PEMETREXED DISODIUM FOR

Adverse Drug Reaction Overview In clinical trials, the most common adverse reactions (incidence ≥ 10%) during therapy with pemetrexed as a single agent were fatigue, nausea, anorexia, anemia, vomiting, stomatitis/pharyngitis, rash/desquamation, diarrhea, leukopenia, and neutropenia.

Additional common adverse reactions (incidence ≥ 10%) during therapy with pemetrexed when used in combination with cisplatin included thrombocytopenia, decreased creatinine clearance, constipation, alopecia, creatinine elevation, and sensory neuropathy.

In clinical trials, sepsis which in some cases was fatal occurred in approximately 1% of patients. In clinical trials, cases of gastrointestinal haemorrhage, ulceration, perforation and necrosis, sometimes fatal, have been reported uncommonly in patients treated with pemetrexed.

Esophagitis/radiation esophagitis has also been uncommonly reported in clinical trials. Supplementation with folic acid and vitamin B12 during treatment with pemetrexed reduces the frequency and severity of hematologic and nonhematologic toxicities.

Clinical Trial Adverse Drug Reactions Malignant Pleural Mesothelioma Combination Use with Cisplatin The following tables list adverse events, considered to be related to pemetrexed disodium, reported in clinical trial patients with MPM treated with 500 mg/m2 of pemetrexed and 75 mg/m2 of cisplatin.

Overall, serious adverse events (SAEs) occurred significantly more frequently in patients on the pemetrexed plus cisplatin arm regardless of drug causality. This was expected because this regimen adds one drug (pemetrexed) to the control regimen (cisplatin).

Among the fully supplemented (FS) subgroup, no single SAE, regardless of drug causality, occurred in > 5% of patients in either arm. Most SAEs were hematologic or gastrointestinal and were expected effects of cytotoxic chemotherapy.

Table 1 displays 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 enrolment in the study (fully supplemented) versus patients who never received vitamin supplementation (never supplemented) during the study in the pemetrexed plus cisplatin arm.

Patients who received supplementation from the start of therapy experienced markedly less laboratory and non-laboratory toxicity compared with patients who never received supplementation. 0). Table 2 provides the frequency and severity of adverse events that have been reported in >5% of 168 patients with MPM who were randomly assigned to receive cisplatin and pemetrexed and 163 patients with mesothelioma randomly assigned to receive single agent cisplatin.