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HIGHLIGHTS OF PRESCRIBING INFORMATION |
These highlights do not include all the information needed to use Oforta™ safely and effectively. See full prescribing information for Oforta™.
Oforta™ (fludarabine phosphate tablets) for Oral Use.
Initial U.S. Approval: 1991
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WARNING: CNS TOXICITY, HEMOLYTIC ANEMIA, AND PULMONARY TOXICITY
See full prescribing information for complete boxed warning.
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Severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m2/day for 5 days to 7 days) than the recommended intravenous dose. This toxicity was seen in ≤0.2% of patients treated at the recommended intravenous dose levels (25 mg/m2). (5.1)
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Life-threatening and sometimes fatal autoimmune hemolytic anemia has been reported after one or more cycles of treatment. (5.2)
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High incidence of fatal pulmonary toxicity was observed in a clinical investigation of the combination of fludarabine phosphate with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL). (5.3)
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INDICATIONS AND USAGE
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Oforta™ (fludarabine phosphate tablets) is a nucleotide metabolic inhibitor 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. A direct comparison of the clinical efficacy and safety of orally administered Oforta™ relative to intravenously administered fludarabine phosphate has not been studied.
(1)
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DOSAGE AND ADMINISTRATION
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Note: The oral dose of Oforta™ is different than the intravenous fludarabine phosphate dose.
Chronic Lymphocytic Leukemia (CLL) (2.1):
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The recommended adult dose is 40 mg/m2 administered daily for five consecutive days by the oral route.
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Begin each 5-day course of treatment every 28 days.
Renal Impairment (2.2):
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Reduce dose by 20% in patients with mild to moderate renal impairment (creatinine clearance 30 to 70 mL/min/1.73 m2).
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Reduce dose by 50% in patients with severe renal impairment (creatinine clearance < 30 mL/min/1.73 m2)
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DOSAGE FORMS AND STRENGTHS
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10 milligram tablets. (see 3)
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CONTRAINDICATIONS
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WARNINGS AND PRECAUTIONS
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Severe bone marrow suppression, notably anemia, thrombocytopenia and neutropenia. Monitor blood counts before and during treatment. (5.2)
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Infections. Monitor for signs or symptoms of infection. (5.3)
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Tumor lysis syndrome. Take precautions for patients at high risk. (5.4)
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Transfusion-associated graft-versus-host disease. Use only irradiated blood products for transfusions. (5.6)
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Oforta™ dose should be adjusted in patients with mild to moderate (creatinine clearance 30 to 70 mL/min/1.73 m2) or severe (creatinine clearance < 30 mL/min/1.73 m2) renal impairment. (5.7)
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Fetal harm may occur when administered to a pregnant woman. Women of childbearing potential and fertile males must take contraceptive measures during and at least for 6 months after the cessation of therapy. (5.9)
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ADVERSE REACTIONS
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Most common adverse reactions (incidence > 30%) include myelosuppression (neutropenia, thrombocytopenia and anemia). Fever, weakness, infection, pain, cough and anorexia were also reported as common adverse reactions. (6)
To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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DRUG INTERACTIONS
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Oforta™ in combination with pentostatin is not recommended due to the risk of severe pulmonary toxicity. (5.3 and 7.1)
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See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling |
Revised: 07/2009 |
Back to Highlights and Tabs
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FULL PRESCRIBING INFORMATION: CONTENTS* |
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WARNING: CNS TOXICITY, HEMOLYTIC ANEMIA, AND PULMONARY TOXICITY
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Chronic Lymphocytic Leukemia (CLL)
2.2 Renal Impairment
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Neurotoxicity
5.2 Bone Marrow Suppression
5.3 Pulmonary Toxicity
5.4 Infections
5.5 Tumor Lysis Syndrome
5.6 Use of Transfusions
5.7 Renal Impairment
5.8 Monitoring
5.9 Pregnancy
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Post Marketing Experience
7 DRUG INTERACTIONS
7.1 Pentostatin
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Patients with Renal Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Bone Marrow Suppression
17.2 Infections
17.3 Pregnancy
17.4 Handling and Disposal
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FULL PRESCRIBING INFORMATION
WARNING: CNS TOXICITY, HEMOLYTIC ANEMIA, AND PULMONARY TOXICITY
Severe neurologic effects, including blindness, coma, and death were observed in dose-ranging studies in patients with acute leukemia when fludarabine phosphate was administered at high doses. This severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m2/day for 5 days to 7 days) than the recommended intravenous dose (25 mg/m2/day). 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. [See Warnings and Precautions (5.1)] Periodic neurological assessments are recommended.
Instances of life-threatening and sometimes fatal autoimmune hemolytic anemia have been reported after one or more cycles of treatment with fludarabine phosphate. Patients undergoing treatment with Oforta™ should be eva luated and closely monitored for hemolysis. [See Warnings and Precautions (5.2)]
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). Therefore, the use of Oforta™ in combination with pentostatin is not recommended [See Warnings and Precautions (5.3)]
1 INDICATIONS AND USAGE
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.
2 DOSAGE AND ADMINISTRATION
2.1 Chronic Lymphocytic Leukemia (CLL)
The oral dose of Oforta™ is different than the intravenous fludarabine phosphate dose.
The recommended adult dose of Oforta™ is 40 mg/m2 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™ 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™ to be administered based on body surface area (BSA):
TABLE 1: SUGGESTED NUMBER OF TABLETS TO BE ADMINISTERED
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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 |
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0.75 – 0.88 |
30 mg |
3 |
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0.89 – 1.13 |
40 mg |
4 |
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1.14 – 1.38 |
50 mg |
5 |
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1.39 – 1.63 |
60 mg |
6 |
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| 以下是“全球医药”详细资料 |
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