fludarabine

Purine Analogs

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Oral tablets/capsules: Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Injectables: Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Wash the affected area thoroughly with soap and water if the fludarabine solution comes into contact with the skin or mucous membranes; rinse eyes thoroughly with plain water.
Emetic Risk
IV Doses: Minimal
Oral Doses: Minimal/Low
Administer prn antiemetics as necessary.
Extravasation Risk
Nonvesicant

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Fludarabine phosphate injection is available as a preservative-free 50-mg lyophilized powder vial or as a 25-mg/mL preservative-free solution vial; discard any remaining contents in the vial after 8 hours from reconstitution or initial entry.[64041] [64042]
Reconstitution:
Add 2 mL of Sterile Water for injection to the 50-mg lyophilized powder vial for a final concentration of 25 mg/mL.
The solid cake powder should completely dissolve in 15 seconds or less.[64042]
Dilution:
Dilute the calculated dose of fludarabine in 100 mL or 125 mL of 5% Dextrose injection or 0.9% Sodium Chloride injection.
Do not mix with other drugs.
Intravenous (IV) infusion
Administer the diluted admixture IV over approximately 30 minutes.[64041] [64042]

visual impairment / Early / 3.0-15.0
GI bleeding / Delayed / 3.0-13.0
hearing loss / Delayed / 2.0-6.0
thrombosis / Delayed / 1.0-3.0
stroke / Early / 0-3.0
myocardial infarction / Delayed / 0-3.0
heart failure / Delayed / 0-3.0
hepatic failure / Delayed / 0-1.0
acute cerebellar syndrome / Early / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
proteinuria / Delayed / 0-1.0
tumor lysis syndrome (TLS) / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
pancytopenia / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
leukoencephalopathy / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
pericardial effusion / Delayed / Incidence not known
intracranial bleeding / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
seizures / Delayed / Incidence not known
coma / Early / Incidence not known
hemorrhagic cystitis / Delayed / Incidence not known
hyperkalemia / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
pemphigus / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known

anemia / Delayed / 60.0-60.0
neutropenia / Delayed / 59.0-59.0
thrombocytopenia / Delayed / 55.0-55.0
dyspnea / Early / 16.0-22.0
edema / Delayed / 8.0-19.0
stomatitis / Delayed / 0-9.0
pneumonitis / Delayed / 0-6.0
hemoptysis / Delayed / 1.0-6.0
angina / Early / 0-6.0
hyperglycemia / Delayed / 1.0-6.0
dysuria / Early / 3.0-4.0
elevated hepatic enzymes / Delayed / 1.0-3.0
esophagitis / Delayed / 0-3.0
cholelithiasis / Delayed / 0-3.0
constipation / Delayed / 1.0-3.0
phlebitis / Rapid / 1.0-3.0
supraventricular tachycardia (SVT) / Early / 0-3.0
hematuria / Delayed / 2.0-3.0
osteoporosis / Delayed / 0-2.0
hypoxia / Early / 0-1.0
dysphagia / Delayed / 0-1.0
depression / Delayed / 0-1.0
bleeding / Early / 0-1.0
dehydration / Delayed / 0-1.0
bone marrow suppression / Delayed / Incidence not known
hemolysis / Early / Incidence not known
respiratory depression / Rapid / Incidence not known
hyperamylasemia / Delayed / Incidence not known
neurotoxicity / Early / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
confusion / Early / Incidence not known
hypocalcemia / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
metabolic acidosis / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known

fever / Early / 60.0-69.0
weakness / Early / 9.0-65.0
infection / Delayed / 33.0-44.0
cough / Delayed / 10.0-44.0
fatigue / Early / 10.0-38.0
nausea / Early / 31.0-36.0
vomiting / Early / 31.0-36.0
anorexia / Delayed / 7.0-34.0
chills / Rapid / 11.0-19.0
myalgia / Early / 4.0-16.0
diarrhea / Early / 13.0-15.0
rash / Early / 15.0-15.0
diaphoresis / Early / 1.0-13.0
paresthesias / Delayed / 4.0-12.0
pharyngitis / Delayed / 0-9.0
malaise / Early / 6.0-8.0
sinusitis / Delayed / 0-5.0
headache / Early / 0-3.0
alopecia / Delayed / 0-3.0
pruritus / Rapid / 1.0-3.0
epistaxis / Delayed / 0-1.0
seborrhea / Delayed / 0-1.0
arthralgia / Delayed / 0-1.0
purpura / Delayed / Incidence not known
agitation / Early / Incidence not known

