Pemeta-100/Pemeta-500 Special Precautions

Premedication Regimen: Need for Folate and Vitamin B12 Supplementation: Patients treated with Pemetrexed must be instructed to take folic acid and vitamin B12 as a prophylactic measure to reduce treatment-related hematologic and GI toxicity. In clinical studies, less overall toxicity and reductions in Grade 3/4 hematologic and non-hematologic toxicities such as neutropenia, febrile neutropenia, and infection with Grade 3/4 neutropenia, febrile neutropenia, and infection with Grade 3/4 neutropenia were reported when pre-treatment with folic acid and vitamin B12 was administered.
Corticosteroid Supplementation: Skin rash has been reported more frequently in patients not pretreated with a corticosteroid in clinical trials. Pretreatment with dexamethasone (or equivalent) reduces the incidence and severity of cutaneous reaction.
Bone Marrow Suppression: Pemetrexed can suppress bone marrow function, as manifested by neutropenia, thrombocytopenia, and anemia (or pancytopenia); myelosuppression is usually the dose-limiting toxicity. Dose reductions for subsequent cycles are based on nadir ANC, platelet count, and maximum non-hematologic toxicity seen in the previous cycle.
Decreased Renal Function: Pemetrexed is primarily eliminated unchanged by renal excretion. No dosage adjustment is needed in patients with creatinine clearance >45 mL/min. Insufficient numbers of patients have been studied with creatinine clearance <45 mL/min to give a dose recommendation. Therefore, Pemetrexed should not be administered to patients whose creatinine clearance is <45 mL/min.
One patient with severe renal impairment (creatinine clearance 19 mL/min) who did not receive folic acid and vitamin B12.
Use with non-steroidal anti-inflammatory drugs with mild to moderate renal insufficiency: Caution should be used when administering ibuprofen concurrently with pemetrexed to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min). Other NSAIDs should also be used with caution.
Required Laboratory Monitoring: Patients should not begin a new cycle of treatment unless the ANC >1500 cells/mm³, the platelet count is >100,000 cells/mm³, and creatinine clearance is >45 mL/min.
Third space fluid: The effect of third space fluid, such as pleural effusion and ascites, on Pemetrexed is unknown. In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to Pemetrexed administration.