Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1134
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Fludarabine Phosphate (Injection, Powder, Lyophilized, For Solution)
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Usual Dose: The recommended adult dose of Fludarabine Phosphate for
Injection, USP is 25 mg/madministered intravenously over
a period of approximately 30 minutes daily for five consecutive days.
Each 5 day course of treatment should commence every 28 days. Dosage
may be decreased or delayed based on evidence of hematologic or nonhematologic
toxicity. Physicians should consider delaying or discontinuing the
drugif neurotoxicity occurs. A number of clinical
settings may predispose to increased toxicity from fludarabine phosphate,
USP. These include advanced age, renal insufficiency, and bone marrow
impairment. Such patients should be monitored closely for excessive
toxicity and the dose modified accordingly. The optimal duration of treatment has not been clearly established.
It is recommended that three additional cycles of fludarabine phosphate,
USP be administered following the achievement of a maximal response
and then the drug should be discontinued. Renal Insufficiency Adult patients with moderate impairment of renal function (creatinine
clearance 30 to 70 mL/min/1.73 m) should have a 20% dose
reduction of fludarabine phosphate, USP. Fludarabine phosphate, USP
should not be administered to patients with severely impaired renal
function (creatinine clearance less than 30 mL/min/1.73 m). Preparation of
Solutions: Fludarabine Phosphate for
Injection, USP should be prepared for parenteral use by aseptically
adding Sterile Water for Injection, USP. When reconstituted with 2
mL of Sterile Water for Injection, USP, the solid cake should fully
dissolve in 15 seconds or less; each mL of the resulting solution
will contain 25 mg of fludarabine phosphate, USP, 25 mg of mannitol,
and sodium hydroxide to adjust the pH to 7.7. The pH range for the
final product is 7.2 to 8.2. In clinical studies, the product has
been diluted in 100 cc or 125 cc of 5% Dextrose Injection, USP or
0.9% Sodium Chloride, USP. Reconstituted Fludarabine
Phosphate for Injection, USP contains no antimicrobial preservative
and thus should be used within 8 hours of reconstitution. Care must
be taken to assure the sterility of prepared solutions. Parenteral
drug products should be inspected visually for particulate matter
and discoloration prior to administration. Fludarabine
Phosphate for Injection, USP should not be mixed with other drugs. Handling and Disposal: Procedures for proper handling and disposal
should be considered. Consideration should be given to handling and
disposal according to guidelines issued for cytotoxic drugs. Several
guidelines on this subject have been published.There
is no general agreement that all of the procedures recommended in
the guidelines are necessary or appropriate. Caution should be exercised in the handling and preparation of Fludarabine
Phosphate for Injection, USP solution. The use of latex gloves and
safety glasses is recommended to avoid exposure in case of breakage
of the vial or other accidental spillage. If the solution contacts
the skin or mucous membranes, wash thoroughly with soap and water;
rinse eyes thoroughly with plain water. Avoid exposure by inhalation
or by direct contact of the skin or mucous membranes. Fludarabine Phosphate for Injection, USP should not be handled by
pregnant staff.
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Fludarabine Phosphate for Injection, USP contains
fludarabine phosphate, USP, a fluorinated nucleotide analog of the
antiviral agent vidarabine, 9-��-D-arabinofuranosyladenine (ara-A)
that is relatively resistant to deamination by adenosine deaminase.
Each vial of sterile lyophilized solid cake contains 50 mg of the
active ingredient fludarabine phosphate, USP, 50 mg of mannitol, and
sodium hydroxide to adjust pH to 7.7. The pH range for the final product
is 7.2 to 8.2. Reconstitution with 2 mL of Sterile Water for Injection,
USP results in a solution containing 25 mg/mL of fludarabine phosphate,
USP intended for intravenous administration. The chemical name for fludarabine phosphate, USP is 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-��-D-arabinofuranosyl)(2-fluoro-ara-AMP).