Bone marrow suppression such as severe anemia, neutropenia, and thrombocytopenia and pancytopenia resulting in death has been reported with fludarabine therapy; toxicity is cumulative and typically reversible. Clinically significant cytopenias may last from about 2 months to 1 year. Monitor complete blood counts prior to and periodically during treatment with fludarabine; therapy delay or a dosage reduction may be necessary in patients who develop myelosuppression. Fludarabine administration requires an experienced clinician knowledgeable in the use of antineoplastic therapy.[64041] [64042]

Severe dose-dependent neurotoxicity has been reported with fludarabine therapy. High-dose fludarabine (approximately 4-times more than the recommended CLL dose) resulted in vision loss, coma, and death. Additionally, central nervous system toxicity (e.g., coma, seizures, agitation, and confusion) has occurred in CLL patients treated at the recommended fludarabine dosage. Monitor patients for signs and symptoms of neurotoxicity; therapy delay, a dose reduction, or discontinuation may be necessary in patients who develop neurologic toxicity. Due to the risk of fatigue, confusion, and visual disturbance, patients should use caution when driving or operating machinery.[64041] [64042]

A high rate of fatal pulmonary toxicity occurred in patients with CLL who received fludarabine in combination with pentostatin (off-label use) in a clinical study; therefore, use with pentostatin is not recommended.

Life-threatening and sometimes fatal autoimmune disease (e.g., hemolytic anemia, immune thrombocytopenic purpura (ITP), Evans syndrome, and acquired hemophilia) has been reported with fludarabine therapy. Monitor patients closely for signs or symptoms of hemolysis (e. g., reticulocyte count, indirect bilirubin level, LDH level).[64041] [64042]

Fludara

Rx

Purine nucleoside antineoplastic agent
Used for the treatment of adult patients with B-cell chronic lymphocytic leukemia who have not responded to or whose disease has progressed during treatment with at least 1 standard alkylating agent-containing regimen
Life-threatening or fatal autoimmune reactions have been reported; monitor for hemolysis

25 mg/m2 IV once daily on days 1, 2, 3, 4, and 5 repeated every 28 days for up to 3 cycles past the achievement of maximal response. Therapy delay, dose reduction, or discontinuation may be necessary in patients who develop toxicity.[64042]

Dosage not established. Severe and life-threatening adverse effects were reported more often with fludarabine plus chlorambucil compared with fludarabine alone in patients with previously untreated CLL in a randomized, 3-arm, phase 3 trial. There is not sufficient evidence to support the use of this drug combination for this indication.

25 mg/m2 IV daily on days 1, 2, 3, 4, and 5 repeated every 28 days for 6 cycles followed by rituximab 375 mg/m2 IV for 4 weekly doses in patients with stable disease or better after 2 months of observation (sequential therapy) or fludarabine 25 mg/m2 IV daily on days 1, 2, 3, 4, and 5 repeated every 28 days for 6 cycles with rituximab 375 mg/m2 IV on day 1 and 4 on cycle 1 then 375 mg/m2 IV on day 1 only on cycles 2 to 6 concurrently followed by rituximab 375 mg/m2 IV for 4 weekly doses in patients who had stable disease or better 2 months after therapy (concurrent therapy) was studied in 104 patients in a randomized, noncomparative, phase 2 trial. Because the first 44 patients treated with concurrent therapy experienced infusion-related adverse effects, the last 7 patients received stepped up therapy on cycle 1 with rituximab.[27293] [46762]

25 mg/m2 IV daily on days 1, 2, and 3 plus cyclophosphamide 250 mg/m2 IV daily on days 1, 2, and 3 repeated every 28 days for up to 6 cycles was evaluated in a randomized, phase 3 studies.[50268] [41970] In one study, patients with severe lymphopenia for more than 7 days received prophylactic antibiotics.[41970] In another study, patients received prophylactic antibiotic therapy with cotrimoxazole for 6 months after treatment and allopurinol daily for 7 days during the first 2 to 3 courses; prophylactic antiviral therapy was recommended.[50268]

