Drugs Details

Drugs Info of Oforta
Drugs Details
  • Drugs Type  : Multum
  • Date : 23rd Feb 2015 05:00 am
  • Brand Name : Oforta
  • Generic Name :  fludarabine (oral) (Pronunciation: floo DAR a been)
Descriptions

The chemical name for fludarabine phosphate is 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-β-D-arabinofuranosyl)(2-fluoro-ara-AMP). The molecular formula of fludarabine phosphate is C10H13FN5O7P (MW 365.2) and the structure is provided in Figure 1

Figure 1: Chemical Structure of Fludarabine Phosphate

Oforta (fludarabine phosphate) structural formula illustration

Oforta™ (fludarabine phosphate tablets) for oral administration contain fludarabine phosphate, a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-beta -D-arabinofuranosyladenine (ara-A) that is relatively resistant to deamination by adenosine deaminase. Each tablet contains 10 mg of the active ingredient fludarabine phosphate. The tablet core consists of microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silicon dioxide, croscarmellose sodium and magnesium stearate. The film-coat contains hypromellose, talc, titanium dioxide (E171) and ferric oxide pigment (red/E172, yellow/E172).

What are the possible side effects of fludarabine (Oforta)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pale or yellowed skin, dark colored urine;
  • fast or slow heart rate, weak pulse, trouble concentrating, feeling tired or short of breath;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat,...

Read All Potential Side Effects and See Pictures of Oforta »

What are the precautions when taking fludarabine phosphate tablets (Oforta)?

Before using fludarabine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: hemolytic anemia, severe kidney disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: current infections, certain infections (opportunistic infections such as fungal infections), certain virus conditions (herpes, chickenpox), blood disorders (e.g., anemia, clotting problems), immune system problems, kidney problems,...

Read All Potential Precautions of Oforta »


This monograph has been modified to include the generic and brand name in many instances.

 

Indications

Oforta™ (fludarabine phosphate tablets) for oral use is indicated as a single agent for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) whose disease has not responded to or has progressed during or after treatment with at least one standard alkylating-agent containing regimen. Studies demonstrating clinical benefit such as prolongation of survival or relief of symptoms have not been performed. Studies providing a direct comparison of the clinical efficacy and safety of Oforta™ relative to intravenously administered fludarabine phosphate have not been performed.

Dosage Administration

Chronic Lymphocytic Leukemia (CLL)

The oral dose of Oforta™ is different than the intravenous fludarabine phosphate dose.

The recommended adult dose of Oforta™ (fludarabine phosphate tablets) is 40 mg/m administered by mouth 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 drug if neurotoxicity occurs. Oforta™ (fludarabine phosphate tablets) can be taken either on an empty stomach or with food. The tablets have to be swallowed whole with water; they should not be chewed or broken.

The following table provides guidance for determining the number of tablets of Oforta™ (fludarabine phosphate tablets) to be administered based on body surface area (BSA):

TABLE 1: SUGGESTED NUMBER OF TABLETS TO BE ADMINISTERED

Body Surface Area (BSA) Calculated Total Dose Equivalent to 40 mg/m2 BSA (rounded up or down to nearest 10 mg) Total Number of Tablets
0.75 - 0.88 30 mg 3
0.89 - 1.13 40 mg 4
1.14 - 1.38 50 mg 5
1.39 - 1.63 60 mg 6
1.64 - 1.88 70 mg 7
1.89 - 2.13 80 mg 8
2.14 - 2.38 90 mg 9
2.39 - 2.50 100 mg 10

A number of clinical settings may predispose to increased toxicity from Oforta™ (fludarabine phosphate tablets) . 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 Oforta™ (fludarabine phosphate tablets) be administered following the achievement of a maximal response and then the drug should be discontinued.

Renal Impairment

  • Reduce dose by 20% in patients with mild to moderate renal impairment (creatinine clearance 30 to 70 mL/min/1.73 m ). [See WARNINGS AND PRECAUTIONS]
  • Reduce dose by 50% in patients with severe renal impairment (creatinine clearance < 30 mL/min/1.73 m ). [See WARNINGS AND PRECAUTIONS]

How Supplied

Dosage Forms And Strengths

10 mg tablets that are capsule shaped and salmon pink in color, marked on one side with 'LN' in a regular hexagon.

Storage And Handling

Oforta™ (fludarabine phosphate tablets) is supplied in 10 milligram tablets that are film-coated, capsule shaped, salmon pink in color, and marked on one side with 'LN' in a regular hexagon. Each film-coated tablet contains 10 mg fludarabine phosphate. The tablets are supplied in blisters, each blister strip containing 5 tablets. Packages of 15 and 20 tablets are available in child-resistant containers.

NDC 0024-5820-15: 15 - 10 milligram film-coated tablets per container. Each film-coated tablet is packaged in an individual blister package; 5 tablets per blister strip; 3 blister strips packaged in a plastic bottle with a child-resistant container closure; each bottle is packaged in an individual chip-board carton.

NDC 0024-5820-20: 20 - 10 milligram film-coated tablets per container. Each film-coated tablet is packaged in an individual blister package; 5 tablets per blister strip; 4 blister strips packaged in a plastic bottle with a child-resistant container closure; each bottle is packaged in an individual chip-board carton.

Storage

Store under normal lighting conditions at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP controlled room temperature].

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.1-4 Caution should be exercised in the handling of Oforta™ (fludarabine phosphate tablets) . Push tablets through foil to open. Do not remove tablets from individual blisters until immediately prior to taking or administering each scheduled dose. Do not crush tablets. Avoid exposure by direct contact of the skin or mucous membranes or by inhalation. If contact occurs, wash thoroughly with soap and water or wash the eyes immediately with gently flowing water for at least 15 minutes. Consult healthcare provider in case of a skin reaction or if the drug gets in the eyes.

