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Avopef

ETOPOSIDE

Standard Dose

2 DOSAGE AND ADMINISTRATION Refractory Testicular Cancer : 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5. ( 2.2 ) Small Cell Lung Cancer : 35 mg/m 2 administered intravenously daily on days 1 to 4, or 50 mg/m 2 administered intravenously daily on days 1 to 5. ( 2.3 ) Dilute AVOPEF prior to intravenous infusion over 30- to 60-minutes. ( 2.5 ) 2.1 Important Dosage and Administration Information Dilute AVOPEF to a final concentration of 0.2 to 0.4 mg/mL prior to administration [see Dosage and Administration (2.5) ]. Administer diluted AVOPEF by intravenous infusion over 30 to 60 minutes to reduce the risk of infusion-related reactions including hypotension [see Dosage and Administration (2.5) ]. Before each AVOPEF administration and at appropriate intervals during and after therapy, monitor complete blood counts with differential and serum albumin [see Warnings and Precautions (5.1, 5.5) ]. If severe reactions occur, reduce the dosage or discontinue AVOPEF and take appropriate corrective measures according to the clinical judgment of the healthcare provider. 2.2 Recommended Dosage for Refractory Testicular Cancer The recommended dosage of AVOPEF is: 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5 Repeat treatment cycles every 3 to 4 weeks. 2.3 Recommended Dosage for Small Cell Lung Cancer The recommended dosage of AVOPEF is: 35 mg/m 2 administered intravenously daily on Days 1 to 4, or 50 mg/m 2 administered intravenously daily on Days 1 to 5 Repeat treatment cycles every 3 to 4 weeks. 2.4 Recommended Dosage in Patients with Renal Impairment No dosage modification is recommended for patients with creatinine clearance (CLcr) > 50 mL/min. The recommended dosage of AVOPEF in patients with CLcr of 15 to 50 mL/min is listed in Table 1. Table 1: Recommended Dosage of AVOPEF in Patients with Creatine Clearance of 15 to 50 mL/min *Repeat treatment cycles every 3 to 4 weeks. Recommended AVOPEF Dosage * Refractory Testicular Cancer 37 mg/m 2 to 75 mg/m 2 Days 1 through 5 75 mg/m 2 Days 1, 3 and 5 Small Cell Lung Cancer 26 mg/m 2 Days 1 through 4 37 mg/m 2 Days 1 through 5 A recommended dosage of AVOPEF has not been established for patients with creatinine clearance < 15 mL/min. 2.5 Preparation for Intravenous Administration Preparation AVOPEF is a hazardous drug. Follow applicable special handling and disposal procedures. [see References (15) ]. Dilute AVOPEF with either 5% Dextrose Injection, USP, or 0.9% Sodium Chloride Injection, USP, to a final concentration of 0.2 to 0.4 mg/mL. If solutions of AVOPEF are prepared at concentrations above 0.4 mg/mL, precipitation may occur. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Administration Do not administer AVOPEF by rapid intravenous injection. To reduce the risk of infusion-related reactions including hypotension, administer diluted AVOPEF intravenously over 30 to 60 minutes. A longer duration of administration may be used if there is a large volume of fluid to be infused. Storage AVOPEF, diluted to a concentration of 0.2 mg/mL is stable for 96 hours or diluted to a concentration of 0.4 mg/mL is stable for 24 hours at room temperature (25°C) under normal room fluorescent light in polyvinyl chloride (PVC) container. After first use, store the partially used multiple-dose vial in the original carton at controlled room temperature, 20°C to 25° C (68°F to 77° F) for up to 28 days. Discard unused portion of the multiple-dose vial after 28 days.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE AVOPEF is a topoisomerase inhibitor indicated, in combination with other chemotherapy and/or immunotherapy, for the treatment of adult patients with: Refractory testicular cancer ( 1.1 ) Small cell lung cancer ( 1.2 ) 1.1 Refractory Testicular Cancer AVOPEF, in combination with chemotherapy, is indicated for the treatment of refractory testicular cancer in adult patients.

