Fludara


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Fludara

 [floo-dar´ah]
trademark for a preparation of fludarabine phosphate, an antineoplastic agent.

fludarabine

(floo-dar-a-been) ,

Fludara

(trade name),

Oforta

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimetabolites
Pregnancy Category: D

Indications

B-cell chronic lymphocytic leukemia unresponsive to standard therapy.Non-Hodgkin's lymphoma.

Action

Converted intracellularly to an active phosphorylated metabolite that inhibits DNA synthesis.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: Bioavailability of active metabolite, 2–fluoro-ara-A, is 50–65%.
Distribution: Extensively distributed.
Metabolism and 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)

ROUTEONSETPEAKDURATION
POunknown13–16 daysunknown
IV7 wk†13–16 daysunknown
†Median time to response

Contraindications/Precautions

Contraindicated in: Hypersensitivity to fludarabine, mannitol, or sodium hydroxide;Patients taking pentostatin; Obstetric / Lactation: Pregnancy or lactation;Severe renal impairment (CCr <30 mL/min) (for intravenous).
Use Cautiously in: Moderate renal impairment (↓ dose if CCr <70 mL/min); Obstetric: Patients with childbearing potential;Bone marrow depression; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • neurotoxicity (life-threatening)
  • fatigue (most frequent)
  • agitation
  • coma
  • confusion
  • headache
  • malaise
  • weakness

Ear, Eye, Nose, Throat

  • hearing loss
  • visual disturbances

Respiratory

  • pulmonary hypersensitivity (life-threatening)
  • cough (most frequent)
  • pneumonia (most frequent)
  • dyspnea
  • sinusitis

Cardiovascular

  • edema

Gastrointestinal

  • gi bleeding (life-threatening)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • anorexia
  • esophagitis
  • mucositis
  • stomatitis
  • vomiting (most frequent)

Genitourinary

  • dysuria
  • hematuria
  • urinary tract infection

Dermatologic

  • rashes (most frequent)

Endocrinologic

  • gonadal suppression

Hematologic

  • pancytopenia (life-threatening)
  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)
  • hemolytic anemia

Musculoskeletal

  • myalgia

Neurologic

  • peripheral neuropathy

Miscellaneous

  • fever
  • tumor lysis syndrome

Interactions

Drug-Drug interaction

↑ 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

Oral (Adults) 40 mg/m2 daily for 5 days; repeat course every 28 days.
Intravenous (Adults) 25 mg/m2 daily for 5 days; repeat course every 28 days.

Renal Impairment

Oral Intravenous (Adults) CCr 30–70 mL/min—↓ dose by 20%.

Renal Impairment

Oral (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

Nursing implications

Nursing 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.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Risk for injury (Side Effects)

Implementation

  • high alert: 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.
  • Oral: 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.
  • Intravenous Administration
  • pH: 7.2–8.2.
  • Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers (see ). 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.
  • Intravenous: 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.
  • Y-Site Compatibility: alfentanil, allopurinol, amifostine, amikacin, aminophylline, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbactam, amsacrine, anidulafungin, argatroban, atracurium, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium acetate, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doxacurium, doxorubicin hydrochloride, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, floxuridine, fluconazole, fluorouracil, foscarnet, fosphenytoin, furosemide, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hetastarch, hydralazine, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, insulin, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, mesna, metaraminol, methohexital, methotrexate, methyldopate, methylprednisolone sodium succinate, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, multivitamins, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, pamidronate, pancuronium, pemetrexed, pentamidine, pentazocine, pentobarbital, pentostatin, phenobarbital, phentolamine, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, promethazine, propranolol, ranitidine, remifentanil, rituximab, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, voriconazole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: acyclovir, amiodarone, amphotericin B colloidal, chlorpromazine, dantrolene, daunorubicin hydrochloride, diazepam, ganciclovir, hydroxyzine, idarubicin, pantoprazole, phenytoin, prochlorperazine, quinapristin/dalfopristin, trastuzumab

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.

Evaluation/Desired Outcomes

  • Improvement of hematopoietic values in leukemias.

Fludara

a trademark for an antineoplastic (fludarabine).

Fludara

A brand name for FLUDARABINE.
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References in periodicals archive ?
Fludarabine (Genzyme's Fludara, Bayer HealthCare's Fludara/Beneflur, generics) + cyclophosphamide (Bristol-Myers Squibb's Cytoxan, Pfizer's Cyclophospham, generics) + rituximab (Roche/Genentech/Chugai Seiyaku/Zenyaku Kogyo's Rituxan/MabThera)
and ILEX Oncology, serving as CEO in both, where he led teams that were responsible for the clinical development of numerous important therapeutic products, four of which are currently used in the practice of medicine: Betaseron, Fludara, CAMPATH, and Clolar.
MabCampath is the first and only humanized monoclonal antibody approved for B-CLL therapy and the first product with proven efficacy in CLL patients who have failed both alkylating agents and Fludara (fludarabine phosphate) treatment.
Eli Lilly Fludara Fujifilm Fujisawa Pharmaceutical Company Ltd Genentech Genmab Gilead Sciences GlaxoSmithKline Glenmark Pharmaceuticals Ltd ImClone LLC Janssen Pharmaceuticals, Inc.
MabCampath, also marketed as Campath(R) in the United States, is the first and only humanized monoclonal antibody approved for CLL and the first drug with proven efficacy in CLL patients who have failed both alkylating agents and Fludara (fludarabine phosphate) treatment.
Plus, there are four drugs in the market; such as Fludara (Fludarabine), Campath, Treanda, and Arzerra.
According to a study published in the October issue of the Journal of Clinical Oncology, combination therapy with MabCampath (alemtuzumab) and Fludara (fludarabine phosphate) (FluCam) is effective in patients with B-CLL who had failed prior intervention, with an overall response rate (ORR) of 83 percent.
Fludarabine phosphate for injection, USP (generic equivalent to Fludara , distributed by Bayer HealthCare Pharmaceuticals) is 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.
Rationales for this regimen were proven efficacy of cyclophospate (CP) and doxorubicin (Dox) in T-cell lymphomas, high efficacy of Fludara and CP (FC) in other lymphomas and the possible synergism of antibodies with cytotoxic drugs.
Benefits Also Seen in Patients Refractory to MabCampath or Fludara Monotherapy
Genzyme Corporation (Nasdaq: GENZ) announced data from its CAM314 randomized Phase 3 clinical trial comparing Campath([R] )(alemtuzumab) in combination with Fludara([R]) (fludarabine phosphate) (FluCAM) to Fludara alone in patients with relapsed and refractory chronic lymphocytic leukemia (CLL) demonstrated that the FluCAM regimen significantly reduced the risk of disease progression or death compared to single-agent Fludara.