Manufactured for: sanofi-aventis U.S. LLC, Bridgewater, NJ 08807


This monograph has been modified to include the generic and brand name in many instances.

 

Side Effects

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to Oforta™ (fludarabine phosphate tablets) in 159 patients exposed to the drug. Oforta™ (fludarabine phosphate tablets) was studied primarily in Study 1 in 78 patients with CLL who received prior therapy and in Study 2 in 81 patients with CLL who had not received prior therapy.

Based on experience with the intravenous and oral use of fludarabine phosphate, the most common adverse reactions 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 patients with CLL treated with fludarabine phosphate. The most frequently reported adverse reactions and those reactions which are more clearly related to the drug, as reported in clinical studies conducted with intravenous and oral fludarabine phosphate, are arranged below according to body system.

Hematopoietic Systems

Hematologic events (neutropenia, thrombocytopenia, and/or anemia) were reported in the majority of patients with CLL treated with fludarabine phosphate. During intravenous fludarabine phosphate treatment of 133 patients with CLL, the absolute neutrophil count decreased to less than 500/mm in 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%. Among 78 patients with B-CLL who were treated with Oforta™ (fludarabine phosphate tablets) , the absolute neutrophil count decreased to less than 500/mm in 37% of patients, hemoglobin decreased from pretreatment values by at least 2 grams percent in 14%, and platelet count decreased from pretreatment values by at least 50% in 17% of patients. Myelosuppression may be severe, cumulative, and may affect multiple cell lines. Bone marrow fibrosis occurred in one CLL patient treated with fludarabine phosphate intravenously. In the pivotal oral fludarabine phosphate study (Study 1), there was one report of a non-fatal case of pancytopenia. Similarly, there was one case of non-fatal pancytopenia reported among the 133 patients with CLL treated with intravenous fludarabine phosphate.

Life-threatening and sometimes fatal autoimmune hemolytic anemias have been reported to occur in patients receiving fludarabine phosphate. [See WARNINGS AND PRECAUTIONS] The majority of patients rechallenged with fludarabine phosphate developed a recurrence in the hemolytic process.

Metabolic

Tumor lysis syndrome has been reported in patients with CLL treated with fludarabine phosphate for injection. 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

Objective weakness, agitation, confusion, visual disturbances, and coma< have occurred in patients with CLL treated with fludarabine phosphate at the recommended dose. Peripheral neuropathy and one case of wrist-drop have been observed with intravenous administration of fludarabine phosphate. In Study 1 for Oforta™ (fludarabine phosphate tablets) , there was one report of severe impairment of consciousness that presented concurrent with hemolytic anemia. This patient had enrolled in the study with pre-existing peripheral neurotoxicity. [See WARNINGS AND PRECAUTIONS]

Pulmonary System

Pneumonia, a frequent manifestation of infection in patients with CLL, was observed in two clinical trials conducted with intravenous fludarabine phosphate (16% and 22%) and in two clinical trials with Oforta (fludarabine phosphate tablets) ™ (8% and 3%). Pulmonary hypersensitivity reactions to fludarabine phosphate characterized by dyspnea, cough and interstitial pulmonary infiltrate have been observed. In Study 1 conducted with Oforta™ (fludarabine phosphate tablets) , severe pulmonary toxicity was reported in 5 of 78 patients, often in conjunction with respiratory or pulmonary infections and hence not regarded as isolated drug related pulmonary toxicity.

Gastrointestinal System

Gastrointestinal disturbances such as nausea and vomiting, anorexia, diarrhea, stomatitis and gastrointestinal bleeding have been reported in patients treated with fludarabine phosphate. Nausea and vomiting occurred in up to 38% of patients following treatment with Oforta™ (fludarabine phosphate tablets) in the clinical trials.

Cardiovascular

Edema has been frequently reported. One patient developed a pericardial effusion possibly related to treatment with Oforta™ (fludarabine phosphate tablets) . No other severe cardiovascular events were considered to be drug related.

Genitourinary System

Hemorrhagic cystitis has been reported in patients treated intravenously with fludarabine phosphate.

Skin

Skin toxicity, consisting primarily of skin rashes, has been reported in patients treated with oral and intravenous fludarabine phosphate.

Data in Table 2 are derived from the 159 patients with CLL who received Oforta™ (fludarabine phosphate tablets) in Study 1 and Study 2.

TABLE 2: Incidence (≥ 5%) of Non-Hematologic Adverse Reactions in Patients with CLL Treated with Oforta™ (fludarabine phosphate tablets)

ADVERSE REACTIONS Study 1 Study 2
(N=78) (N=81)
% %
ANY ADVERSE REACTION 82 89
BODY AS A WHOLE 59 77
FEVER 26 11
INFECTION 12 17
PAIN 5 19
FLU SYNDROME 8 5
DIAPHORESIS 8 0
NEUROLOGICAL 19 41
WEAKNESS/FATIGUE (ASTHENIA) 13 31
SWEATING INCREASED 0 14
HEADACHE 9 9
PULMONARY 37 53
COUGH 21 0
COUGH INCREASED 0 6
PNEUMONIA 8 3
DYSPNEA 1 5
SINUSITIS 1 5
UPPER RESPIRATORY INFECTION 9 14
RHINITIS 3 11
BRONCHITIS 6 9
METABOLIC AND NUTRITIONAL 3 31
WEIGHT DECREASED 1 6
LACTIC DEHYDROGENASE INCREASED 0 6
PERIPHERAL EDEMA 0 7
GASTROINTESTINAL 41 28
NAUSEA 5 1
DIARRHEA 6 5
ANOREXIA 19 0
ABDOMINAL PAIN 8 10
CUTANEOUS 22 25
RASH 5 4
SKIN DISORDER 0 6
HERPES SIMPLEX 8 7
GENITOURINARY 8 14
URINARY TRACT INFECTION 4 5
CARDIOVASCULAR 14 17
CHEST PAIN 0 5
MUSCULOSKELETAL 10 19
BACK PAIN 4 9

Post Marketing Experience

The following adverse reactions have been identified during post approval use of Oforta™ (fludarabine phosphate tablets) . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possibly to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hematopoietic Systems

Several instances of trilineage bone marrow hypoplasia or aplasia resulting in pancytopenia, sometimes resulting in death, have been reported in post-marketing 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.