Summary

Dosage and administration 2 DOSAGE AND ADMINISTRATION Refractory Testicular Cancer : 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5. ( 2.2 ) Small Cell Lung Cancer : 35 mg/m 2 administered intravenously daily on days 1 to 4, or 50 mg/m 2 administered intravenously daily on days 1 to 5. ( 2.3 ) Dilute AVOPEF prior to intravenous infusion over 30- to 60-minutes. ( 2.5 ) 2.1 Important Dosage and Administration Information Dilute AVOPEF to a final concentration of 0.2 to 0.4 mg/mL prior to administration [see Dosage and Administration (2.5) ].

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE AVOPEF is a topoisomerase inhibitor indicated, in combination with other chemotherapy and/or immunotherapy, for the treatment of adult patients with: Refractory testicular cancer ( 1.1 ) Small cell lung cancer ( 1.2 ) 1.1 Refractory Testicular Cancer AVOPEF, in combination with chemotherapy, is indicated for the treatment of refractory testicular cancer in adult patients. 1.2 Small Cell Lung Cancer AVOPEF, in combination with chemotherapy and immunotherapy, is indicated for the first-line treatment of small cell lung cancer (SCLC) in adult patients. Dosage and administration 2 DOSAGE AND ADMINISTRATION Refractory Testicular Cancer : 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5. ( 2.2 ) Small Cell Lung Cancer : 35 mg/m 2 administered intravenously daily on days 1 to 4, or 50 mg/m 2 administered intravenously daily on days 1 to 5. ( 2.3 ) Dilute AVOPEF prior to intravenous infusion over 30- to 60-minutes. ( 2.5 ) 2.1 Important Dosage and Administration Information Dilute AVOPEF to a final concentration of 0.2 to 0.4 mg/mL prior to administration [see Dosage and Administration (2.5) ]. Administer diluted AVOPEF by intravenous infusion over 30 to 60 minutes to reduce the risk of infusion-related reactions including hypotension [see Dosage and Administration (2.5) ]. Before each AVOPEF administration and at appropriate intervals during and after therapy, monitor complete blood counts with differential and serum albumin [see Warnings and Precautions (5.1, 5.5) ]. If severe reactions occur, reduce the dosage or discontinue AVOPEF and take appropriate corrective measures according to the clinical judgment of the healthcare provider. 2.2 Recommended Dosage for Refractory Testicular Cancer The recommended dosage of AVOPEF is: 50 mg/m 2 to 100 mg/m 2 administered intravenously daily on Days 1 to 5, or 100 mg/m 2 administered intravenously daily on Days 1, 3 and 5 Repeat treatment cycles every 3 to 4 weeks. 2.3 Recommended Dosage for Small Cell Lung Cancer The recommended dosage of AVOPEF is: 35 mg/m 2 administered intravenously daily on Days 1 to 4, or 50 mg/m 2 administered intravenously daily on Days 1 to 5 Repeat treatment cycles every 3 to 4 weeks. 2.4 Recommended Dosage in Patients with Renal Impairment No dosage modification is recommended for patients with creatinine clearance (CLcr) > 50 mL/min. The recommended dosage of AVOPEF in patients with CLcr of 15 to 50 mL/min is listed in Table 1. Table 1: Recommended Dosage of AVOPEF in Patients with Creatine Clearance of 15 to 50 mL/min *Repeat treatment cycles every 3 to 4 weeks. Recommended AVOPEF Dosage * Refractory Testicular Cancer 37 mg/m 2 to 75 mg/m 2 Days 1 through 5 75 mg/m 2 Days 1, 3 and 5 Small Cell Lung Cancer 26 mg/m 2 Days 1 through 4 37 mg/m 2 Days 1 through 5 A recommended dosage of AVOPEF has not been established for patients with creatinine clearance < 15 mL/min. 2.5 Preparation for Intravenous Administration Preparation AVOPEF is a hazardous drug. Follow applicable special handling and disposal procedures. [see References (15) ]. Dilute AVOPEF with either 5% Dextrose Injection, USP, or 0.9% Sodium Chloride Injection, USP, to a final concentration of 0.2 to 0.4 mg/mL. If solutions of AVOPEF are prepared at concentrations above 0.4 mg/mL, precipitation may occur. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Administration Do not administer AVOPEF by rapid intravenous injection. To reduce the risk of infusion-related reactions including hypotension, administer diluted AVOPEF intravenously over 30 to 60 minutes. A longer duration of administration may be used if there is a large volume of fluid to be infused. Storage AVOPEF, diluted to a concentration of 0.2 mg/mL is stable for 96 hours or diluted to a concentration of 0.4 mg/mL is stable for 24 hours at room temperature (25°C) under normal room fluorescent light in polyvinyl chloride (PVC) container. After first use, store the partially used multiple-dose vial in the original carton at controlled room temperature, 20°C to 25° C (68°F to 77° F) for up to 28 days. Discard unused portion of the multiple-dose vial after 28 days. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Severe Myelosuppression : Monitor complete blood counts before each AVOPEF administration and at appropriate intervals during and after therapy. Interrupt AVOPEF for absolute neutrophil counts below 500 cells/mm 3 or platelet counts below 50,000 cells/mm 3 . ( 5.1 ) Hypersensitivity and Infusion-Related Reactions : At the first sign of hypersensitivity, stop the infusion and administer volume expanders, corticosteroids, antihistamines, and pressor agents as appropriate. Permanently discontinue AVOPEF in patients who experience a severe hypersensitivity reaction. Hypotension has

