Pemetrexed

Pemetrexed may cause severe myelosuppression, including anemia, neutropenia, thrombocytopenia and/or pancytopenia; frequent laboratory monitoring is necessary (myelosuppression is often dose-limiting). Severe myelosuppression may require blood transfusion. Prophylactic folic acid and vitamin B12 supplements are necessary to reduce hematologic toxicity, febrile neutropenia and infection; initiate supplementation 1 week before the first dose of pemetrexed and continue for 21 days after the last pemetrexed dose (the risk for myelosuppression is higher in patients who did not receive vitamin supplementation). Monitor blood counts at the beginning of each cycle, and as clinically indicated. Dose reductions in subsequent cycles may be required due to myelosuppression.

Serious and occasionally fatal dermatologic toxicity may occur; pretreatment with dexamethasone is necessary to reduce the incidence and severity of cutaneous reactions. Rarely, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Permanently discontinue pemetrexed for severe and life-threatening bullous, blistering, or exfoliating dermatologic toxicity.

Gastrointestinal toxicity may occur; prophylactic folic acid and vitamin B12 supplements are necessary to reduce gastrointestinal toxicity. Initiate supplementation 1 week before the first dose of pemetrexed and continue for 21 days after the last pemetrexed dose.

Hypersensitivity (including allergic reaction) has been reported with pemetrexed.

Pemetrexed may cause severe (and potentially fatal) renal toxicity (renal toxicity may occur with single-agent pemetrexed or when used in combination with other chemotherapy agents). Measure creatinine clearance prior to each dose and monitor renal function throughout treatment. May require therapy discontinuation. Withhold pemetrexed treatment for creatinine clearance • Pulmonary toxicity: Interstitial pneumonitis has been observed with use; may be serious and/or fatal. Interrupt therapy and evaluate promptly for acute onset new or progressive pulmonary symptoms (eg, dyspnea, cough, or fever). If interstitial pneumonitis is confirmed, permanently discontinue pemetrexed.

Radiation recall may occur in patients administered pemetrexed who received radiation previously (weeks to years). Monitor for inflammation or blistering in areas of prior radiation treatment; permanently discontinue pemetrexed if radiation recall is confirmed. Disease-related concerns:

Pemetrexed is primarily cleared by the kidneys; decreased renal function results in increased toxicity. The manufacturer does not recommend use if CrCl • Third space fluid: Although the effect of third space fluid on pemetrexed pharmacokinetics has not been fully defined, studies have determined pemetrexed concentrations in patients with mild-to-moderate ascites/pleural effusions were similar to concentrations in trials of patients without third space fluid accumulation. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Ibuprofen may reduce the clearance of pemetrexed. In patients with CrCl 45 to 79 mL/minute, interrupt ibuprofen therapy 2 days prior to, during, and 2 days after pemetrexed therapy. If concomitant use cannot be avoided, monitor for myelosuppression, renal, and gastrointestinal toxicity.