Names and pronunciation
(floo-dar′a-been)
PDF page 570
Loading InternPractice…
Drug reference
(floo-dar′a-been)
PDF page 570
Func. class.: Antineoplastic, antime- tabolite
PDF page 570
Chem. class.: Purine antagonist
PDF page 570
ACTION: Inhibits DNA synthesis by inhibition of DNA polymerase and ribo- nucleotide reductase; also inhibits DNA primase and DNA ligase
PDF page 571
USES: Chronic lymphocytic leukemia
PDF page 571
CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity
PDF page 571
Black Box Warning: Hemolytic anemia, bone marrow suppression, coma, sei- zures, visual disturbances Black Box Warning: Increase: pulmo- nary toxicity—pentostatin, do not use together NURSING CONSIDERATIONS Black Box Warning: Severe bone mar- row suppression (anemia, thrombocyto- penia, and neutropenia): may be cumu- lative. Time to nadir 13 days (range: 3-25 days) for granulocytes and 16 days (range: 2-32 days) for platelets. Monitor those with bone marrow impairment closely for excess toxicity; may require dosage reductions • Autoimmune effects: Instances of life- threatening and sometimes fatal autoim- mune phenomena, such as hemolytic ane- mia, autoimmune thrombocytopenia/ thrombocytopenic purpura, Evans syn- drome, and acquired hemophilia, have been reported to occur after 1 or more cy- cles of treatment with fludarabine. Patients undergoing treatment should be evaluated and closely monitored for hemolysis Black Box Warning: Autoimmune effects: May be life-threatening, hemo- lytic anemia, autoimmune thrombocyto- penia/thrombocytopenic purpura, Evans syndrome, and acquired hemophilia, have been reported after 1 or more cycles, evaluate and closely monitored for he- molysis, corticosteroids may be needed • Tumor lysis syndrome: Risk is in- creased in patients with large tumor burden prior to treatment. Hydration and prophylac- tic antihyperuricemic therapy may be used Black Box Warning: Neurotoxicity: Higher-than-recommended doses (up to 96 mg/m2/day for 5-7 days) may cause severe neurologic toxicity (delayed blind- ness, coma, death); similar neurotoxicity (agitation, coma, confusion, seizure) has been reported (rare) with standard CLL doses (25 mg/m2/day for 5 days). Symp- toms of neurotoxicity due to high doses appeared from 21-60 days following the last dose, neurotoxicity may occur as early as 7 days and up to 225 days Black Box Warning: Combination with pentostatin: Do not use together, fatal pulmonary toxicity may occur Black Box Warning: Experienced phy- sician: Injection should be administered under the supervision of a qualified health care provider experienced in the use of antineoplastic therapy • PML: PML (usually fatal) due to JC vi- rus has been reported; most cases were in patients who had received prior and/or other concurrent chemotherapy. Onset may be a few weeks or may be delayed up to 1 yr. Evaluate any neurological change promptly • Transfusion-associated graft-ver- sus-host disease: Patient should only receive irradiated blood products due to the potential for transfusion-related GVHD • Pregnancy/breastfeeding: Not to be used in pregnancy or breastfeeding; ef- fective contraception should be used by females and males during and for ≥6 mo after last dose • Monitor CBC with differential, platelet count, AST, ALT, serum creatinine, serum albumin, uric acid; monitor for signs of infection, neurotoxicity, and tumor lysis syndrome
PDF pages 571, 572
SIDE EFFECTS CV: Edema, angina pectoris, cardiac arrhythmia, cardiac failure, CVA, MI, supra- ventricular tachycardia, DVT, phlebitis CNS: Fatigue, cortical blindness, coma, paralysis, chills, paresthesia, malaise, headache, sleep disorder INTEG: Rash, diaphoresis, alopecia, pruritus GI: Nausea, vomiting, anorexia, diarrhea, GI hemorrhage, stomatitis, cholelithiasis, esophagitis, constipation, mucositis GU: UTI, hematuria, dysuria HEMA: Anemia, neutropenia, thrombocy- topenia, bone marrow depression EENT: Visual disturbance, hearing loss RESP: Cough, pneumonia, dyspnea, URI, pharyngitis, hypersensitivity, pneumoni- tis, hemoptysis, sinusitis MISC: Fever, infection, myalgia, hyper- sensitivity, hyperglycemia, TLS
PDF pages 571, 572
INTERACTIONS Increase: toxicity—other myelosupres- sives Increase: adverse reactions—live virus vaccines, bring up to date before treatment
PDF page 572