Boxed Warning

WARNING: SEVERE MYELOSUPPRESSION AVOPEF can cause severe myelosuppression resulting in infection or bleeding [see Warnings and Precautions (5.1) ] . Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 [see Warnings and Precautions (5.1) ] . Monitor complete blood cell counts, prior to the administration of AVOPEF and before each subsequent cycle, and at appropriate intervals during and after therapy [see Warnings and Precautions (5.1) ] . WARNING: SEVERE MYELOSUPPRESSION See full prescribing information for complete boxed warning . AVOPEF can cause severe myelosuppression resulting in infection or bleeding. ( 5.1 ) Do not administer AVOPEF to patients with absolute neutrophil counts of less than 500 cells/mm 3 or platelets less than 50,000 cells/mm 3 . ( 5.1 ) Monitor complete blood cell counts, prior to the administration of AVOPEF and before each subsequent cycle, and at appropriate intervals during and after therapy. ( 5.1 )

Monitoring

• 5 WARNINGS AND PRECAUTIONS Severe Myelosuppression : Monitor complete blood counts before each AVOPEF administration and at appropriate intervals during and after therapy.
• Interrupt AVOPEF for absolute neutrophil counts below 500 cells/mm 3 or platelet counts below 50,000 cells/mm 3 .
• ( 5.1 ) Hypersensitivity and Infusion-Related Reactions : At the first sign of hypersensitivity, stop the infusion and administer volume expanders, corticosteroids, antihistamines, and pressor agents as appropriate.
• Permanently discontinue AVOPEF in patients who experience a severe hypersensitivity reaction.

Interaction Notes

• 7 DRUG INTERACTIONS CYP3A Inhibitors and CYP3A Inducers : Avoid concomitant use of strong CYP3A inhibitors and strong CYP3A inducers with AVOPEF.
• ( 7.1 ) Vitamin K Antagonists : Monitor INR more frequently and modify the dosage of the vitamin K antagonists as appropriate.
• Co-administration of AVOEPF with warfarin can result in elevated international normalized ratio (INR).
• ( 7.2 ) 7.1 Effect of Other Drugs on AVOPEF CYP3A Inhibitors Avoid concomitant use of strong CYP3A inhibitors.