The molecular formula of fludarabine phosphate, USP is CHFNOP (MW 365.2) and the structure
is:
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Fludarabine phosphate, USP is rapidly dephosphorylated
to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine
kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite
appears to act by inhibiting DNA polymerase alpha, ribonucleotide
reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism
of action of this antimetabolite is not completely characterized and
may be multi-faceted. Phase I studies in humans
have demonstrated that fludarabine phosphate, USP is rapidly converted
to the active metabolite, 2-fluoro-ara-A, within minutes after intravenous
infusion. Consequently, clinical pharmacology studies have focused
on 2-fluoro-ara-A pharmacokinetics. After the five daily doses of
25 mg 2-fluoro-ara-AMP/mto cancer patients infused over
30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation.
During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels
increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A
was estimated as approximately 20 hours. In vitro, plasma protein binding of fludarabine ranged
between 19% and 29%. A correlation was noted
between the degree of absolute granulocyte count nadir and increased
area under the concentration x time curve (AUC). Special Populations Pediatric Patients Limited pharmacokinetic data for fludarabine
phosphate, USP are available from a published study of children (ages
1 to 21 years) with refractory acute leukemias or solid tumors (Children's
Cancer Group Study 097). When fludarabine phosphate, USP
was administered as a loading dose over 10 minutes immediately followed
by a 5-day continuous infusion, steady-state conditions were reached
early. Patients with
Renal Impairment The total body clearance
of the principal metabolite 2-fluoro-ara-A correlated with the creatinine
clearance, indicating the importance of the renal excretion pathway
for the elimination of the drug. Renal clearance represents approximately
40% of the total body clearance. Patients with moderate renal impairment
(17 to 41 mL/min/m) receiving 20% reduced fludarabine
phosphate, USP dose had a similar exposure (AUC; 21 versus 20 nM���h/mL)
compared to patients with normal renal function receiving the recommended
dose. The mean total body clearance was 172 mL/min for normal and
124 mL/min for patients with moderately impaired renal function. Clinical Studies Two single-arm open-label studies of fludarabine phosphate,
USP have been conducted in adult patients with CLL refractory to at
least one prior standard alkylating-agent containing regimen. In a
study conducted by M.D. Anderson Cancer Center (MDAH), 48 patients
were treated with a dose of 22 to 40 mg/mdaily for 5
days every 28 days. Another study conducted by the Southwest Oncology
Group (SWOG) involved 31 patients treated with a dose of 15 to 25
mg/mdaily for 5 days every 28 days. The overall objective
response rates were 48% and 32% in the MDAH and SWOG studies, respectively.
The complete response rate in both studies was 13%; the partial response
rate was 35% in the MDAH study and 19% in the SWOG study. These response
rates were obtained using standardized response criteria developed
by the National Cancer Institute CLL Working Groupand
were achieved in heavily pre-treated patients. The ability of fludarabine
phosphate, USP to induce a significant rate of response in refractory
patients suggests minimal cross-resistance with commonly used anti-CLL
agents. The median time to response in the MDAH
and SWOG studies was 7 weeks (range of 1 to 68 weeks) and 21 weeks
(range of 1 to 53 weeks) respectively. The median duration of disease
control was 91 weeks (MDAH) and 65 weeks (SWOG). The median survival
of all refractory CLL patients treated with fludarabine phosphate,
USP was 43 weeks and 52 weeks in the MDAH and SWOG studies, respectively. Rai stage improved to Stage II or better in 7 of 12 MDAH
responders (58%) and in 5 of 7 SWOG responders (71%) who were Stage
III or IV at baseline. In the combined studies, mean hemoglobin concentration
improved from 9.0 g/dL at baseline to 11.8 g/dL at the time of response
in a subgroup of anemic patients. Similarly, average platelet count
improved from 63,500/mmto 103,300/mmat the
time of response in a subgroup of patients who were thrombocytopenic
at baseline.
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Fludarabine phosphate, USP is contraindicated in
those patients who are hypersensitive to this drug or its components.
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Fludarabine Phosphate for Injection, USP is supplied
as a white, lyophilized solid cake. Each vial contains 50 mg of fludarabine
phosphate, USP, 50 mg of mannitol, and sodium hydroxide to adjust
pH to 7.7. The pH range for the final product is 7.2 to 8.2. Store
at 20 to 25��C (68 to 77��F). [See USP Controlled Room Temperature.]
