Malignant Pleural Mesothelioma — In Table 5 adverse events occurring in at least 5% of patients are shown along with important effects (renal failure, infection) occurring at lower rates. Adverse events equally or more common in the cisplatin group are not included. The adverse effects more common in the ALIMTA group were primarily hematologic effects, fever and infection, stomatitis/pharyngitis, and rash/desquamation.

Table 5: Adverse Events* in Fully Supplemented Patients Receiving ALIMTA plus Cisplatin in MPM CTC Grades (% incidence)

Table 6 compares the incidence (percentage of patients) of CTC Grade 3/4 toxicities in patients who received vitamin supplementation with daily folic acid and vitamin B₁₂ from the time of enrollment in the study (fully supplemented) with the incidence in patients who never received vitamin supplementation (never supplemented) during the study in the ALIMTA plus cisplatin arm.

Table 6: Selected Grade 3/4 Adverse Events Comparing Fully Supplemented versus Never Supplemented Patients in the ALIMTA plus Cisplatin arm in MPM (% incidence)

The following adverse events were greater in the fully supplemented group compared to the never supplemented group: hypertension (11%, 3%), chest pain (8%, 6%), and thrombosis/embolism (6%, 3%).

For fully supplemented patients treated with ALIMTA plus cisplatin, the incidence of CTC Grade 3/4 fatigue, leukopenia, neutropenia, and thrombocytopenia were greater in patients 65 years or older as compared to patients younger than 65. No relevant effect for ALIMTA safety due to gender or race was identified, except an increased incidence of rash in men (24%) compared to women (16%).

Non-Small Cell Lung Cancer (NSCLC)—Table 7 provides the clinically relevant undesirable effects that have been reported in 265 patients randomly assigned to receive single-agent ALIMTA with folic acid and vitamin B₁₂ supplementation and 276 patients randomly assigned to receive single-agent docetaxel. All patients were diagnosed with locally advanced or metastatic NSCLC and had received prior chemotherapy.

Table 7: Adverse Events* in Patients Receiving ALIMTA vs. Docetaxel in NSCLC CTC Grades (% incidence)

Clinically relevant Grade 3 and Grade 4 laboratory toxicities were similar between integrated Phase 2 results from three single-agent ALIMTA studies (N=164) and the Phase 3 single-agent ALIMTA study described above, with the exception of neutropenia (12.8% versus 5.3%, respectively) and alanine transaminase elevation (15.2% versus 1.9%, respectively). These differences were likely due to differences in the patient population, since the Phase 2 studies included chemonaive and heavily pretreated breast cancer patients with pre-existing liver metastases and/or abnormal baseline liver function tests.

The incidence of CTC Grade 3/4 hypertension was the only finding demonstrating an age difference in patients treated with ALIMTA and was greater in patients 65 years or older as compared to younger patients. There are insufficient numbers of non-white patients to assess ethnic differences. The incidence of CTC Grade 3/4 dyspnea was higher in males for both treatment arms.

Post-marketing experience: The following adverse events have been identified during post-approval use of ALIMTA. These events have occurred with ALIMTA when used as a single-agent and in combination therapies. Decisions to include these events are based on the seriousness of the event, frequency of reporting, or potential causal connection to ALIMTA.

Gastrointestinal — Rare cases of colitis have been reported in patients treated with ALIMTA.

ALIMTA is primarily eliminated unchanged renally as a result of glomerular filtration and tubular secretion. Concomitant administration of nephrotoxic drugs could result in delayed clearance of ALIMTA. Concomitant administration of substances that are also tubularly secreted (e.g., probenecid) could potentially result in delayed clearance of ALIMTA.

Although ibuprofen (400 mg qid) can be administered with ALIMTA in patients with normal renal function (creatinine clearance ≥80 mL/min), caution should be used when administering ibuprofen concurrently with ALIMTA 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 of 2 days before, the day of, and 2 days following administration of ALIMTA.

In the absence of data regarding potential interaction between ALIMTA 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 ALIMTA administration. If concomitant administration of an NSAID is necessary, patients should be monitored closely for toxicity, especially myelosuppression, renal, and gastrointestinal toxicity.

Drug/Laboratory Test Interactions

None known.

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