Dosing and uses of Fludara, Oforta (fludarabine)
Adult dosage forms and strengths
injectable solution
- 25mg/mL
powder for injection
- 50mg
tablet
- 10mg
B-Cell Chronic Lymphocytic Leukemia
25 mg/sq.meter IV infusion over 30 minutes qD x5 days (up to 30 mg/sq.meter)
40 mg/sq.meter PO x5 days
Repeat q28Days
Renal impairment
- CrCl 30-70 mL/min: reduce by 20%
- CrCl <30 mL/min: IV not recommended; PO reduce 50%
Non-Hodgkin Lymphoma (Orphan)
Treatment and management of non-Hodgkin lymphoma
Orphan indication sponsor
- Berlex Laboratories, Inc; 15049 San Pablo Avenue, P.O. Box 4099; Richmond, CA 94804-0099
Other Information
Monitor: CBC, chemistries, pulmonary function
Other Indications & Uses
Off-label: hairy cell leukemia, NHL, prolymphocytic leukemia, mycosis fungoides, Hodgkin's disease
Pediatric dosage forms and strengths
Safety and efficacy not established
Fludara, Oforta (fludarabine) adverse (side) effects
>10%
Fever (69%)
Objective weakness (65%)
Anemia (60%)
Neutropenia (60%)
Thrombocytopenia (55%)
Leukopenia (partly therapeutic)
Infection (44%-not necessarily drug-induced)
Cough (44%)
Pain (44%)
Fatigue (38%)
N/V (36%)
Anorexia (34%)
Malaise (22%)
Dyspnea (22%)
Pneumonia (9-22%)
Edema (19%)
Myalgia (16%)
URI (16%)
UTI (15%)
Rash (15%)
Diarrhea (15%)
Visual disturbances (15%)
Diaphoresis (13%)
GI bleeding (13%)
Paresthesia (12%)
1-10% (selected)
Abdominal pain (10%)
Back pain (9%)
Headache (9%)
Pharyngitis (9%)
Stomatitis (9%)
Flu like syndrome (5-9%)
Malaise (6%)
Angina (6%)
Hearing Loss (2-6%)
Peripheral edema (7%)
Alopecia (3%)
Constipation (1-3%)
Arrhythmia (3%)
DVT (1%)
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Bone marrow suppression may occur. Fludarabine has been associated with severe neurologic effects, including blindness, coma when high doses were used in patients with acute leukemia. Agitation, coma, confusion, and seizures have been reported in patients treated at recommended doses for the treatment of chronic lymphocytic leukemia
If one or more cycles of treatment with fludarabine administered, autoimmune phenomena including acquired hemophilia, autoimmune thrombocytopenia/thrombocytopenic purpura, Evan syndrome, and hemolytic anemia may occur. Monitor patients closely for hemolysis
Fludarabine in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia is not recommended due to a high incidence of fatal pulmonary toxicity
Contraindications
Hypersensitivity
Concomitant pentostatin: risk of fatal pulmonary toxicity
IV: severe renal impairment
Cautions
Bone marrow depression, renal impairment, elderly
Allopurinol and hydration recommended for patients newly diagnosed with CLL or those at risk of tumor lysis syndrome
Very high doses (and rarely, normal doses) have caused irreversible or fatal neurotoxicity manifesting after 21-60 days
Risk of potentially fatal autoimmune hemolytic anemia
Avoid pregnancy
No efficacy in children
Pregnancy and lactation
Pregnancy category: d
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Fludara, Oforta (fludarabine)
Peak plasma time: 2 hr
Vd: 96-98 L/sq.meter
Protein bound: 19-29%
Metabolites: 2-fluoro-ara-ATp
Clearance: 8.9 L/hr/sq.meter
Excretion: urine
Mechanism of action
Fluorinated purine analog, inhibits DNA polymerase alpha
Administration
IV Incompatibilities
Y-site: acyclovir, amphotericin B, chlorpromazine, daunorubicin, ganciclovir, hydroxyzine, prochlorperazine
IV Compatibilities
Y-site (partial list): allopurinol, ampicillin, bleomycin, carboplatin, most cephalosporins, cisplatin, dactinomycin, doxorubicin, fluconazole, hydromorphone, imipenem-cilastatin, lorazepam, MgSO4, metoclopramide, morphine SO4, KCl, NaHCO3, TMP-SMX, vancomycin, zidovudine
IV Preparation
Reconstitute powder for inj with 2 mL SWI to result in a concentration of 25 mg/mL
Standard IV dilution: dose/100 mL D5W or Ns
IV Administration
IV infusion over 30 min recommended by Mfr; has been given as continuous infusion or by rapid injection but risk of toxicity may be higher
Storage
Store intact vials under refrigeration