Store upright. Fludarabine Phosphate for Injection,
USP is supplied in a clear glass single dose vial and cartoned individually. NDC 61703-344-18
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WARNING: Fludarabine
Phosphate for Injection, USP should be administered under the supervision
of a qualified physician experienced in the use of antineoplastic
therapy. Fludarabine Phosphate for Injection, USP can severely suppress
bone marrow function. When used at high doses in dose-ranging studies
in patients with acute leukemia, Fludarabine Phosphate for Injection,
USP was associated with severe neurologic effects, including blindness,
coma, and death. This severe central nervous system toxicity occurred
in 36% of patients treated with doses approximately four times greater
(96 mg/m/day for 5 to 7 days) than the recommended dose.
Similar severe central nervous system toxicity has been rarely (���0.2%) reported in patients treated at doses in the range of the dose
recommended for chronic lymphocytic leukemia. Instances of life-threatening and sometimes fatal autoimmune phenomena
such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic
purpura (ITP), Evan's syndrome, and acquired hemophilia have
been reported to occur after one or more cycles of treatment with
Fludarabine Phosphate for Injection, USP. Patients undergoing treatment
with Fludarabine Phosphate for Injection, USP should be evaluated
and closely monitored for hemolysis. In a clinical
investigation using Fludarabine Phosphate for Injection, USP in combination
with pentostatin (deoxycoformycin) for the treatment of refractory
chronic lymphocytic leukemia (CLL), there was an unacceptably high
incidence of fatal pulmonary toxicity. Therefore, the use of Fludarabine
Phosphate for Injection, USP in combination with pentostatin is not
recommended.
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General: Fludarabine phosphate, USP is a potent antineoplastic
agent with potentially significant toxic side effects. Patients undergoing
therapy should be closely observed for signs of hematologic and nonhematologic
toxicity. Periodic assessment of peripheral blood counts is recommended
to detect the development of anemia, neutropenia and thrombocytopenia. Tumor lysis syndrome associated with fludarabine phosphate,
USP treatment has been reported in CLL patients with large tumor burdens.
Since fludarabine phosphate, USP can induce a response as early as
the first week of treatment, precautions should be taken in those
patients at risk of developing this complication. In patients with impaired state of health, fludarabine phosphate,
USP should be given with caution and after careful risk/benefit consideration.
This applies especially for patients with severe impairment of bone
marrow function (thrombocytopenia, anemia, and/or granulocytopenia),
immunodeficiency or with a history of opportunistic infection. Prophylactic
treatment should be considered in patients at increased risk of developing
opportunistic infections. There are inadequate
data on dosing of patients with renal insufficiency. Fludarabine phosphate,
USP must be administered cautiously in patients with renal insufficiency.
The total body clearance of 2-fluoro-ara-A has been shown to be directly
correlated with creatinine clearance. Patients with moderate impairment
of renal function (creatinine clearance 30 to 70 mL/min/1.73m) should have their fludarabine dose reduced by 20% and be
monitored closely. Fludarabine is not recommended for patients with
severely impaired renal function (creatinine clearance less than 30 mL/min/1.73
m). Fludarabine phosphate, USP may
reduce the ability to drive or use machines, since fatigue, weakness
and visual disturbances have been observed.<br/>Laboratory Tests: During treatment, the patient's hematologic
profile (particularly neutrophils and platelets) should be monitored
regularly to determine the degree of hematopoietic suppression.<br/>Drug Interactions: The use of fludarabine phosphate, USP in combination
with pentostatin is not recommended due to the risk of severe pulmonary
toxicity (see WARNINGS section). Carcinogenesis No animal carcinogenicity studies with fludarabine
phosphate, USP have been conducted. Mutagenesis Fludarabine
phosphate, USP was not mutagenic to bacteria (Ames test) or mammalian
cells (HGRPT assay in Chinese hamster ovary cells) either in the presence
or absence of metabolic activation. Fludarabine phosphate, USP was
clastogenic in vitro to Chinese
hamster ovary cells (chromosome aberrations in the presence of metabolic
activation) and induced sister chromatid exchanges both with and without
metabolic activation. In addition, fludarabine phosphate, USP was
clastogenic in vivo (mouse
micronucleus assay) but was not mutagenic to germ cells (dominant
lethal test in male mice). Impairment of Fertility Studies in mice, rats and dogs have demonstrated dose-related adverse
effects on the male reproductive system. Observations consisted of
a decrease in mean testicular weights in mice and rats with a trend
toward decreased testicular weights in dogs and degeneration and necrosis
of spermatogenic epithelium of the testes in mice, rats and dogs.