DOSAGE AND ROUTES Chronic lymphocytic leukemia (CLL), refractory or progressive • Adult: IV 25 mg/m2 once daily for 5 consecutive days q28days; continue for at least 3 additional cycles after maximal response is achieved; PO (Canada only) 40 mg/m2 once daily for 5 consecutive days q28days Acute myeloid leukemia, newly diagnosed (Unlabeled) • Adult: IV 30 mg/m2/day for 5 days (cytarabine ± G-CSF ± idarubicin (FA, FLAG, or FLAG-IDA regimens), followed by consolidation therapy Acute myeloid leukemia, refractory or high/poor-risk patients (unlabeled) • Adult: IV 30 mg/m2/day × 5 days (with cytarabine and filgrastim [FLAG regimen]), may repeat once for partial remission or 30 mg/m2/day for 5 days for 1 or 2 cycles (in combination with cytarabine, idarubicin, and filgrastim [FLAG-IDA regimen]) Hematopoietic stem cell transplant (allogeneic) myeloablative condi- tioning regimen (off-label use) • Adult: IV 40 mg/m2/day for 4 days (with busulfan) beginning 6 days prior to transplantation Hematopoietic stem cell transplant (allogeneic) reduced-intensity con- ditioning regimen (unlabeled) •Adult: IV 30 mg/m2/day × 5 days (with melphalan and alemtuzumab) prior to transplant or 30 mg/m2/day for 6 days beginning 10 days prior to transplant or 30 mg/m2/day for 5 days beginning 6 days prior to transplant (with busulfan with or without antithymocyte globulin) Hematopoietic stem cell transplant (allogeneic) nonmyeloablative con- ditioning regimen (unlabeled) • Adult: IV 30 mg/m2/day × 3 doses be- ginning 5 days prior to transplant (with cy- clophosphamide and rituximab) or 30 mg/ m2/day for 3 doses beginning 4 days prior to transplant (with total body irradiation) F
PDF page 571
Available forms: Solution for injection 50 mg /2 mL (2 mL); powder for injec- tion 50 mg/2 mL Administer IV route • Reconstitute lyophilized powder with 2 mL SWFI to a concentration of 25 mg/mL • Dilute in 100 to 125 mL D5W or NS, give over 30 min (CLL) • Store vials under refrigeration or at room temperature, as specified accord- ing to each manufacturer’s labeling. Pro- tect from light. Reconstituted solution or vials of the solution for injection that have been punctured (in use) should be used within 8 hr PO route • Tablet [Canadian product] give with or without food; swallow whole with wa- ter; do not chew, break, or crush • Tablet [Canadian product]: Store at 15°C to 30°C (59°F to 86°F); keep in packaging until use
PDF page 571
Assess:
PDF page 572
Evaluate: • Therapeutic response: Inhibiting CLL
PDF page 572
Patient and caregiver information: • To report mouth irritation, mouth sores, muscle pain • PML: To report confusion, depres- sion, trouble with memory, behavioral changes, change in strength on one side is greater than the other, trouble speaking, change in balance, or vision changes • Bleeding: To report vomiting blood or vomit that looks like coffee grounds or is black; coughing up blood; blood in the urine; black, red, or tarry stools; bleed- ing from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persis- tent bleeding • Tumor lysis syndrome: To report fast heartbeat or abnormal heartbeat; fainting; unable to pass urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling fatigued • To report shortness of breath or other trouble breathing, cough that is new or worse • Stevens-Johnson syndrome/toxic epidermal necrolysis: To report red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes • Signs of an allergic reaction: To re- port rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swell- ing of the mouth, face, lips, tongue, throat • Pregnancy/breastfeeding: To report if pregnancy is planned or suspected or if breastfeeding; to use contraceptives (males and females taking product) during and for ≥6 mo after last dose
PDF page 573
PHARMACOKINETICS Onset, peak, duration unknown, half-life 20 hr
PDF page 572
• Adult: IV 25 mg/m2 once daily for 5 consecutive days q28days; continue for at least 3 additional cycles after maximal response is achieved; PO (Canada only) 40 mg/m2 once daily for 5 consecutive days q28days Acute myeloid leukemia, newly diagnosed (Unlabeled)
PDF page 571
• Adult: IV 30 mg/m2/day for 5 days (cytarabine ± G-CSF ± idarubicin (FA, FLAG, or FLAG-IDA regimens), followed by consolidation therapy Acute myeloid leukemia, refractory or high/poor-risk patients (unlabeled)
PDF page 571
• Adult: IV 30 mg/m2/day × 5 days (with cytarabine and filgrastim [FLAG regimen]), may repeat once for partial remission or 30 mg/m2/day for 5 days for 1 or 2 cycles (in combination with cytarabine, idarubicin, and filgrastim [FLAG-IDA regimen]) Hematopoietic stem cell transplant (allogeneic) myeloablative condi- tioning regimen (off-label use)
PDF page 571
• Adult: IV 40 mg/m2/day for 4 days (with busulfan) beginning 6 days prior to transplantation Hematopoietic stem cell transplant (allogeneic) reduced-intensity con- ditioning regimen (unlabeled)
PDF page 571
•Adult: IV 30 mg/m2/day × 5 days (with melphalan and alemtuzumab) prior to transplant or 30 mg/m2/day for 6 days beginning 10 days prior to transplant or 30 mg/m2/day for 5 days beginning 6 days prior to transplant (with busulfan with or without antithymocyte globulin) Hematopoietic stem cell transplant (allogeneic) nonmyeloablative con- ditioning regimen (unlabeled)
PDF page 571
• Adult: IV 30 mg/m2/day × 3 doses be- ginning 5 days prior to transplant (with cy- clophosphamide and rituximab) or 30 mg/ m2/day for 3 doses beginning 4 days prior to transplant (with total body irradiation) F
PDF page 571