Trade Names:Alimta- Injection, lyophilized powder for solution 100 mg- Injection, lyophilized powder for solution 500 mg
Disrupts folate-dependent metabolic processes that are essential for cell replication.
Vd is about 16.1 L. Protein binding is approximately 81%.
Not appreciably metabolized.
Primarily eliminated in the urine. Elimination half-life is 3.5 h.
Cl decreases and AUC increases as renal function decreases.Hepatic Function Impairment
Studies have not been conducted. However, elevated ALT, AST, or total bilirubin did not alter the pharmacokinetics.Elderly
Pharmacokinetics not affected by age.Gender
Pharmacokinetics not affected by gender.Race
Pharmacokinetics similar in white and black patients. No data are available for other ethnic groups.
In combination with cisplatin for the treatment of malignant pleural mesothelioma in patients whose disease is unresectable or who are otherwise not candidates for curative surgery; as a single agent for the initial treatment of locally advanced or metastatic non–small cell lung cancer after prior chemotherapy; in combination with cisplatin for the treatment of locally advanced or metastatic nonsquamous non–small cell lung cancer; for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non–small cell lung cancer whose disease has not progressed after 4 cycles of platinum-based first-line chemotherapy.
IV Recommended dose is 500 mg/m 2 infused over 10 min on day 1 of each 21-day cycle.Dosage ModificationAdults
IV Reduce the dose of pemetrexed to 75% of previous dose in patients with nadir absolute neutrophil count (ANC) less than 500/mm 3 and nadir platelets of at least 50,000/mm 3 , nadir platelets less than 50,000/mm 3 without bleeding regardless of nadir ANC, any grade 3 or 4 toxicities (except mucositis), or any diarrhea requiring hospitalization or grade 3 or 4 diarrhea. Reduce the dose to 50% of previous dose in patients with nadir platelets less than 50,000/mm 3 with bleeding regardless of nadir ANC or grade 3 or 4 mucositis. Discontinue immediately if grade 3 or 4 neurotoxicity occurs or if a patient experiences any hematologic or nonhematologic grade 3 or 4 toxicity after 2 dose reductions.
Store unopened vials at 59° to 86°F. Reconstituted solution should be used immediately or within 24 h if stored in refrigerator (36° to 46°F) or at controlled room temperature. Discard solution if not used within 24 h.
May delay Cl of pemetrexed.NSAIDs with longer half-lives (or NSAIDs with short elimination half-lives in patients with mild to moderate renal insufficiency)
Patients should interrupt NSAID dosing for at least 5 days before (2 days for NSAIDs with short elimination half-lives in patients with mild to moderate renal insufficiency), the day of, and 2 days following pemetrexed administration. If coadministration of an NSAID is necessary, closely monitor for toxicity, especially myelosuppression and renal and GI toxicity.
None well documented.
Supraventricular arrhythmia (less than 1%).
Fatigue (34%); sensory neuropathy (9%); motor neuropathy (1% to 5%).
Rash/desquamation (14%); pruritus (7%); alopecia (6%); erythema multiforme (1% to 5%).
Increased lacrimation, ocular surface disease including conjunctivitis (1% to 5%).
Nausea (31%); anorexia (22%); vomiting (16%); stomatitis/pharyngitis (15%); diarrhea (13%); mucositis/stomatitis (7%); constipation (6%); abdominal pain (1% to 5%); colitis (postmarketing).
CrCl decreased, creatinine increased, glomerular filtration rate decreased (1% to 5%); renal failure (less than 1%).
Anemia (19%); leukopenia (12%); neutropenia (11%); thrombocytopenia (8%); febrile neutropenia (1% to 5%).
Increased ALT (10%); increased AST (8%).
Allergic reactions/hypersensitivity (1% to 5%).
Interstitial pneumonitis (postmarketing).
Fever (8%); infection (5%); edema (1% to 5%); radiation recall (postmarketing).
Assess CBC with differential and platelet count before starting therapy, on days 8 and 15 of each cycle, and before starting new cycle. Do not begin a new cycle unless ANC is at least 1,500/mm 3 , platelet count is at least 100,000/mm 3 , and CrCl is at least 45 mL/min. Perform periodic chemistry tests to evaluate renal and hepatic function.
Category D .
Safety and efficacy not established.
Use with caution because of the increased likelihood of decreased renal function.
Do not administer to patients with CrCl less than 45 mL/min.
Suppression of bone marrow function, manifested by neutropenia, thrombocytopenia, and anemia (or pancytopenia), may occur.
Pretreat with corticosteroids (eg, dexamethasone) to reduce incidence and severity of cutaneous reactions.
Folic acid and vitamin B 12 supplementation should be taken to reduce treatment-related hematologic and GI toxicity. Ensure patient is taking low-dose folic acid supplement or multivitamin containing folic acid daily, starting 7 days before first dose of pemetrexed, during treatment, and for 21 days following last dose of pemetrexed. Ensure patient receives 1 IM injection of vitamin B 12 during the week preceding the first dose of pemetrexed and then every 3 cycles thereafter. Subsequent doses may be administered the same day as pemetrexed.
Coadminister NSAIDs with caution to patients with mild to moderate renal insufficiency.
Consider draining third-space fluid (eg, pleural effusion and ascites) prior to administering pemetrexed.
Anemia, diarrhea, infection (with or without fever), mucositis, neutropenia, rash, thrombocytopenia.
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