The possible adverse effects on fertility in humans have not been
adequately evaluated.<br/>Pregnancy: Pregnancy Category D: (See WARNINGS section).<br/>Nursing Mothers: It is not known whether this drug is excreted in
human milk. Because many drugs are excreted in human milk and because
of the potential for serious adverse reactions in nursing infants
from fludarabine phosphate, USP, a decision should be made to discontinue
nursing or discontinue the drug, taking into account the importance
of the drug for the mother.<br/>Pediatric Use: Data submitted to the FDA was insufficient to establish
efficacy in any childhood malignancy. Fludarabine was evaluated in
62 pediatric patients (median age 10, range 1 to 21) with refractory
acute leukemia (45 patients) or solid tumors (17 patients). The
fludarabine regimen tested for pediatric acute lymphocytic leukemia
(ALL) patients was a loading bolus of 10.5 mg/m/day followed
by a continuous infusion of 30.5 mg/m/day for 5 days.
In 12 pediatric patients with solid tumors, dose-limiting myelosuppression
was observed with a loading dose of 8 mg/m/day followed
by a continuous infusion of 23.5 mg/m/day for 5 days.
The maximum tolerated dose was a loading dose of 7 mg/m/day followed by a continuous infusion of 20 mg/m/day
for 5 days. Treatment toxicity included bone marrow suppression. Platelet
counts appeared to be more sensitive to the effects of fludarabine
than hemoglobin and white blood cell counts. Other adverse events
included fever, chills, asthenia, rash, nausea, vomiting, diarrhea,
and infection. There were no reported occurrences of peripheral neuropathy
or pulmonary hypersensitivity reaction. Vaccination During
and after treatment with fludarabine phosphate, USP, vaccination with
live vaccines should be avoided. Disease Progression Disease progression and transformation (e.g. Richter's syndrome)
have been reported in CLL patients.
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High doses of fludarabine phosphate, USP (see WARNINGS section) have been associated
with an irreversible central nervous system toxicity characterized
by delayed blindness, coma, and death. High doses are also associated
with severe thrombocytopenia and neutropenia due to bone marrow suppression.
There is no known specific antidote for fludarabine phosphate, USP
overdosage. Treatment consists of drug discontinuation and supportive
therapy.
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Fludarabine Phosphate
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Fludarabine Phosphate (Injection, Powder, Lyophilized, For Solution)
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The most common adverse events include myelosuppression
(neutropenia, thrombocytopenia and anemia), fever and chills, infection,
and nausea and vomiting. Other commonly reported events include malaise,
fatigue, anorexia, and weakness. Serious opportunistic infections
have occurred in CLL patients treated with fludarabine phosphate,
USP. Adverse events, and those reactions which are more clearly related
to the drug are arranged below according to body system. Hematopoietic Systems: Hematologic events (neutropenia, thrombocytopenia, and/or anemia)
were reported in the majority of CLL patients treated with fludarabine
phosphate, USP. During fludarabine phosphate, USP treatment of 133
patients with CLL, the absolute neutrophil count decreased to less
than 500/mmin 59% of patients, hemoglobin decreased from
pretreatment values by at least 2 grams percent in 60%, and platelet
count decreased from pretreatment values by at least 50% in 55%. Myelosuppression
may be severe, cumulative, and may affect multiple cell lines. Bone
marrow fibrosis occurred in one CLL patient treated with fludarabine
phosphate, USP. Several instances of trilineage
bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes
resulting in death, have been reported in postmarketing surveillance.
