Usual Adult Dose for Non-Small Cell Lung Cancer

500 mg/m2 IV on Day 1 of each 21-day cycle

Comments:

• Limitations of Use: This drug is not indicated for the treatment of patients with squamous cell non-small cell lung cancer (NSCLC)
• With pembrolizumab and platinum chemotherapy for the initial treatment of metastatic nonsquamous NSCLC: This drug should be administered after pembrolizumab and before carboplatin or cisplatin on Day 1 of each 21-day cycle for 4 cycles; after completion of platinum-based therapy, this drug (with or without pembrolizumab) should be administered until disease progression or unacceptable toxicity.
• The manufacturer product information for pembrolizumab and carboplatin or cisplatin should be consulted.
• With cisplatin for initial treatment of locally advanced or metastatic nonsquamous NSCLC: This drug should be administered before cisplatin on Day 1 of each 21-day cycle for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
• As a single agent for maintenance therapy of nonsquamous NSCLC: This drug should be administered until disease progression or unacceptable toxicity after 4 cycles of platinum-based first-line chemotherapy.
• As a single agent for treatment of recurrent nonsquamous NSCLC: This drug should be administered until disease progression or unacceptable toxicity.

• In combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic nonsquamous NSCLC, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma receptor tyrosine kinase (ALK) genomic tumor aberrations
• In combination with cisplatin, for the initial treatment of patients with locally advanced or metastatic, nonsquamous NSCLC
• As a single agent, for the maintenance treatment of patients with locally advanced or metastatic nonsquamous NSCLC whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy
• As a single agent, for the treatment of patients with recurrent, metastatic nonsquamous NSCLC after prior chemotherapy

Usual Adult Dose for Malignant Pleural Mesothelioma

500 mg/m2 IV on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Use: In combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery

Renal Dose Adjustments

CrCl 45 mL/min or greater: No adjustment recommended
CrCl less than 45 mL/min: Not recommended

If renal toxicity develops during therapy: This drug should be withheld until CrCl is 45 mL/min or greater.

Comments:

• CrCl calculated by Cockcroft-Gault equation
• CrCl should be assessed before each cycle; if CrCl is less than 45 mL/min, this drug should not be administered.
• Patients with CrCl between 45 and 79 mL/min: Use of ibuprofen should be avoided for 2 days before, the day of, and 2 days after administration of this drug; patients should be monitored more frequently for myelosuppression, renal toxicity, and gastrointestinal toxicity if concurrent ibuprofen cannot be avoided.

Liver Dose Adjustments

Data not available

Dose Adjustments

CBC should be obtained on Days 1, 8, and 15 of each cycle. Initiation of the next cycle of this drug should be delayed until:

• recovery of nonhematologic toxicity to Grade 0 to 2,
• absolute neutrophil count (ANC) if 1500 cells/mm3 or higher, AND
• platelet count is 100,000 cells/mm3 or higher.

• For dosing modifications for cisplatin, carboplatin, or pembrolizumab, their manufacturer product information should be consulted.

• ANC less than 500 cells/mm3 AND platelets at least 50,000 cells/mm3 OR platelet count less than 50,000 cells/mm3 without bleeding: Dose for next cycle should be 75% of previous dose.
• Platelet count less than 50,000 cells/mm3 with bleeding: Dose for next cycle should be 50% of previous dose.
• Recurrent Grade 3 or 4 myelosuppression after 2 dose reductions: This drug should be discontinued.

• Any Grade 3 or 4 toxicities EXCEPT mucositis or neurologic toxicity OR diarrhea requiring hospitalization: Dose for next cycle should be 75% of previous dose.
• Grade 3 or 4 mucositis: Dose for next cycle should be 50% of previous dose.
• Grade 3 or 4 neurologic toxicity: This drug should be permanently discontinued.
• Recurrent Grade 3 or 4 nonhematologic toxicity after 2 dose reductions: This drug should be permanently discontinued.
• Severe and life-threatening skin toxicity: This drug should be permanently discontinued.
• Interstitial pneumonitis: This drug should be permanently discontinued.

Precautions

CONTRAINDICATIONS:

• History of severe hypersensitivity reaction to the active component

Dialysis

Data not available

Other Comments

Administration advice:

• Administer as an IV infusion over 10 minutes.
• According to at least 1 manufacturer, administer diluted solution via 0.2 micrometer inline filter.

• Vitamin supplementation:
• Start folic acid (400 to 1000 mcg orally once a day) 7 days before the first dose of this drug and continue until 21 days after the last dose of this drug.
• Administer vitamin B12 (1 mg IM) 1 week before the first dose of this drug and every 3 cycles thereafter; subsequent vitamin B12 injections may be administered the same day as treatment with this drug. Do not substitute oral vitamin B12 for IM vitamin B12.
• Corticosteroids: Administer dexamethasone (4 mg orally twice a day) for 3 consecutive days, starting the day before each administration of this drug.

• The manufacturer product information should be consulted.

• Concentrated solutions: Further dilution is required before administration.
• Lyophilized powder: After reconstitution, further dilution is required before administration.
• The manufacturer product information should be consulted.

• Concentrated solution: The manufacturer product information should be consulted.
• Lyophilized powder:
• Compatible: 0.9% Sodium Chloride Injection, USP (preservative-free)
• Do not use calcium-containing solutions for reconstitution.

• This is a hazardous drug; applicable special handling and disposal procedures should be followed.

• Dermatologic: For inflammation/blistering in areas of previous radiation therapy
• Hematologic: CBC (on Days 1, 8, and 15 of each cycle)
• Renal: CrCl (before each dose); renal function (periodically during therapy)

• Read the US FDA-approved patient labeling (Patient Information).
• Take folic acid as directed and keep appointments for vitamin B12 injections to reduce the risk of therapy-related toxicity; corticosteroids are also required.
• Contact physician immediately for signs of infection, fever, bleeding, or symptoms of anemia.
• Contact health care provider immediately for decreased urine output or development of bullous lesions, exfoliation in the skin/mucous membranes, dyspnea, persistent cough, or inflammation/blisters in a previously irradiated area.
• Patients with mild to moderate renal dysfunction: Avoid use of all ibuprofen-containing products for 2 days before, the day of, and 2 days after administration of this drug.
• Patients of childbearing potential: Use effective contraception during therapy and for 6 months after the last dose; inform your prescriber of a known/suspected pregnancy.
• Male patients with partners of childbearing potential: Use effective contraception during therapy and for 3 months after the last dose.
• Do not breastfeed during therapy and for 1 week after the last dose.

Frequently asked questions

• How does pemetrexed work?