Adult Dosing

Nonsquamous non-small cell lung cancer and malignant pleural mesothelioma

Combination with cisplatin

• 500 mg/m² IV over 10 minutes on day 1 of each 21 day cycle
• Infuse cisplatin 75 mg/m² over 2hrs beginning approximately 30 minutes after administration of pemetrexed

Nonsquamous non-small cell lung cancer

Single use agent

• 500 mg/m² IV over 10 minutes on day 1 of each 21 day cycle

• Instruct patients treated with pemetrexed to take a low-dose oral folic acid preparation or multivitamin with folic acid on a daily basis and provide adequate hydration
• Administer atleast 5 daily doses of folic acid during the 7-day period preceding the first dose of pemetrexed
• Continue during the full course of therapy and for 21 days after the last dose of pemetrexed
• Administer IM vitamin B12 during the week preceding the first dose of pemetrexed and q3 cycles thereafter, subsequent IM vitamin B12 injections may be given the same day as pemetrexed
• Pretreat patients with dexamethasone (or equivalent) to reduces the incidence and severity of cutaneous reaction
• Perform complete blood cell counts, including platelet counts in patients receiving pemetrexed, monitor for nadir and recovery before each dose and on days 8 and 15 of each cycle
• If ANC 1500 cells/mm³, platelet count 100,000 cells/mm³ and creatinine clearance 45 mL/min, begin with a new cycle of treatment
• Modification based on toxicity
• Hematological toxicities (single dose or in combination and cisplatin)
• Nadir Platelets 50,000/mm³, Nadir ANC < 500/mm³: 75% of previous dose
• Nadir Platelets < 50,000/mm³ without bleeding regardless of Nadir ANC: 75% of previous dose
• Nadir Platelets < 50,000/mm³, with bleeding regardless of Nadir ANC: 50% of previous dose
• Nonhematologic toxicities (single dose or in combination and cisplatin)
• Grade3/4 nonhematologic toxicities (excluding neurotoxicity) except mucositis: 75% of previous dose
• Diarrhea requiring hospitalization or Grade 3/4 diarrhea: 75% of previous dose
• Grade 3/4 mucositis: 50% of previous dose (pemetrexed mg/m² ) and 100% of previous dose (cisplatin)mg/m²
• Neurotoxicity (single dose or in combination and cisplatin)
• 0-1 CTC grade: 100% of previous dose
• 2 CTC grade: 100% of previous dose (pemetrexed mg/m² ) and 50% of previous dose (cisplatin)mg/m²

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Locally advanced or metastatic nonsquamous non-small cell lung cancer
• Initial treatment in combination with cisplatin
• Maintenance therapy for patients for whom disease has not progressed after treatment with four cycles of platinum-based first-line chemotherapy
• Post chemotherapy as a single agent

• For treatment of mesothelioma in combination with cisplatin

• Hypersensitivity to any of the ingredients of the product
• Treatment of squamous cell non-small cell lung cancer
• CrCl <45 mL/min
• Absolute neutrophil count <1500 cells/mm³
• Plt <100,000 cells/mm³
• Pregnancy
• Breastfeeding

• N/A

Renal Dose Adjustment (Based on CrCl)

• >45 mL/min: No dose adjustments
• <45 mL/min: Contraindicated

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

• Instruct patients to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related hematologic and GI toxicity
• Skin rash have occurred in patients not pretreated with a corticosteroid
• Provide pretherapy with corticosteroid to avoid skin rash and pretherapy with dexamethasone to reduce incidence and severity of cutaneous reaction
• Suppression of bone marrow function manifested by neutropenia, thrombocytopenia, myelosuppression and anemia have occurred
• Reduce doses for subsequent cycles based on nadir ANC, platelet count, and maximum nonhematologic toxicity seen in the previous cycle
• Avoid administering in patients with creatinine clearance <45 mL/min
• Treat patients with severe renal impairment (creatinine clearance 19 mL/min) with folic acid and vitamin B12 to avoid fatal death related to toxicity
• Avoid concomitant use of ibuprofen in patients with mild to moderate renal impairment (creatinine clearance from 45 to 79 mL/min)
• Monitor BUN or creatinine, LFTs periodically; CBC w/ differential count, platelets prior to each dose, then on days 8 and 15 of each cycle
• Discontinue treatment if a patient experiences any hematologic or nonhematologic Grade 3 or 4 toxicity after 2 dose reductions or immediately if Grade 3 or 4 neurotoxicity is observed

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Myelosuppression
• Pleural effusion
• Concurrent NSAIDs
• Ascites (drainage recommended before starting therapy )
• Pleural effusions (drainage recommended before starting therapy )

Pregnancy Category:D

Breastfeeding: Unsafe; Manufacturer advises to avoid during pregnancy due to potential hazards to fetus. Use effective contraceptives to prevent pregnancy during use of this drug.

• CV: Hypertension, thrombosis, thromboembolism, chest pain
• GI: Dehydration, mucositis, dyspepsia, constipation, nausea, stomatitis, vomiting, anorexia, diarrhea, esophagitis, mouth pain
• RESP: Pharyngitis
• DERM: Erythema multiforme, pruritus, alopecia, desquamation, rash
• HEMA: Pancytopenia, anemia, leukopenia, thrombocytopenia, neutropenia, febrile neutropenia
• EENT: Conjunctivitis
• HEPA: Elevated liver transaminases
• GU: Renal failure, elevated Cr
• NEURO: Sensory neuropathy, taste disturbance
• MISC: Fever, infections, hypersensitivity reaction, radiation recall, fatigue

• Folic acid antagonist; disrupts folate-dependent metabolic processes essential for cell replication
• IV administration results in complete bioavailability
• Minimally metabolized by liver
• Renally excreted (70-90% unchanged)
• Half-life: 3.5 hrs

US Trade Name(s)

• Alimta

US Availability

Alimta

• PWDR for INJ: 100 mg/vial
• PWDR for INJ: 500 mg/vial

Canadian Trade Name(s)

• Alimta

Canadian Availability

Alimta

• PWDR for INJ: 100 mg/vial
• PWDR for INJ: 500 mg/vial

UK Trade Name(s)

• Alimta

UK Availability

Alimta

• PWDR for INJ: 100 mg/vial
• PWDR for INJ: 500 mg/vial

Australian Trade Name(s)

• Alimta

Australian Availability

Alimta

• PWDR for INJ: 100 mg/vial
• PWDR for INJ: 500 mg/vial

[Outline]

Hematology/Oncology

Antineoplastics

Antimetabolites