The duration of clinically significant cytopenia in the reported cases
has ranged from approximately 2 months to approximately 1 year. These
episodes have occurred both in previously treated or untreated patients. Life-threatening and sometimes fatal autoimmune phenomena
such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic
purpura (ITP), Evan's syndrome, and acquired hemophilia have
been reported to occur in patients receiving fludarabine phosphate,
USP (see WARNINGS section). The
majority of patients rechallenged with fludarabine phosphate, USP
developed a recurrence in the hemolytic process. In post-marketing experience, rare cases of myelodysplastic syndrome
and acute myeloid leukemia associated with prior, concomitant or subsequent
treatment with alkylating agents or irradiation have been reported. Infections: Serious,
and sometimes fatal infections, including opportunistic infections
and reactivations of latent viral infections such as VZV (Herpes zoster),
Epstein-Barr virus and JC virus (progressive multifocal leukoencephalopathy)
have been reported in patients treated with fludarabine phosphate,
USP. Rare cases of Epstein Barr Virus (EBV)
associated lymphoproliferative disorders have been reported in patients
treated with fludarabine phosphate, USP. Metabolic: Tumor lysis syndrome has been
reported in CLL patients treated with fludarabine phosphate, USP.
This complication may include hyperuricemia, hyperphosphatemia, hypocalcemia,
metabolic acidosis, hyperkalemia, hematuria, urate crystalluria, and
renal failure. The onset of this syndrome may be heralded by flank
pain and hematuria. Nervous System: (See WARNINGS section) Objective weakness, agitation, confusion, visual disturbances,
optic neuritis, optic neuropathy, blindness and coma have occurred
in CLL patients treated with fludarabine phosphate, USP at the recommended
dose. Peripheral neuropathy has been observed in patients treated
with fludarabine phosphate, USP and one case of wrist-drop was reported. In post-marketing experience, cases of progressive multifocal
leukoencephalopathy have been reported. Most cases had a fatal outcome.
Many of these cases were confounded by prior and/or concurrent chemotherapy.
The time to onset has ranged from a few weeks to approximately one
year after initiating treatment. Pulmonary System: Pneumonia, a frequent
manifestation of infection in CLL patients, occurred in 16%, and 22%
of those treated with fludarabine phosphate, USP in the MDAH and SWOG
studies, respectively. Pulmonary hypersensitivity reactions to fludarabine
phosphate, USP characterized by dyspnea, cough and interstitial pulmonary
infiltrate have been observed. In post-marketing
experience, cases of severe pulmonary toxicity have been observed
with fludarabine use which resulted in ARDS, respiratory distress,
pulmonary hemorrhage, pulmonary fibrosis, and respiratory failure.
After an infectious origin has been excluded, some patients experienced
symptom improvement with corticosteroids. Gastrointestinal System: Gastrointestinal
disturbances such as nausea and vomiting, anorexia, diarrhea, stomatitis,
and gastrointestinal bleeding have been reported in patients treated
with fludarabine phosphate, USP. Cardiovascular: Edema has been frequently
reported. One patient developed a pericardial effusion possibly related
to treatment with fludarabine phosphate, USP. No other severe cardiovascular
events were considered to be drug related. Genitourinary System: Rare cases of hemorrhagic
cystitis have been reported in patients treated with fludarabine phosphate,
USP. Skin: Skin toxicity, consisting primarily of skin rashes, has been reported
in patients treated with fludarabine phosphate, USP. Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis,
and pemphigus have been reported, with fatal outcomes in some cases. Worsening or flare up of pre-existing skin cancer lesions,
as well as new onset of skin cancer, has been reported in patients
during or after treatment with fludarabine phosphate, USP. Data in the following table are derived from the 133 patients
with CLL who received fludarabine phosphate, USP in the MDAH and SWOG
studies. More than 3000 adult patients received fludarabine
phosphate, USP in studies of other leukemias, lymphomas, and other
solid tumors. The spectrum of adverse effects reported in these studies
was consistent with the data presented above.
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(See BOXED WARNINGS) There are clear dose-dependent toxic effects
seen with fludarabine phosphate, USP. Dose levels approximately 4
times greater (96 mg/m/day for 5 to 7 days) than that
recommended for CLL (25 mg/m/day for 5 days) were associated
with a syndrome characterized by delayed blindness, coma and death.
Symptoms appeared from 21 to 60 days following the last dose.
