects on lymphocytic leukemia and lymphoma as well as immunosuppressant properties.
Uses
Treatment of B-cell chronic lymphocytic leukemia (CLL) in patients who fail to respond to a regimen containing at least one standard alkylating agent.
Unlabeled Uses
Non-Hodgkin's lymphoma; in combination therapy for the treatment of primary resistant or relapsing acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and secondary AML; cutaneous T-cell lymphoma; macroglobulinemia; myelodysplastic syndrome; prolymphocytic leukemia (PLL); stem-cell transplant preparation.
Contraindications
Hypersensitivity to fludarabine; concomitant administration of pentostatin; pregnancy (category D); lactation. Safety and efficacy in children have not been established.
Cautious Use
Renal impairment; patients at risk for tumor lysis syndrome; history of herpes or viral infection.
Route & Dosage
| Treatment of Unresponsive B-cell Chronic Lymphocytic Leukemia Adult: IV 25 mg/m2 q.d. x 5 d; repeat q28d Renal Impairment Clcr 30–70 mL/min/1.73 m2: 20% dose reduction; <30 mL/min/1.73 m2: should not receive fludarabine |
Administration
| Intravenous PREPARE: IV Infusion: Exercise caution in the preparation and handling of fludarabine. Avoid exposure by inhalation or direct contact with skin or mucous membranes. Reconstitute each 50 mg vial by adding 2 mL of sterile water for injection to yield 25 mg/mL. The solution should dissolve within 15 s and have a pH of 7.2-8.2. Further dilute in 100–125 mL of D5W or NS. Administer within 8 h of reconstitution. ADMINISTER: IV Infusion: Give over 30 min. INCOMPATIBILITIES Y-site: Acyclovir, amphotericin B, chlorpromazine, daunorubicin, ganciclovir, hydroxyzine, prochlorperazine. |
- Store unreconstituted vials at 2°–8° C (36°–46° F). Discard any unused reconstituted product.
Adverse Effects (≥1%)
Body as a Whole: Fever, chills, fatigue, infection, pain, malaise, diaphoresis, anaphylaxis, hyperglycemia, dehydration. CNS: Weakness, paresthesia. CV: Edema. GI: Nausea, vomiting, diarrhea, anorexia, stomatitis, GI bleeding, esophagitis, mucositis. Hematologic: Neutropenia, thrombocytopenia, hemolytic anemia. Musculoskeletal: Myalgia. Respiratory: Cough, pneumonia, dyspnea, sinusitis, pharyngitis, upper respiratory tract infection. Skin: Rash, pruritus. Special Senses: Visual disturbance, hearing loss. Urogenital: Dysuria, urinary infection, hematuria.Interactions
Drug: Use with pentostatin increases risk of severe pulmonary toxicity. Do not give live vaccines due to decreased immune response.Pharmacokinetics
Metabolism: Rapid conversion to active metabolite (2-fluoro-ara-A). Elimination: Renal. Half-Life: 7–12 h.Nursing Implications
Assessment & Drug Effects
- Review creatinine clearance values prior to drug administration. A 20% dose reduction is recommended for Clcr 30–70 mL/min. Withhold drug and notify physician if Clcr <30 mL/min.
- Monitor for and report S&S of hemolysis, infection, tumor lysis syndrome (e.g., flank pain, hematuria), peripheral neuropathy, or respiratory distress.
- Lab tests: Baseline CBC with differential and platelet count, repeat prior to each treatment cycle, and more often as indicated; periodic serum electrolytes, serum uric acid, and renal function tests.
Patient & Family Education
- Report any of the following to a health care provider: fever, chills, cough, sore throat, or other signs of infection; pain or difficulty passing urine; signs of bleeding such as easy bruising, black, tarry stools, nosebleeds; signs of anemia such as excessive weakness, lightheadedness, or confusion; difficulty breathing or shortness of breath; decreased vision; mouth sores or skin rash.
- Avoid activities that could cause physical injury and predispose to severe bleeding.
- Women of childbearing age should avoid becoming pregnant while receiving fludarabine.
Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; 
Canadian drug name; 
Prototype drug