Nervous System

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 median time to onset was approximately one year.

Pulmonary System

In post-marketing experience, cases of severe pulmonary toxicity have been observed with fludarabine phosphate use which resulted in acute respiratory distress syndrome, respiratory distress, pulmonary hemorrhage, pulmonary fibrosis, and respiratory failure. After exclusion of an infectious origin, some patients experienced symptom improvement with corticosteroids.

Read the Oforta (fludarabine phosphate tablets) Side Effects Center for a complete guide to possible side effects

Interactions

Pentostatin

The use of Oforta™ (fludarabine phosphate tablets) in combination with pentostatin is not recommended due to the risk of severe pulmonary toxicity. [See WARNINGS AND PRECAUTIONS]

Read the Oforta Drug Interactions Center for a complete guide to possible interactions

Learn More »


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Neurotoxicity

Dose-dependent neurotoxicity has been observed with fludarabine phosphate. Dose levels approximately 4 times greater (96 mg/m /day for 5 days to 7 days) than the recommended intravenous dose (25 mg/m2/day for 5 days) were associated with a syndrome characterized by delayed blindness, coma and death. Symptoms appeared from 21 days to 60 days following the last dose. Thirteen of 36 patients (36.1%) who received fludarabine phosphate intravenously at high doses ( ≥ 96 mg/m2/day for 5 days to 7 days per course) developed severe neurotoxicity, while only one of 443 patients (0.2%) who received the drug intravenously at low doses ( ≤ 40 mg/m2/day for 5 days per course) developed toxicity. In the pivotal clinical study conducted with Oforta™ (fludarabine phosphate tablets) administered at 40 mg/m2, severe impairment of consciousness was reported in one patient. The effect of chronic administration of fludarabine phosphate on the central nervous system is unknown; however, patients have received the recommended dose for up to 15 courses of therapy. Physicians should consider delaying or discontinuing the drug if neurotoxicity occurs.

Bone Marrow Suppression

Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia, has been reported in patients treated with fludarabine phosphate. In a study in adult solid tumor patients, the median time to nadir counts was 13 days (range, 3 days to 25 days) for granulocytes and 16 days (range, 2 days to 32 days) 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 Oforta™ (fludarabine phosphate tablets) 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. One case of pancytopenia was reported in the pivotal clinical study conducted with Oforta™ (fludarabine phosphate tablets) .

Instances of life-threatening and sometimes fatal autoimmune hemolytic anemia have been reported to occur after one or more cycles of treatment with fludarabine phosphate 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 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 Oforta™ (fludarabine phosphate tablets) should be evaluated and closely monitored for hemolysis.

Pulmonary Toxicity

A high incidence of fatal pulmonary toxicity was observed in a clinical investigation using fludarabine phosphate in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL) in adults. Therefore, the use of Oforta™ (fludarabine phosphate tablets) in combination with pentostatin is not recommended.

Infections

Of 133 adult patients with CLL who received intravenous fludarabine phosphate in two clinical trials, there were 29 fatalities during study. Approximately 50% of the fatalities were due to infection and 25% due to progressive disease. Of 183 adult patients with CLL that received Oforta™ (fludarabine phosphate tablets) in two clinical trials, there were 13 deaths. Approximately 50% of the deaths were due to progressive disease, while two patient deaths (15%) were attributed to infection. Monitor for signs and symptoms of infection.

Tumor Lysis Syndrome

Tumor lysis syndrome associated with fludarabine phosphate treatment has been reported in patients with CLL with large tumor burdens. Since Oforta™ (fludarabine phosphate tablets) 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.

Use of Transfusions

Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of non-irradiated blood in fludarabine phosphate treated patients. Consideration should, therefore, be given to the use of irradiated blood products in those patients requiring transfusions while undergoing treatment with Oforta™ (fludarabine phosphate tablets) .

Renal Impairment

Oforta™ (fludarabine phosphate tablets) must be administered cautiously in patients with renal impairment. Following dosing of the intravenous product, the total body clearance of 2-fluoro-ara-A has been shown to be directly correlated with creatinine clearance. Patients with mild to moderate impairment of renal function (creatinine clearance 30 to 70 mL/min/1.73 m2) should have their Oforta™ (fludarabine phosphate tablets) dose reduced by 20% and be monitored closely. Patients with severe impairment of renal function (creatinine clearance < 30 mL/min/1.73 m2) should have their Oforta™ (fludarabine phosphate tablets) dose reduced by 50% and be monitored closely.

Monitoring

  • Hematologic and Nonhematologic Toxicity

Oforta™ (fludarabine phosphate tablets) is an 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.

  • Hematopoietic Suppression

During treatment, the patient's hematologic profile (particularly neutrophils and platelets) should be monitored regularly to determine the degree of hematopoietic suppression.

  • Infections

Patients treated with Oforta™ (fludarabine phosphate tablets) appear to be at an increased risk of infection. Monitor for signs and symptoms of infection.

Pregnancy

Based on its mechanism of action, Oforta™ (fludarabine phosphate tablets) can cause fetal harm when administered to a pregnant woman. Fludarabine phosphate administered to rats and rabbits during organogenesis caused an increase in resorptions, skeletal and visceral malformation, and decreased fetal body weights. If Oforta™ (fludarabine phosphate tablets) 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 should be advised to avoid becoming pregnant. Women of childbearing potential and fertile males must take contraceptive measures during and at least for 6 months after the cessation of therapy. [see Use in Specific Populations].