Thirteen of 36 patients (36%) who received fludarabine phosphate,
USP at high doses (96 mg/m/day for 5 to 7 days) developed
this severe neurotoxicity. This syndrome has been reported rarely
in patients treated with doses in the range of the recommended CLL
dose of 25 mg/m/day for 5 days every 28 days. The effect
of chronic administration of fludarabine phosphate, USP on the central
nervous system is unknown; however, patients have received the recommended
dose for up to 15 courses of therapy. Severe
bone marrow suppression, notably anemia, thrombocytopenia and neutropenia,
has been reported in patients treated with fludarabine phosphate,
USP. In a Phase I study in adult solid tumor patients, the median
time to nadir counts was 13 days (range, 3 to 25 days) for granulocytes
and 16 days (range, 2 to 32)for platelets. Most patients had hematologic
impairment at baseline either as a result of disease or as a result
of prior myelosuppressive therapy. Cumulative myelosuppression may
be seen. While chemotherapy-induced myelosuppression is often reversible,
administration of fludarabine phosphate, USP requires careful hematologic
monitoring. Several instances of trilineage
bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes
resulting in death, have been reported in adult patients. The duration
of clinically significant cytopenia in the reported cases has ranged
from approximately 2 months to approximately 1 year. These episodes
have occurred both in previously treated or untreated patients. Instances of life-threatening and sometimes fatal autoimmune
phenomena such as hemolytic anemia, autoimmune thrombocytopenia/thrombocytopenic
purpura (ITP), Evan's syndrome, and acquired hemophilia have
been reported to occur after one or more cycles of treatment with
fludarabine phosphate, USP in patients with or without a previous
history of autoimmune hemolytic anemia or a positive Coombs'
test and who may or may not be in remission from their disease. Steroids
may or may not be effective in controlling these hemolytic episodes.
The majority of patients rechallenged with fludarabine phosphate,
USP developed a recurrence in the hemolytic process. The mechanism(s)
which predispose patients to the development of this complication
has not been identified. Patients undergoing treatment with fludarabine
phosphate, USP should be evaluated and closely monitored for hemolysis.
Discontinuation of therapy with fludarabine phosphate, USP is recommended
in case of hemolysis. Transfusion-associated
graft-versus-host disease has been observed after transfusion of non-irradiated
blood in fludarabine phosphate, USP treated patients. Fatal outcome
as a consequence of this disease has been reported. Therefore, to
minimize the risk of transfusion-associated graft-versus-host disease,
patients who require blood transfusion and who are undergoing, or
who have received, treatment with fludarabine phosphate, USP should
receive irradiated blood only. In a clinical
investigation using fludarabine phosphate, USP in combination with
pentostatin (deoxycoformycin) for the treatment of refractory chronic
lymphocytic leukemia (CLL) in adults, there was an unacceptably high
incidence of fatal pulmonary toxicity. Therefore, the use of fludarabine
phosphate,USP in combination with pentostatin is not recommended. Of the 133 adult CLL patients in the two trials, there
were 29 fatalities during study. Approximately 50% of the fatalities
were due to infection and 25% due to progressive disease. Pregnancy Category D: Fludarabine phosphate, USP may cause fetal harm when administered
to a pregnant woman. Fludarabine phosphate, USP was teratogenic in
rats and in rabbits. Fludarabine phosphate, USP was administered intravenously
at doses of 0, 1, 10 or 30 mg/kg/day to pregnant rats on days 6 to
15 of gestation. At 10 and 30 mg/kg/day in rats, there was an increased
incidence of various skeletal malformations. Fludarabine phosphate,
USP was administered intravenously at doses of 0, 1, 5 or 8 mg/kg/day
to pregnant rabbits on days 6 to 15 of gestation. Dose-related teratogenic
effects manifested by external deformities and skeletal malformations
were observed in the rabbits at 5 and 8 mg/kg/day. Drug-related deaths
or toxic effects on maternal and fetal weights were not observed.
There are no adequate and well-controlled studies in pregnant women. If fludarabine phosphate, USP is used during pregnancy,
or if the patient becomes pregnant while taking this drug, the patient
should be apprised of the potential hazard to the fetus. Women of
childbearing potential or fertile males must take contraceptive measures
during and at least for 6 months after cessation of therapy.
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Fludarabine Phosphate for Injection, USP 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. The safety and effectiveness of fludarabine phosphate, USP
in previously untreated or non-refractory patients with CLL have not
been established.
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Fludarabine Phosphate
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