Fludarabine Phosphate

A to Z Drug Facts

Fludarabine Phosphate

	Actions
	Indications
	Contraindications
	Route/Dosage
	Interactions
	Lab Test Interferences
	Adverse Reactions
	Precautions
Patient Care Considerations
	Administration/Storage
	Assessment/Interventions
	Patient/Family Education

(flew-DAR-uh-BEAN)

Fludara

Powder for injection

50 mg

Class: Purine antimetabolite

Actions Fludarabine is a fluorinated nucleotide analog of the antiviral agent vidarabine. Fludarabine's metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. Fludarabine is rapidly converted to the active metabolite within minutes after IV infusion. The half-life of the metabolite was approximately 10 hr. The mean total plasma clearance was 8.9 L/m² and the mean volume of distribution was 98/L/m². Total body clearance of the metabolite is inversely correlated with serum creatinine, suggesting renal elimination of the compound.

Indications Refractory or progressive chronic B-cell lymphocytic leukemia.

Leukemias, non-Hodgkin's lymphoma.

Contraindications Standard considerations.

Route/Dosage

Chronic Lymphocytic Leukemia

ADULTS: IV 25 to 30 mg/m²/day in single daily doses for 5 consecutive days. Repeat course of therapy q 21 to 28 days for 3 additional courses after maximal response is achieved.

Adjustment in Renal Insufficiency

ADULTS: IV May require dosage reduction. No specific guidelines published.

Interactions

Pentostatin

Concomitant therapy may cause severe or fatal pulmonary toxicity.

Lab Test Interferences None well documented.

Adverse Reactions

CARDIOVASCULAR: Edema. CNS: Malaise, fatigue, weakness (common); delayed, potentially fatal, neurotoxicity consisting of seizures, blindness, and coma associated with high dose fludarabine; incontinence, paresthesias. DERMATOLOGIC: Maculopapular rash; seborrhea; pruritus. GI: Anorexia; diarrhea; mucositis; GI bleeding; altered taste sensation. HEMATOLOGIC: Bone marrow suppression, neutrophil nadir at 13 days, platelet nadir at 16 days. METABOLIC: Fever; chills; hyperglycemia; tumor lysis syndrome manifested as hyperphosphatemia; hyperkalemia, hyperuricemia, hypocalcemia, metabolic acidosis, and flank pain. MUSCULOSKELETAL: Myalgia. RENAL: Renal dysfunction and hematuria related to tumor lysis syndrome. RESPIRATORY: Cough; dyspnea; diffuse interstitial pneumonitis. SPECIALSENSES: Visual disturbances; hearing loss; auditory hallucinations.

Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy not established. Dose-dependent toxicity: There are clear dose-dependent toxic effects seen with fludarabine. Bone marrow suppression: Severe bone marrow suppression, notably anemia, thrombocytopenia, and neutropenia, occurred. Renal function: Administer cautiously. Tumor lysis syndrome: Tumor lysis syndrome has occurred.

PATIENT CARE CONSIDERATIONS

Administration/Storage

Refrigerate powder for injection. Solutions contain no preservatives; use within 24 hr of reconstitution. The manufacturer recommends use within 8 hr of reconstitution.
Reconstitute by adding 2 mL of Sterile Water for Injection to a 50 mg vial; yields a 25 mg/mL solution. Agitate the vial to dissolve the drug.
Prior to administration, dilute with 100 to 125 mL of 5% Dextrose or 0.9% Sodium Chloride.
Administer by IV infusion over 30 min, IV bolus over 15 min, or continuous IV infusion over 2 days.
Follow procedures for proper handling and disposal of anticancer drugs. Wear gloves and avoid skin exposure and inhalation of fumes.

Assessment/Interventions

Closely monitor patients with a Ccr less than 50 mL/min for increased toxicity, such as bone marrow suppression.
Monitor CBC, differential, and platelet counts at baseline and periodically throughout each course of fludarabine.
Monitor neurologic status because neurotoxicity can occur even with low doses.
Monitor electrolytes at baseline and throughout each course, especially during the first week of therapy when tumor lysis is more likely to occur.
Monitor urine for red blood cells, often the first sign of tumor lysis syndrome.
Hyperuricemia may occur because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.

OVERDOSAGE: SIGNS & SYMPTOMS
	Irreversible CNS toxicity characterized by delayed blindness, coma and death; severe thrombocytopenia and neutropenia

Patient/Family Education

Explain name, action, and potential side effects of drug.
Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
Advise patient, family, or caregiver that medication may be used in combination with other agents to achieve maximum benefit possible.
Review dosing schedule with patient, family, or caregiver.
Advise patient, family, or caregiver to immediately report any of the following symptoms to health care provider: rash; fever, chills or other signs of infection; sores in mouth; unusual bleeding or bruising; dark urine; yellowing of skin or eyes.
Advise patient, family, or caregiver to report any of the following symptoms to health care provider: persistent nausea, vomiting or appetite loss; persistent or worsening general body weakness.
Instruct patient to not take any prescription or otc medications or dietary supplements unless advised by health care provider.
Caution women of childbearing potential to avoid becoming pregnant while being treated.
Instruct women of childbearing potential to notify health care provider if they become pregnant, plan on becoming pregnant, or are breastfeeding.
Advise patient that frequent follow-up visits and laboratory tests will be required to monitor therapy and to be sure to keep appointments.