Axtle Dosage

Recommended Dosage for Non-Squamous NSCLC

• The recommended dose of AXTLE when administered with cisplatin for initial treatment of locally advanced or metastatic non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes administered prior to cisplatin on Day 1 of each 21-day cycle for up to six cycles in the absence of disease progression or unacceptable toxicity.
• The recommended dose of AXTLE for maintenance treatment of non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity after four cycles of platinum-based first-line chemotherapy.
• The recommended dose of AXTLE for treatment of recurrent non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Recommended Dosage for Mesothelioma

• The recommended dose of AXTLE, when administered with cisplatin, in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Renal Impairment

• AXTLE dosing recommendations are provided for patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater. There is no recommended dose for patients whose creatinine clearance is less than 45 mL/min.

Premedication and Concomitant Medications to Mitigate Toxicity

Vitamin Supplementation

• Initiate folic acid 400 mcg to 1000 mcg orally once daily, beginning 7 days before the first dose of AXTLE and continuing until 21 days after the last dose of AXTLE.
• Administer vitamin B12,1 mg intramuscularly, 1 week prior to the first dose of AXTLE and every 3 cycles thereafter. Subsequent vitamin B12injections may be given the same day as treatment with AXTLE. Do not substitute oral vitamin B12for intramuscular vitamin B12.

Corticosteroids

• Administer dexamethasone 4 mg orally twice daily for three consecutive days, beginning the day before each AXTLE administration.

Dosage Modification of Ibuprofen in Patients with Mild to Moderate Renal Impairment Receiving AXTLE

In patients with creatinine clearances between 45 mL/min and 79 mL/min, modify administration of ibuprofen as follows:

• Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of AXTLE.
• Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided.

Dosage Modifications for Adverse Reactions

Obtain complete blood count on Days 1, 8, and 15 of each cycle. Assess creatinine clearance prior to each cycle. Do not administer AXTLE if the creatinine clearance is less than 45 mL/min.

Delay initiation of the next cycle of AXTLE until:

• recovery of non-hematologic toxicity to Grade 0-2,
• absolute neutrophil count (ANC) is 1500 cells/mm3or higher, and
• platelet count is 100,000 cells/mm3or higher.

Upon recovery, modify the dosage of AXTLE in the next cycle as specified in Table 1.

For dosing modifications for cisplatin, refer to the prescribing information.

Preparation for Administration

• AXTLE is a hazardous drug. Follow applicable special handling and disposal procedures.1
• Calculate the dose of AXTLE and determine the number of vials needed.
• Reconstitute AXTLE to achieve a concentration of 25 mg/mL as follows:
• Reconstitute each 100-mg vial with 4.2 mL of 5% Dextrose Injection, USP (preservative-free)
• Reconstitute each 500-mg vial with 20 mL of 5% Dextrose Injection, USP (preservative-free)
• Do not use calcium-containing solutions for reconstitution.
• Gently swirl each vial until the powder is completely dissolved. The resulting solution is clear and ranges in color from colorless to yellow or green-yellow. FURTHER DILUTION IS REQUIRED prior to administration.
• Store reconstituted, preservative-free product under refrigerated conditions [2-8°C (36-46°F)] for no longer than 24 hours from the time of reconstitution. Discard vial after 24 hours.
• Inspect reconstituted product visually for particulate matter and discoloration prior to further dilution. If particulate matter is observed, discard vial.
• Withdraw the calculated dose of AXTLE from the vial(s) and discard vial with any unused portion.
• Further dilute AXTLE with 5% Dextrose Injection, USP to achieve a total volume of 100 mL for intravenous infusion.
• Store diluted, reconstituted product under refrigerated conditions [2-8°C (36-46°F)] for no more than 24 hours from the time of reconstitution. Discard after 24 hours.