Patient Counseling Information

Bone Marrow Suppression

Inform patients that Oforta™ (fludarabine phosphate tablets) decreases blood cell counts such as white blood cells, platelets, and red blood cells. Thus, it is important that periodic assessment of their blood count be performed to detect the development of neutropenia, thrombocytopenia and anemia. [See WARNINGS AND PRECAUTIONS]

Infections

Instruct patients to notify their physician promptly if fever or other signs of infection such as chills, cough, or burning pain on urination occurs while on therapy. [See WARNINGS AND PRECAUTIONS]

Pregnancy

Women of childbearing potential and fertile males must take contraceptive measures during and at least for 6 months after the cessation of therapy. Oforta™ (fludarabine phosphate tablets) may cause fetal harm when administered to a pregnant woman. [See WARNINGS AND PRECAUTIONS]

Handling and Disposal

Instruct patients that caution should be exercised in the handling of Oforta™ (fludarabine phosphate tablets) . Do not crush tablets. Avoid exposure by direct contact of the skin or mucous membranes or by inhalation. If contact occurs, wash thoroughly with soap and water or wash the eyes immediately with gently flowing water for at least 15 minutes. Consult healthcare provider in case of a skin reaction or if the drug gets in the eyes. Ask your healthcare provider or pharmacist for directions about how to safely dispose of Oforta™ (fludarabine phosphate tablets) .

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No animal carcinogenicity studies with Oforta™ (fludarabine phosphate tablets) have been conducted.

Oforta™ is a clastogen.

Fludarabine phosphate was clastogenic in vitro to Chinese hamster ovary cells (chromosome aberration assay) in the presence of metabolic activation and induced sister chromatid exchanges both in the presence and absence of metabolic activation. In addition, fludarabine phosphate was clastogenic in vivo (mouse micronucleus assay) but was not mutagenic to germ cells (dominant lethal test in male mice). Fludarabine phosphate was not mutagenic to bacteria (Ames test) or mammalian cells either in the presence or absence of metabolic activation.

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.

Use In Specific Populations

Pregnancy

"Pregnancy Category D. See WARNINGS AND PRECAUTIONS section." Based on its mechanism of action, Oforta™ (fludarabine phosphate tablets) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of fludarabine phosphate in pregnant women. Fludarabine phosphate was embryolethal and teratogenic in both rats and rabbits. If Oforta™ (fludarabine phosphate tablets) 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 should be advised to avoid becoming pregnant. Women of childbearing potential and fertile males must take contraceptive measures during and at least for 6 months after the cessation of therapy.

In rats, repeated intravenous doses of fludarabine phosphate at 1.5 times and 4.5 times the recommended human oral dose (40 mg/m2) administered during

organogenesis caused an increase in resorptions, skeletal and visceral malformations (cleft palate, exencephaly, and fetal vertebrae deformities) and decreased fetal body weights. Maternal toxicity was not apparent at 1.5 times the human oral dose, and was limited to slight body weight decreases at 4.5 times the human oral dose. In rabbits, repeated intravenous doses of fludarabine phosphate at 2.4 times the human oral dose administered during organogenesis increased embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses. A significant increase in malformations including cleft palate, hydrocephaly, adactyly, brachydactyly, fusions of the digits, diaphragmatic hernia, heart/great vessel defects, and vertebrae/rib anomalies were seen in all dose levels ( ≥ 0.3 times the human oral dose).

Nursing Mothers

It is not known whether Oforta™ (fludarabine phosphate tablets) is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions including tumorigenicity in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of 78 previously treated patients with B-CLL treated with Oforta™ (fludarabine phosphate tablets) 50% were ≥ age 65 and 3% were ≥ age 75. The response rate was generally lower among patients age 65 and older. Among previously treated patients (Study 1) age 65 and older, the overall objective response, according to standardized response criteria developed by the National Cancer Institute CLL Working Group (NCI criteria), was 41%. The safety profile among younger and older patients on study was similar. Other reported clinical experience has not identified differences in responses or safety between older and younger patients.

Patients with Renal Impairment

In patients receiving intravenous fludarabine phosphate, the total body clearance of the metabolite 2-fluoro-ara-adenine (2F-ara-A) correlated with the creatinine clearance, indicating the importance of the renal excretion pathway for the elimination of the drug. Renal clearance represented approximately 40% of the total body clearance. Patients with mild to moderate renal impairment (30 to 70 mL/min/1.73 m2) receiving 20% reduced fludarabine phosphate dose had a similar exposure compared to patients with normal renal function receiving the recommended dose (AUC; 21 nM»h/mL versus 20 nM»h/mL). Two patients with severe renal impairment ( < 30 mL/min/1.73 m ) receiving 40% reduced fludarabine phosphate dose had a 40% increase in exposure compared to patients with normal renal function receiving the recommended dose. The mean total body clearance was 172 mL/min for patients with normal renal function, 124 mL/min for patients with mild to moderately impaired renal function, and 71 mL/min for the two patients with severe renal impairment.


This monograph has been modified to include the generic and brand name in many instances.

 

OverDose

High doses of fludarabine phosphate [See INDICATIONS AND USAGE and WARNINGS AND PRECAUTIONS] 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 overdosage. Treatment consists of drug discontinuation and supportive therapy. In Study 2, two patients ingested an overdose of 20% to 33% of Oforta™ (fludarabine phosphate tablets) . No serious side effects were reported.

ContrainDications

None


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

Fludarabine phosphate (2F-ara-AMP) is a synthetic purine nucleotide antimetabolite agent. Upon administration, 2F-ara-AMP is rapidly dephosphorylated in the plasma to 2F-ara-A, which then enters into the cell. Intracellularly, 2F-ara-A is converted to the 5'-triphosphate, 2-fluoro-ara-ATP (2F-ara-ATP). 2F-ara-ATP competes with deoxyadenosine triphosphate for incorporation into DNA. Once incorporated into DNA, 2F-ara-ATP functions as a DNA chain terminator, inhibits DNA polymerase alpha, gamma, and delta, and inhibits ribonucleoside diphosphate reductase. 2F-ara-A also inhibits DNA primase and DNA ligase I. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.

