Pemetrexed Cisplatin

Uses w/ cisplatin in nonresectable mesothelioma NSCLC Action Antifolate antineoplastic Dose 500 mg/m IV over 10 min q3wk hold if CrCl <45 mLAnin give w/ vit Bi2 (1000 meg IM q9wk) folic acid (350-1000 meg PO daily) start 1 wk before dexamethasone 4 mg PO bid x 3 start 1 d before each Rx Caution [D, -] w/ renal/hepatic/ BM impair Contra Component sensitivity Disp IV SE Neutropenia, thrombocytopenia, N/V/D, anorexia, stomatitis, renal failure, neuropathy, fevCT, fatigue, mood changes, dyspnea, anaphylactic Rxns Interactions t Effects W/ NSAIDs, probenecid d/t decreased pemetrexed EMS Monitor for S/Sxs of Infxn OD May cause profound BM suppression, mucous membrane irritation, D, and rash symptomatic and supportive... 

Pemetrexed is a folic-acid antagonist that disrupts folate-dependent metabolic processes essential for cell replication. It is indicated 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 and as a single agent for the treatment of locally advanced or metastatic non-small-cell lung cancer after prior chemotherapy. 

The only FDA-approved indication for pemetrexed is for second-line therapy in mesothelioma it also is used, however, for refractory non—small cell lung cancer. Promising results have been published in first-line use with cisplatin in both tumors. 

Pemetrexed (Fig. 42.25) is a novel multitarget antifolate used by the IV route for the treatment of advanced or metastatic nonsmall cell lung cancer and in combination with cisplatin in malignant pleural mesothelioma. 

The US manufacturers state that there is no pharmacokinetic interaction between pemetrexed and cisplatin, but there is the possibility that cispla-tin-induced nephrotoxicity could decrease pemetrexed clearance and increase its toxicity. However, it should be noted that the use of pemetrexed with cisplatin is indicated for mesothelioma. - ... 

The manufacturers consider that the eoneurrent use of nephrotoxic drugs could potentially decrease the elearanee of pemetrexed and therefore increase its toxicity. - In the UK, the manufacturer specifically mentions aminoglycosides, loop diuretics, platinum compounds (see also (a) cisplatin above) and ciciosporin, and recommends caution with combined use, and, if necessary, close monitoring of creatinine clearance. ... 

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