24 mg/m2 orally daily on days 1, 2, 3, 4, and 5 plus cyclophosphamide 150 mg/m2 orally daily on days 1, 2, 3, 4, and 5 repeated every month for up to 6 cycles was evaluated in a randomized, phase 3 study. Patients received prophylactic antibiotic therapy with cotrimoxazole for 6 months after treatment and allopurinol daily for 7 days during the first 2 to 3 courses; prophylactic antiviral therapy was recommended.[50268] No significant differences in efficacy were found between patients who received oral or IV fludarabine plus cyclophosphamide therapy in a retrospective analysis in 65 patients.[50269]

25 mg/m2 IV daily on days 1, 2, and 3 plus cyclophosphamide 250 mg/m2 daily on days 1, 2, and 3 (FC regimen) and rituximab 375 mg/m2 IV on day 0 (the day prior to FC) on cycle 1, then rituximab 500 mg/m2 IV on day 1 on cycles 2 to 6 repeated every 28 days (R-FC regimen) for 6 cycles has been studied in randomized, phase 3 trials. Treatment with R-FC (mean of 5.2 cycles) resulted in a significantly improved progression-free survival (PFS) time (primary endpoint) compared with FC alone (51.8 vs. 32.8 months; p less than 0.0001) in 817 previously untreated CLL patients in a multinational, randomized, phase 3 trial. The 3-year PFS (65% vs. 45% hazard ratio (HR) = 0.56; 95% CI, 0.46 to 0.69) and overall survival (OS) (87% vs. 83%; HR = 0.67; 95% CI, 0.48 to 0.92) rates were also significantly improved with R-FC.[41970] The median PFS time (primary endpoint) was 30.6 months with R-FC compared with 20.6 months with FC (HR = 0.65; 95% CI, 0.51 to 0.82; p less than 0.001) in another multinational, randomized, phase 3trial in 552 CLL patients who had relapsed or refractory disease following 1 prior line of therapy. All patients in this study received tumor lysis and antibiotic/antiviral prophylaxis. At a median follow-up time of 25 months, the median OS was not significantly different between treatment arms (R-FC, median time not reached; FC, 52 months).[40235]

30 mg/m2 IV daily on days 1, 2, and 3 in combination with alemtuzumab 30 mg IV daily on days 1, 2, and 3 repeated every 28 days for up to 6 cycles has been studied in a randomized, phase 3 trial. Alemtuzumab was titrated to 30 mg on the first cycle of treatment as follows: 3 mg IV over 2 hours on day 1, 10 mg IV over 2 hours on day 2, 30 mg IV over 2 hours on day 3. The same dose was repeated daily if grade 3 or 4 infusion-related toxicity occurred until it was well tolerated (grade 2 or lower toxicity) with appropriate premedication; a maximum of 14 days was allowed for titration to 30 mg. After escalation, fludarabine was administered first followed by alemtuzumab IV over 4 to 6 hours on the first day of each cycle and over 2 hours on days 2 and 3. All patients received acetaminophen and an antihistamine 30 minute prior to each alemtuzumab infusion and hydrocortisone 100 mg IV (or equivalent) prior to each alemtuzumab infusion during the dose escalation phase and then on day 1 of each subsequent cycles. Patients also received prophylaxis with co-trimoxazole (or equivalent) and famciclovir starting at the beginning of therapy and continuing until CD4 counts were at least 200 cells/microL.[55832]

30 mg/m2/day IV over 30 minutes for 5 days repeated every 4 weeks has been studied in patients with prolymphocytic leukemia. Some patients also received prednisone 60 mg/m2/day PO for 5 days repeated every 4 weeks; however, overall response rates did not appear improved with combination therapy compared with fludarabine alone.

25 mg/m2 IV daily on days 1, 2, and 3 in combination with mitoxantrone 10 mg/m2 IV on day 1 and rituximab 375 mg/m2 IV on day 1 repeated every 21 days for 6 cycles followed by 2 additional rituximab 375 mg/m2 IV doses given at 21-day intervals has been evaluated in patients with previously untreated follicular lymphoma in a randomized, phase III trial.