Pharmacodynamics

Cardiac Electrophysiology

In a randomized, uncontrolled, open-label, parallel study, patients with B-cell CLL were administered a single dose of Oforta™ 40 mg/m2 (n = 42) or intravenous fludarabine phosphate 25 mg/m (n=14). The maximum increase in the baseline-corrected mean change in QTcI (individual-corrected QT interval) following treatment with Oforta™ (fludarabine phosphate tablets) was less than 10 milliseconds.

Pharmacokinetics

Studies with the intravenous product have demonstrated that fludarabine phosphate is converted to the active metabolite, 2F-ara-A. Clinical pharmacology studies have focused on 2F-ara-A pharmacokinetics.

Following administration of the intravenous product, systemic plasma clearance of 2F-ara-A is approximately 117 mL/min to 145 mL/min. After five daily 30 minute intravenous infusions of 25 mg 2F-ara- AMP/m2 to cancer patients, trough concentrations of 2F-ara-A increased by a factor of about 2. The terminal half-life of 2F-ara-A was approximately 20 hours. Plasma protein binding of 2F-ara-A was approximately 19% to 29%. A correlation was noted between the degree of absolute granulocyte count nadir and increased area under the concentration x time curve (AUC).

2F-ara-A exhibits dose proportional increases in AUC and Cmax after single oral doses of 50 mg, 70 mg or 90 mg of 2F-ara-AMP. Cmax of 2F-ara-A occurs 1 hour to 2 hours after single or multiple oral doses and is approximately 20 % to 30 % of the maximum plasma concentrations produced at the end of a 30 minute intravenous infusion of the same dose. The absolute oral bioavailability of 2F-ara-A is 50 - 65% following single and repeated doses of Oforta™ (fludarabine phosphate tablets) . Similar systemic exposure (AUC) was observed after a single 40 mg/m Oforta™ and a single 25 mg/m2 fludarabine phosphate intravenous dose. The terminal half-life of 2F-ara-A was similar to that following intravenous administration; approximately 20 hours. The Cmax, AUC and terminal half-life of 2F-ara-A are unaffected when administered with a high fat meal, although Tmax is slightly delayed from 1.3 hours to 2.2 hours.

Following intravenous administration, renal clearance of 2F-ara-A represents approximately 40% of the total body clearance of fludarabine phosphate, and total body clearance is inversely correlated with serum creatinine and creatinine clearance. In two patients with median creatinine clearance of 22 mL/min/1.73 m2, 2F-ara-A clearance was reduced by 56%. Dosage adjustment based on creatinine clearance is recommended as follows:

Reduce dose by 20% in patients with mild to moderate renal impairment (creatinine clearance 30 to 70 mL/min/1.73 m2). [See WARNINGS AND PRECAUTIONS]

Reduce dose by 50% in patients with severe renal impairment (creatinine clearance < 30 mL/min/1.73 m2). [See WARNINGS AND PRECAUTIONS]

Clinical Studies

Study 1, a single-arm, open-label study of Oforta™ (fludarabine phosphate tablets) was conducted in 78 adult patients with CLL refractory to at least one prior standard alkylating-agent containing regimen. In this multicenter study patients were treated with Oforta™ (fludarabine phosphate tablets) at a dose of 40 mg/m daily for 5 days every 28 days. The patient population median age was 64.5 years and consisted of 72% males and 28% females. Ninety-nine percent of the patients were Caucasian. The Rai stage for patients entering the study was: Stage 0 (3.9%), Stage I (20.5%), Stage II (32.1%), Stage III (11.5%), and Stage IV (32.1%). The mean number of treatment cycles was 5.1 with a mean daily dose of Oforta™ (fludarabine phosphate tablets) of 38 mg/m2. The overall objective response, according to standardized response criteria developed by the National Cancer Institute CLL Working Group (NCI criteria), was 51%, including 18% complete responses and 33% partial responses. The overall response rate, according to standardized criteria developed by the International Workshop on CLL (IWCLL criteria), was 46%, including 21% complete responses and 26% partial responses. Data on duration of response was not collected.

In Study 2, a supportive single-arm, open-label study, Oforta™ (fludarabine phosphate tablets) was administered to 81 previously untreated patients with B-CLL. In this multicenter study each patient was treated with Oforta™ (fludarabine phosphate tablets) at a dose of 40 mg/m2 daily for 5 days every 28 days. The patient population median age was 64.0 years and consisted of 63% males and 37% females. Ninety-nine percent of the patients were Caucasian. The Rai stage for patients entering the study was: Stage 0 (3.7%), Stage I (37.0%), Stage II (37.0%), Stage III (9.9%), and Stage IV (12.3%). The mean number of treatment cycles was 5.9 with a mean daily dose per patient of 71 mg to 74 mg. The overall responses rate, according to NCI criteria, was 80%, including 12% complete responses and 68% partial responses. The overall response rate, according to IWCLL criteria, was 72%, including 37% complete responses and 35% partial responses. The median duration of response was 22.9 months.

Study 3 was a supportive randomized controlled open label study in patients with previously untreated B-CLL that included fludarabine phosphate monotherapy and fludarabine phosphate combination therapy arms. In this study 107 evaluable patients received Oforta™ (fludarabine phosphate tablets) 40mg/m orally daily for 5 days every 28 days. The overall response rate according to modified NCI criteria was 74% and the CR plus nodular PR rate was 41%.

REFERENCES

1. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH Alert 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2 .html

3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.

4. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd. ed.) Pittsburgh, PA: Oncology Nursing Society.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

OFORTA
(oh-FORT-tuh)
(oral fludarabine phosphate) Tablets

Read this Patient Information leaflet before you start taking OFORTA™ (fludarabine phosphate tablets) and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What Is OFORTA™?

OFORTA™(oral fludarabine phosphate tablets) is a prescription anticancer medicine that slows or stops the growth of cancer cells in adults with chronic lymphocytic leukemia (CLL). OFORTA™ (fludarabine phosphate tablets) also stops or slows the growth of some healthy cells. This can cause side effects that you should know about and report to your healthcare provider.

OFORTA™ (fludarabine phosphate tablets) has not been studied in children.

What is the most important information I should know about OFORTA™ (fludarabine phosphate tablets) ?

On rare occasions people taking OFORTA™ (fludarabine phosphate tablets) can have life-threatening symptoms. If you:

  • have problems seeing
  • feel very sleepy, tired, or confused
  • have shortness of breath or have trouble breathing
  • have yellow skin or dark urine

Tell your healthcare provider right away. What should I tell my healthcare provider before taking OFORTA™ (fludarabine phosphate tablets) ?

Before taking OFORTA™ (fludarabine phosphate tablets) , tell your healthcare provider about all of your medical conditions, including if you:

  • have kidney problems
  • have bleeding problems
  • are pregnant or plan to become pregnant. It is not known if OFORTA™ (fludarabine phosphate tablets) will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant. Women should not get pregnant during treatment with OFORTA™ (fludarabine phosphate tablets) because the unborn baby may be harmed. Both men and women must take contraceptive measures during and for at least six months after cessation of therapy. Call your doctor right away if you become pregnant during or in the six months after treatment with OFORTA™ (fludarabine phosphate tablets) .
  • are breast- feeding or plan to breast-feed. It is not known if OFORTA™ (fludarabine phosphate tablets) passes into your breast milk. You and your healthcare provider should decide if you will take OFORTA™ (fludarabine phosphate tablets) or breast-feed. You should not do both.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Using OFORTA™ (fludarabine phosphate tablets) with certain other medicines may affect each other. Using OFORTA™ (fludarabine phosphate tablets) with other medicines may cause serious side effects.

Know the medicines you take. Keep a list of them with you to show your healthcare provider.

How should I take OFORTA™ (fludarabine phosphate tablets) ?

  • Take OFORTA™ (fludarabine phosphate tablets) exactly as your healthcare provider tells you to take it.
  • Your healthcare provider will tell you how much and when to take OFORTA™ (fludarabine phosphate tablets) .
  • OFORTA™ (fludarabine phosphate tablets) can be taken with or without food.
  • Push tablets through foil to open. Do not remove tablets from individual blisters until immediately prior to taking or administering each scheduled dose.
  • OFORTA™ (fludarabine phosphate tablets) tablets have to be swallowed whole with water; they should never be chewed, crushed, or broken. If you cannot swallow OFORTA™ (fludarabine phosphate tablets) whole, ask your healthcare provider if you can take another form of fludarabine.
  • If you miss a dose call your healthcare provider.
  • If you take too much call your healthcare provider.

What should I avoid while taking OFORTA™ (fludarabine phosphate tablets) ?

  • Do not allow other people or pets to touch or take OFORTA™ (fludarabine phosphate tablets) .
  • Avoid letting the tablets (whole or broken) touch your skin
  • Do not chew tablets or hold them in your mouth. Swallow tablets right away.
  • Do not breathe in any powder or residue from a broken tablet.
  • If you touch a broken tablet, wash the area thoroughly with soap and water.
  • If any OFORTA™ (fludarabine phosphate tablets) gets in your eyes, wash your eyes right away with water for at least 15 minutes, and call your healthcare provider right away.
  • Call your healthcare provider right away in case of a skin reaction.

What are the possible side effects of OFORTA™ (fludarabine phosphate tablets) ?

See "What is the most important information I should know about OFORTA™ (fludarabine phosphate tablets) ?"

OFORTA™ (fludarabine phosphate tablets) may cause serious side effects, including:

Low blood cell counts.

OFORTA™ (fludarabine phosphate tablets) lessens the number of blood cells that fight infection, help your blood to clot, and carry oxygen throughout your body. This can result in

  • Infection
  • Bleeding
  • Tiredness

Avoid activities that can raise your chances of these conditions. Your healthcare provider will check your blood counts so that you will know when you are most at risk for infection, bleeding, and tiredness.

Call your healthcare provider right away if you have a temperature of 100.5 F. or above or do not feel well. Do not take a fever medicine until you check with your healthcare provider.

OFORTA™ (fludarabine phosphate tablets) may cause other side effects, including:

  • nausea and vomiting
  • loss of appetite
  • skin rash
  • swelling in your legs
  • diarrhea
  • redness and irritation inside your mouth (stomatitis)
  • abdominal and muscle pain.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of OFORTA™ (fludarabine phosphate tablets) . For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How should I store and throw away OFORTA™ (fludarabine phosphate tablets) ?

  • Store OFORTA™ (fludarabine phosphate tablets) at 59-86°F (15-30°C).
  • Keep under normal light in a child-resistant container.
  • Safely throw away medicine that is out of date or no longer needed.
  • Do not put OFORTA™ (fludarabine phosphate tablets) in your regular household trash.
  • Ask your healthcare provider or pharmacist for directions about how to safely throw away and handle OFORTA™ (fludarabine phosphate tablets) .

Keep OFORTA™ (fludarabine phosphate tablets) and all medicines out of the reach of children.

General information about OFORTA™ (fludarabine phosphate tablets)

Medicines are sometimes prescribed for conditions that are not mentioned in patient information. Do not use OFORTA™ (fludarabine phosphate tablets) for a condition for which it was not prescribed. Do not give OFORTA™ (fludarabine phosphate tablets) to other people, even if they have the same symptoms you have. It may harm them.

