Pemrydi RTU Dosage

Recommended Dosage for Non-Squamous NSCLC

• The recommended dose of PEMRYDI RTU when administered with pembrolizumab and platinum chemotherapy for the initial treatment of metastatic non-squamous NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes administered after pembrolizumab and prior to carboplatin or cisplatin on Day 1 of each 21-day cycle for 4 cycles. Following completion of platinum-based therapy, treatment with PEMRYDI RTU with or without pembrolizumab is administered until disease progression or unacceptable toxicity. Please refer to the full prescribing information for pembrolizumab and for carboplatin or cisplatin.
• The recommended dose of PEMRYDI RTU 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/m2 as 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 PEMRYDI RTU 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/m2 as 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 PEMRYDI RTU 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/m2 as 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 PEMRYDI RTU when administered with cisplatin in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 as an intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Renal Impairment

• PEMRYDI RTU dosing recommendations are provided for patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater [see Dosage and Administration (2.1, 2.2)]. There is no recommended dose for patients whose creatinine clearance is less than 45 mL/min [see Use in Specific Populations (8.6)].

Premedication and Concomitant Medications to Mitigate Toxicity

Vitamin Supplementation

• Initiate folic acid 400 mcg to 1,000 mcg orally once daily, beginning 7 days before the first dose of PEMRYDI RTU and continuing until 21 days after the last dose of PEMRYDI RTU [see Warnings and Precautions (5.1)].
• Administer vitamin B12, 1 mg intramuscularly, 1 week prior to the first dose of PEMRYDI RTU and every 3 cycles thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with PEMRYDI RTU [see Warnings and Precautions (5.1)]. Do not substitute oral vitamin B12 for intramuscular vitamin B12.

Corticosteroids

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

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

In patients with creatinine clearances between 45 mL/min and 79 mL/min, modify administration of ibuprofen as follows [see Warnings and Precautions (5.6), Drug Interactions (7) and Clinical Pharmacology (12.3)]:

• Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of PEMRYDI RTU.
• 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 PEMRYDI RTU if the creatinine clearance is less than 45 mL/min.

Delay initiation of the next cycle of PEMRYDI RTU until:

• recovery of non-hematologic toxicity to Grade 0-2,
• absolute neutrophil count (ANC) is 1,500 cells/mm3 or higher, and
• platelet count is 100,000 cells/mm3 or higher.

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

For dosing modifications for cisplatin, carboplatin, or pembrolizumab, refer to their prescribing information.

Table 1: Recommended Dosage Modifications for Adverse Reactionsa

Preparation for Administration

PEMRYDI RTU is a hazardous drug. Follow applicable special handling and disposal procedures.1

• Calculate the dose of PEMRYDI RTU and determine the volume of needed PEMRYDI RTU. Each vial contains an excess of PEMRYDI RTU to facilitate delivery of labeled amount.
• Withdraw the calculated dose of PEMRYDI RTU from the vial(s) and discard the vial(s) with any unused portion.
• Transfer the calculated dose into an empty intravenous bag. Do NOT further dilute PEMRYDI RTU.
• Visually inspect for particulate matter and discoloration prior to administration. Discard if particulate matter or discoloration is observed.
• Immediately administer PEMRYDI RTU undiluted, as an intravenous infusion over 10 minutes using an infusion pump.