fludarabine

Absorption: Bioavailability of active metabolite, 2–fluoro-ara-A, is 50–65%.

Distribution: Extensively distributed.

Metabolism/Excretion: Following administration, rapidly converted to an active metabolite (2–fluoro-ara-A), which, when phosphorylated intracellularly, exerts antineoplastic activity; 40% of initial active metabolite excreted unchanged by the kidneys.

Half-Life: 20 hr (for initial active metabolite).

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	13–16 days	unknown
IV	7 wk‡	13–16 days	unknown

‡Median time to response.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to fludarabine, mannitol, or sodium hydroxide;
Patients taking pentostatin;
OB: Pregnancy or lactation;
Severe renal impairment (CCr <30 mL/min) (for intravenous).

Use Cautiously in:

Moderate renal impairment (↓ dose if CCr <70 mL/min);
OB: Patients with childbearing potential;
Bone marrow depression;
Pedi: Safety not established.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema

Derm: rashes

EENT: hearing loss, visual disturbances

Endo: gonadal suppression

GI: diarrhea, nausea, vomiting, anorexia, esophagitis, GI BLEEDING, mucositis, stomatitis

GU: dysuria, hematuria, urinary tract infection

Hemat: anemia, leukopenia, thrombocytopenia, hemolytic anemia, PANCYTOPENIA

MS: myalgia

Neuro: fatigue, agitation, coma, confusion, headache, malaise, NEUROTOXICITY, peripheral neuropathy, weakness

Resp: cough, pneumonia, dyspnea, PULMONARY HYPERSENSITIVITY, sinusitis

Misc: fever, tumor lysis syndrome

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow suppression with other antineoplastics or radiation therapy.
Concomitant use with pentostatin↑ risk of potentially fatal pulmonary toxicity (concurrent use not recommended).

Route/Dosage ⬆ ⬇

PO (Adults ): 40 mg/m² daily for 5 days; repeat course every 28 days.
IV (Adults ): 25 mg/m² daily for 5 days; repeat course every 28 days.

Renal Impairment

PO IV (Adults ): CCr 30–70 mL/min: ↓dose by 20%.

Renal Impairment

PO (Adults ): CCr <30 mL/min: ↓dose by 50%.

Availability ⬆ ⬇

(Generic available)

Tablets: 10 mg
Powder for injection: 50 mg/vial
Solution for injection: 25 mg/mL

Assessment ⬆ ⬇

Assess patient for visual changes, weakness, confusion, and changes in level of consciousness during and for 60 days following therapy, as neurologic effects resulting in blindness, coma, and death have been reported. Therapy may be delayed or discontinued if neurotoxicity occurs.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Monitor respiratory status, intake and output ratios, and daily weights. Report significant changes or symptoms of pulmonary hypersensitivity (cough, fever, shortness of breath).
Assess nutritional status. Administering an antiemetic prior to and periodically during therapy and adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
May cause tumor lysis syndrome, resulting in hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, hyperkalemia, hematuria, urate crystalluria, and renal failure. Monitor for flank pain and hematuria. Uric acid nephropathy may be prevented by adequate oral hydration. Allopurinol and alkalization of the urine may also be used to treat elevated uric acid concentrations.

Lab Test Considerations:

Monitor CBC with differential prior to and frequently during therapy. The nadir for leukopenia occurs in 13 days (range 3–25 days) and for thrombocytopenia in 16 days (range 2–32 days) after administration.
- Monitor serum uric acid concentrations periodically during therapy; may be ↑ as part of tumor lysis in patients with large tumor burdens.
- May cause ↑ AST and serum alkaline phosphatase concentrations.

Implementation ⬆ ⬇

Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations, and infusion pump settings.
PO and IV doses are different.
PO: Administer daily without regard to food for 5 days every 28 days. Swallow tablets whole; do not break, crush, or chew. Avoid handling tablets directly.

IV Administration:

Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers. Unopened vials should be refrigerated. The 5-day course of therapy is continued every 28 days until patient is in complete remission or until neurotoxicity develops.
IV: Reconstitute with 2 mL of sterile water for injection; solid cake should dissolve in <15 sec. Concentration: 25 mg/mL. Reconstituted solution is stable for 8 hr.
Intermittent Infusion: Diluent: Dilute further in 100–125 mL of 0.9% NaCl or D5W.
Rate: Infuse over 30 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take fludarabine as directed. Avoid handling tablets; wash hands with soap and water if touching tablet or powder from tablets. Notify health care professional if a dose is missed.
Caution patient to avoid crowds and persons with known infections. Health care professional should be informed immediately if symptoms of infection (chills, cough, or burning pain on urination) occur.
Instruct patient to report unusual bleeding. Advise patient of thrombocytopenia precautions (use soft toothbrush and electric razor; avoid contact sports and other situations in which injury might occur). Do not drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Consult health care professional if pain interferes with eating. Stomatitis pain treatment may require opioid analgesics.
Advise patient that this medication may have teratogenic effects. Contraception should be used during therapy and for at least 6 mo after therapy is concluded.
Emphasize the need for periodic lab tests to monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