This patient information leaflet summarizes the most important information about OFORTA™ (fludarabine phosphate tablets) . For more information about OFORTA™ (fludarabine phosphate tablets) , talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about OFORTA™ (fludarabine phosphate tablets) that is written for health professionals. For more information call 1-800-633-1610.

What are the ingredients in OFORTA™?

Active ingredients: fludarabine phosphate

Inactive ingredients: microcrystalline cellulose, lactose monohydrate, colloidal anhydrous silicon dioxide, croscarmellose sodium and magnesium stearate. The film-coat contains hypromellose, talc, titanium dioxide (E171) and ferric oxide pigment (red/E172, yellow/E172).


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

FLUDARABINE - ORAL

 

(flew-DARE-uh-bean)

 

WARNING: This medication may cause certain severe blood and bone marrow problems (low red blood cells/white blood cells/platelets, hemolytic anemia). These problems can decrease your body's ability to prevent/stop bleeding, fight infection, or carry enough oxygen in your blood. Tell your doctor immediately if you develop easy bleeding/bruising, unusual tiredness, fast/pounding heartbeat, yellowing eyes/skin, red/brown urine, pale/bluish skin, or signs of infection (e.g., fever, chills, persistent sore throat).

Fludarabine may rarely cause severe (sometimes fatal) central nervous system problems. Symptoms may not occur until weeks after your last treatment. Tell your doctor immediately if you notice any vision changes, seizures, agitation, confusion, or numbness/tingling.

Do not use fludarabine with pentostatin (deoxycoformycin). Use of these 2 medications together has caused fatal lung problems.

 

USES: This medication is used to treat leukemia. It works by slowing or stopping the growth of cancer cells.

 

HOW TO USE: This medicine comes with a Patient Information Leaflet. Read it carefully. Ask your doctor, nurse, or pharmacist any questions that you may have about this medicine.

Take this medication by mouth with or without food, usually once a day for 5 days in a row or as directed by your doctor. This 5-day cycle may be repeated after 28 days, usually for up to 6 cycles. Swallow the tablet(s) whole with a glass of water. Do not break, crush, or chew the tablets.

Dosage is based on your medical condition, body size, and response to treatment. Your doctor will check your blood counts to make sure you can receive your next cycle. Keep all medical/lab appointments.

Do not increase your dose or take this medication more often than prescribed. Your condition will not improve any faster, and the risk of serious side effects may be increased.

Since this drug can be absorbed through the skin and lungs, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

 

 

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning section.

Nausea, vomiting, diarrhea, tiredness, and loss of appetite may occur. Nausea and vomiting can be severe. In some cases, your doctor may prescribe medication to prevent or relieve nausea and vomiting. Eating several small meals, not eating before treatment, or limiting activity may help lessen some of these effects. If these effects persist or worsen, tell your doctor or pharmacist promptly.

Many people using this medication may have serious side effects. However, your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. To lower your risk of serious side effects, your doctor will follow your condition closely and order lab tests.

Pain or sores in the mouth and throat may occur. Brush your teeth gently/carefully, avoid using mouthwash that contains alcohol, and rinse your mouth frequently with cool water mixed with baking soda or salt. It may also be best to eat soft, moist foods.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fast/irregular heartbeat, swelling ankles/feet.

This medication affects your blood cells, reducing your ability to fight infections. Although fever and chills are common side effects of fludarabine, they may also be signs of an infection. Tell your doctor if you develop chills or fever.

Fludarabine sometimes causes side effects due to the rapid destruction of cancer cells (tumor lysis syndrome). To lower your risk, drink plenty of fluids unless your doctor directs you otherwise. Also, your doctor may prescribe an additional medication. Tell your doctor right away if you have symptoms such as: low back/side pain (flank pain), pink/bloody urine, change in the amount of urine, painful urination, muscle spasms/weakness.

Seek immediate medical attention if any of these rare but very serious side effects occur: bloody/black/tarry stool, persistent cough, coughing up blood, painful/difficult breathing, chest pain, seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Oforta (fludarabine phosphate tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before using fludarabine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: hemolytic anemia, severe kidney disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: current infections, certain infections (opportunistic infections such as fungal infections), certain virus conditions (herpes, chickenpox), blood disorders (e.g., anemia, clotting problems), immune system problems, kidney problems, liver disease, skin cancer.

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.

Wash your hands well to prevent the spread of infections. Avoid contact with people who have illnesses that may spread to others (e.g., flu, chickenpox).

To lower your chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Before having surgery, tell your doctor or dentist that you are taking this medication. Before receiving any blood transfusions, tell your doctor that you are taking/have taken fludarabine.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects (e.g., infection, bleeding) while using this drug.

This drug is not recommended for use during pregnancy. It may harm the unborn baby. If you become pregnant or think you may be pregnant, tell your doctor immediately. To avoid pregnancy, both males and females using this drug should use reliable form(s) of birth control (e.g., birth control pills, condoms) during treatment and for 6 months after treatment has ended. Consult your doctor for details and to discuss effective forms of birth control.

It is not known whether this medication passes into breast milk. However, it may have undesirable effects on a nursing infant. Therefore, breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: live vaccines (e.g., flu vaccine inhaled through the nose, typhoid/polio vaccine taken by mouth), pentostatin, other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab).

If you are currently using any of these medications listed above or planning any vaccinations, tell your doctor or pharmacist before starting fludarabine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin, enoxaparin), dipyridamole, salicylates/NSAIDs (e.g., aspirin, ibuprofen, naproxen).

