Contraindication
Pemetrexed is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed or to any other ingredient used in the formulation.

Warnings
Patients must be instructed to take folic acid and vitamin B12 with Pemetrexed as a prophylaxis to reduce treatment-related hematologic and GI toxicity.

Pemetrexed should not be administered to patients with a creatinine clearance <45 mL/min. One patient with severe renal impairment (creatinine clearance 19 mL/min) who did not receive folic acid and vitamin B12 died of drug-related toxicity following administration of Pemetrexed alone.

Pemetrexed can suppress bone marrow function, as manifested by neutropenia, thrombocytopenia, and anemia.

Pregnancy Category D—Pemetrexed may cause fetal harm when administered to a pregnant woman.

Precautions
Complete blood cell counts, including platelet counts and periodic chemistry tests, should be performed on all patients receiving Pemetrexed.

Patients should not begin a new cycle of treatment unless the ANC is ≥ 1500 cells/mm3 and the platelet count is ≥ 100,000 cells/mm3.

Pretreatment with dexamethasone or its equivalent has been reported to reduce the incidence and severity of skin rash.

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.

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). Patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination half-lives for a period for 2 days before, the day of, and 2 days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives, all patients taking these NSAIDs should interrupt dosing for at least 5 days before, the day of, and 2 days following pemetrexed administration. If concomitant administration of an NSAID is necessary, patients should be monitored closely for toxicity, especially myelosuppression, renal and gastrointestinal toxicity.

Concomitant administration of nephrotoxic drugs or substances that are tubularly secreted could result in delayed clearance of pemetrexed.

It is recommended that nursing be discontinued if the mother is being treated with pemetrexed.

Pemetrexed should be administered under the supervision of a qualified physician experienced in the use of antineoplastic agents.

Dose adjustments may be necessary in patients with hepatic insufficiency.

Dosing and Modification Guidelines

Complete blood cell counts, including platelet counts and periodic chemistry tests, should be performed on all patients receiving pemetrexed.

Patients should not begin a new cycle of treatment unless the ANC is ≥ 1500 cells/mm3 and the platelet count is ≥ 100,000 cells/mm3.

Dose adjustments at the start of a subsequent cycle should be based on nadir hematologic counts or maximum nonhematologic toxicity from the preceding cycle of therapy. Modify or suspend therapy according to the Dosage Reduction Guidelines in the full Prescribing Information.

Pemetrexed has shown safety advantages over docetaxel
The effect of Pemetrexed on survival is reasonably likely based on response rate.*

Patients receiving Pemetrexed experienced lower rates of:

• Neutropenia
• Neutropenic fever
• Neutropenia with infection
• Alopecia
• Grades 3/4 diarrhea

Patients receiving Pemetrexed experienced a significant increase in ALT.

* In the second line NSCLC setting, docetaxel has demonstrated overall survival compared with the best supportive care. Controlled trials demonstrating survival benefit of Pemetrexed are still ongoing.

Source: http://www.lillyoncology.com/professionals/Pemetrexed_nsclc_safety_info.jsp?reqNavId=1.6.3