30 mg/m2 IV over 30 minutes on days 1—5, followed 3.5 hours later each day by cytarabine 2 g/m2 IV over 4 hours on days 1—5 and G-CSF (filgrastim or lenograstim) 5 mcg/kg from day 0 (24 hours before starting chemotherapy) until the ANC > 500/mm3.

Fludarabine 30 mg/m2/day IV for 5 consecutive days (days -7 to -3) in combination with cyclophosphamide 1 g/m2/day IV on 3 consecutive days (days -5 to -3). Low dose methotrexate was given in combination with tacrolimus or cyclosporine for the prevention of graft-versus-host-disease. Infection prophylaxis with fluconazole, acyclovir, and TMP/SMX was given per institutional standards.

Cyclophosphamide 60 mg/kg/day IV on 2 consecutive days (days -7 and -6) in combination with fludarabine 25 mg/m2/day IV for 5 consecutive days (days -5 to -1). Cyclosporine alone or in combination with mycophenolate was used for GVHD prevention. For obese patients (> 120% ideal body weight), chemotherapy dosing weight was calculated by using the formula: dosing weight = ideal body weight + (actual/ideal weight)/2.

25 mg/m2/day IV for 5 days repeated every 28 days has been evaluated in clinical trials; overall response rates ranged from 19% to 29.5%. In a nonrandomized study, treatment was continued for a mean of 5 cycles (range, 2—8 cycles) and 43.2% of patients received extracorporeal photochemotherapy (ECP) after fludarabine.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Creatinine clearance (CrCl) of 50 to 79 mL/min: Reduce initial dose to 20 mg/m2 IV daily for 5 days.CrCl of 30 to 49 mL/min: Reduce initial dose to 15 mg/m2 IV daily for 5 days.CrCl less than 30 mL/min: Use not recommended.[64041]
Alternatively, reduce the initial dose by 20% in patients with CrCL of 30 to 70 mL/min; do not administer in patients with CrCl less than 30 mL/min.[64042]

Albuterol; Budesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Azelastine; Fluticasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Basiliximab: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents may result in additive effects. A dosage reduction of the purine analog may be indicated when used in combination with other myelosuppressive chemotherapy.
Beclomethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Betamethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide; Formoterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Corticosteroids: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Cyclosporine: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as immunosuppressives may result in additive effects. A dosage reduction of the antineoplastic may be indicated when used in combination with other myelosuppressive chemotherapy.
Cytarabine, ARA-C: (Minor) Prior or concurrent administration of cytarabine, ARA-C with fludarabine results in inhibition of the metabolism of fludarabine to its active triphosphate. Fludarabine administration should generally precede cytarabine, ARA-C administration.
Deflazacort: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Dexamethasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fludrocortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Flunisolide: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Salmeterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Fluticasone; Vilanterol: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Formoterol; Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Hydrocortisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Intranasal Influenza Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Methylprednisolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Olopatadine; Mometasone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Pentostatin: (Contraindicated) The combined use of pentostatin and fludarabine phosphate is not recommended because it may be associated with an increased risk of fatal pulmonary toxicity. A boxed warning about this potentially fatal interaction exists in the product label. In a clinical investigation in patients with refractory chronic lymphocytic leukemia using pentostatin at the recommended dose in combination with fludarabine phosphate, 4 of 6 patients entered in the study had severe or fatal pulmonary toxicity.
Pentoxifylline: (Minor) Additive cytotoxic effects of fludarabine may be seen when the drug is given in combination with pentoxyfylline. Pentoxifylline disrupts DNA repair mechanisms by preventing cell cycle arrest at the G2/M checkpoint. By not allowing DNA repair, pentoxifylline is thought to increase fludarabine-induced cytotoxicity.
Platelet Inhibitors: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
Prednisolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Prednisone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Rotavirus Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Triamcinolone: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Typhoid Vaccine: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Yellow Fever Vaccine, Live: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

Fludara/Fludarabine/Fludarabine Phosphate Intravenous Inj Pwd F/Sol: 50mg
Fludarabine/Fludarabine Phosphate Intravenous Inj Sol: 1mL, 25mg

25 mg/m2 IV daily for 5 days repeated every 28 days; 30 mg/m2 IV daily for 5 days has been studied for off-label uses.