Check all prescription and nonprescription medicine labels carefully since many contain pain relievers/fever reducers (NSAIDs such as ibuprofen, naproxen, and aspirin) that can increase your risk of bleeding. Low-dose aspirin should be continued if prescribed by your doctor for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day). Consult your doctor or pharmacist for more details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood count, kidney function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store medication in the original package at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not open protective package until ready to use. Do not freeze. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised March 2014. Copyright(c) 2014 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Oforta

Generic Name: fludarabine (oral) (Pronunciation: floo DAR a been)

  • What is fludarabine (Oforta)?
  • What are the possible side effects of fludarabine (Oforta)?
  • What is the most important information I should know about fludarabine (Oforta)?
  • What should I discuss with my healthcare provider before I take fludarabine (Oforta)?
  • How should I take fludarabine (Oforta)?
  • What happens if I miss a dose (Oforta)?
  • What happens if I overdose (Oforta)?
  • What should I avoid while taking fludarabine (Oforta)?
  • What other drugs will affect fludarabine (Oforta)?
  • Where can I get more information?

What is fludarabine (Oforta)?

Fludarabine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Fludarabine is used to treat B-cell chronic lymphocytic leukemia (CLL).

Fludarabine is usually given after other cancer medications have been tried without successful response to treatment.

Fludarabine may also be used for other purposes not listed in this medication guide.

What are the possible side effects of fludarabine (Oforta)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pale or yellowed skin, dark colored urine;
  • fast or slow heart rate, weak pulse, trouble concentrating, feeling tired or short of breath;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat, nausea, vomiting, loss of appetite;
  • vision problems, confusion, agitation, changes in behavior, or feeling like you might pass out;
  • cough with yellow or green mucus, stabbing chest pain, trouble breathing;
  • black or bloody stools, coughing up blood;
  • lower back pain, blood in your urine, pain or burning when you urinate;
  • urinating less than usual or not at all;
  • numbness or tingly feeling around your mouth; or
  • muscle weakness, tightness, or contraction, overactive reflexes.

Less serious side effects may include:

  • muscle pain;
  • swelling in your legs;
  • mild nausea, diarrhea, stomach pain;
  • cold symptoms such as runny or stuffy nose, sneezing;
  • sweating; or
  • mild itching or skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Oforta (fludarabine phosphate tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about fludarabine (Oforta)?

Do not use fludarabine if you are pregnant. It could harm the unborn baby. Use birth control to prevent pregnancy while you are taking fludarabine, whether you are a man or a woman. Keep using birth control for at least 6 months after your treatment ends. Fludarabine use by either parent may cause birth defects.

Before you take fludarabine, tell your doctor if you have kidney disease, bone marrow problems, or a weak immune system.

If you need to have a blood transfusion, tell your caregivers ahead of time that you are being treated with fludarabine.

Fludarabine can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection. Your blood may need to be tested often. Visit your doctor regularly.

Contact your doctor at once if you develop signs of infection such as fever, cough, sore throat, flu symptoms, easy bruising or bleeding (nosebleeds, bleeding gums), loss of appetite, nausea and vomiting, mouth sores, or unusual weakness.

Side Effects Centers
  • Oforta
  • « Previous

Patient Detailed How Take

What should I discuss with my healthcare provider before I take fludarabine (Oforta)?

You should not use this medication if you are allergic to fludarabine, or if you are also being treated with a cancer medicine called pentostatin (Nipent).

If you have any of these other conditions, you may need a fludarabine dose adjustment or special tests:

  • kidney disease;
  • bone marrow problems; or
  • a weak immune system.

FDA pregnancy category D. Do not use fludarabine if you are pregnant. It could harm the unborn baby.

Use birth control to prevent pregnancy while you are taking fludarabine, whether you are a man or a woman. Keep using birth control for at least 6 months after your treatment ends. Fludarabine use by either parent may cause birth defects.

It is not known whether fludarabine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking fludarabine.

How should I take fludarabine (Oforta)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Fludarabine is usually taken daily for 5 days in a row every 28 days. Once your body has responded well to the medication, your doctor may recommend additional treatment cycles.

Fludarabine may be taken with or without food.

Do not crush, chew, or break a fludarabine tablet.

Swallow the tablet whole with water.

Do not use a tablet that has been accidentally broken. The powder from a crushed or broken pill can be dangerous if you breathe it in, or if it gets in your eyes, mouth, or nose, or on your skin. Ask your doctor or pharmacist how to safely handle and dispose of a broken tablet.

If you accidentally touch a broken tablet, wash your skin with soap and water. Call your doctor if you develop a skin rash or severe irritation.

If the powder from a broken tablet gets in your eyes, rinse them with water for at least 15 minutes.

Fludarabine can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill.

Contact your doctor at once if you develop signs of infection such as fever, cough, sore throat, flu symptoms, easy bruising or bleeding (nosebleeds, bleeding gums), loss of appetite, nausea and vomiting, mouth sores, or unusual weakness.

Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests. Visit your doctor regularly.

If you need to have a blood transfusion, tell your caregivers ahead of time that you are taking fludarabine.

Keep each tablet in its blister pack until you are ready to take it. Push a tablet through the foil when you are ready to take the medicine.

Do not allow other people to handle a fludarabine tablet. Keep the medicine in a place where children and pets cannot get to it.

Store at room temperature away from moisture and heat.

Do not throw away unused or expired fludarabine tablets in your household trash. Ask your pharmacist where to locate a community pharmaceutical take back disposal program.

Side Effects Centers
  • Oforta

Patient Detailed Avoid Taking

What happens if I miss a dose (Oforta)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Oforta)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include fever, chills, flu symptoms, mouth sores, easy bruising or bleeding, purple or red spots under your skin, behavior changes, and vision loss.

What should I avoid while taking fludarabine (Oforta)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid activities that increase your risk of bleeding or injury. Brush your teeth gently and use extra care while shaving.

If you have a fever, avoid taking any fever medication without first asking your doctor.

What other drugs will affect fludarabine (Oforta)?

There may be other drugs that can interact with fludarabine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about fludarabine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.03. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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