25 mg/m2 IV daily for 5 days repeated every 28 days; 30 mg/m2 IV daily for 5 days has been studied for off-label uses.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Fludarabine acts as a cytotoxic purine antimetabolite. Upon administration, fludarabine is rapidly dephosphorylated in the plasma to free nucleoside 9-beta-D-arabinosyl-2 fluoroadenine (F-ara-A), which then enters into the cell via high and low affinity transport systems. The rate of transport of fludarabine into malignant cells is greater than that into normal cells. Intracellularly, F-ara-A is converted to the 5'-triphosphate, F-ara-ATP. The rate limiting step in this process is the formation of the monophosphate, which is catalyzed by deoxycytidine kinase. Cells that lack deoxycytidine kinase are resistant to fludarabine. The cytotoxicity of F-ara-ATP is primarily due to its effects on DNA. F-ara-ATP competes with deoxyadenosine triphosphate for incorporation into DNA. Once incorporated into DNA, F-ara-ATP functions as a DNA chain terminator, preventing the elongation of DNA strands at the 3'-terminal. F-ara-ATP also inhibits DNA repair by specifically inhibiting DNA polymerase alpha, gamma, and delta.
 
In addition, F-ara-ATP decreases deoxynucleotide pools by inhibiting ribonucleoside diphosphate reductase. By decreasing deoxynucleotide pools, fludarabine enhances the activity of deoxycytidine kinase, the enzyme required for phosphorylation of F-ara-A. F-ara-A also inhibits DNA primase and DNA ligase I resulting in DNA deletions and mutations. Incorporation into RNA and inhibition of RNA transcription occurs leading to decreased mRNA and protein production, and may be relevant to the activity of fludarabine in indolent diseases. However, 10-fold higher intracellular concentrations are required to inhibit DNA versus RNA. Fludarabine depletes CD4+ cells leading to immunosuppression. Combination chemotherapy regimens have been designed to enhance the cytotoxicity of fludarabine by enhancing the accumulation of the triphosphate form or by combining fludarabine with DNA damaging agents that inhibit DNA repair mechanisms.

Fludarabine is administered intravenously or orally.

Pharmacokinetic studies of the oral form have demonstrated an oral bioavailability of 50—65%; similar systemic exposure is observed after a single oral dose of fludarabine 40 mg/m2 and a single intravenous dose of fludarabine 25 mg/m2. The time to Cmax and bioavailability were dose independent. The oral bioavailability of fludarabine is unaffected by food.

The intravenous formulation is administered as the monophosphate salt, which increases the drug's solubility. Following IV infusion, rapid dephosphorylation of fludarabine phosphate to the active metabolite 2-fluoro-ara-A (F-ara-A) occurs. This dephosphorylation of fludarabine phosphate is so rapid that within minutes the parent drug is undetectable in plasma. Fludarabine is widely distributed and bound to body tissues. A biphasic decline in F-ara-A plasma levels has been described with a terminal elimination half-life of 7—12 hours. The intracellular half-life of F-ara-ATP is about 15 hours. Moderate accumulation of F-ara-A has been shown following 5 daily doses. During a 5-day treatment, F-ara-A trough plasma levels increased by a factor of 2. F-ara-A is excreted primarily in the urine. The rate of fludarabine total body clearance correlates closely with creatinine clearance. Renal clearance represents about 40% of total body clearance. The severity of fludarabine-induced neutropenia is directly related to total body clearance, AUC, and half-life.

Fludarabine is classified as FDA pregnancy risk category D.[64041] It may cause fetal harm when administered to a pregnant woman based on its mechanism of action and data from animal studies; therefore, females of reproductive potential who are receiving fludarabine should avoid pregnancy. Advise pregnant women of the potential risk to the fetus with fludarabine therapy. Fludarabine was embryolethal and teratogenic in rats and rabbits in animal studies.[64041] [64042]

It is not known if fludarabine is secreted in human milk. Due to the potential for serious adverse reactions in nursing infants including tumorigenicity, breast-feeding is not recommended during fludarabine therapy.[64041] [64042]