Pemex Special Precautions

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 (see Dosage & Administration). In clinical studies, less overall toxicity and reductions in Grade 3/4 hematologic and nonhematologic toxicities such as neutropenia, febrile neutropenia, and infection with Grade 3/4 neutropenia were reported when pretreatment 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 (see Dosage & Administration).
Bone Marrow Suppression: Pemetrexed can suppress bone marrow function, as manifested by neutropenia, thrombocytopenia, and anemia (or pancytopenia) (see Adverse Reactions); myelosuppression is usually the dose-limiting toxicity. Dose reductions for subsequent cycles are based on nadir ANC, platelet count, and maximum nonhematologic toxicity seen in the previous cycle (see Dosage & Administration).
Decreased Renal Function: Pemetrexed is primarily eliminated unchanged by renal excretion. Decreased renal function can result in the decreased clearance and increased exposure (AUC) (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions). 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 (see Dosage & Administration).
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 combined with other drug or alone administrated, there was reported severe kidney accident, including acute renal failure. Many patients with the accidents have potential risk, including dehydration or original hypertension or diabetes mellitus. No study was conducted on Cisplatin with Pemetrexed administrated on patients with moderate renal impairment.
Use with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) with Mild to Moderate Renal Insufficiency: Caution should be taken when administering NSAIDs (including ibuprofen) concurrently with Pemetrexed to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min) (see Interactions).
Liver Function impairment: High AST, ALT or total bilirubin can't influence the pharmacokinetics of Pemetrexed (see Pharmacology: Pharmacokinetics under Actions).
About liver function impairment in receiving Pemetrexed, the dosage adjustment see in Table 2 previously (see Dosage & Administration).
Required Laboratory Monitoring: Patients should not begin a new cycle of treatment unless the ANC is ≥1500 cells/mm³, the platelet count is ≥100,000 cells/mm³, and creatinine clearance is ≥45 mL/min (see Dosage & Administration).
Pregnancy Category D: Based on its mechanism of action, Pemetrexed can cause fetal harm when administered to a pregnant woman. Pemetrexed administered intraperitoneally to mice during organogenesis was embryotoxic, fetotoxic and teratogenic in mice at greater than 1/833 the recommended human dose. If Pemetrexed is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Women should be advised to use effective contraceptive measures to prevent pregnancy during treatment with Pemetrexed (see Use Pregnancy & Lactation).
Pemetrexed can cause heredity toxicity. It is recommended that patients do not father a child during the treatment or within 6 months after the treatment. It is recommended to take contraceptive measures or avoid sexual activities. It is recommended to consider human sperm preservation before the treatment.
Gender: In the first-line treatment of non-small cell lung cancer trial, 70% of patients were males and 30% were females. The HR for overall survival was 0.97 (95% CI: 0.85, 1.10) for males and 0.86 (95% CI: 0.70, 1.06) for females in the intent to treat population.
In the maintenance non-small cell lung cancer trial, 73% of patients were males and 27% females. The HR for overall survival was 0.78 (95% CI: 0.63, 0.96) for males and was 0.83 (95% CI: 0.56, 1.21) for females in the intent to treat population.
In the second-line treatment of non-small cell lung cancer trial, 72% of patients were males and 28% females. The HR for overall survival was 0.95 (95% CI: 0.76, 1.19) for males and HR was 1.28 (95% CI: 0.86, 1.91) for females in the intent to treat population.
In the mesothelioma trial, 82% of patients were males and 18% females. The HR for overall survival was 0.85 (95% CI: 0.66, 1.09) in males and was 0.48 (95% CI: 0.27, 0.85) in females in the intent to treat population.
Race: In the first-line treatment of non-small cell lung cancer trial, 78% of patients were Caucasians, 13% East/Southeast Asians, and 9% others. For Caucasians, the HR for overall survival was 0.92 (95% CI: 0.82, 1.04), for East/Southeast Asians the HR was 0.86 (95% CI: 0.61, 1.21), and for others the HR was 1.24 (95% CI: 0.84, 1.84) in the intent to treat population.
In the maintenance non-small cell lung cancer trial, 65% of patients were Caucasians, 23% East Asian, and 12% others. For Caucasians the HR for overall survival was 0.77 (95% CI: 0.62, 0.97), for East Asians was 1.05 (95% CI: 0.70, 1.59) and for others the HR was 0.46 (95% CI: 0.26, 0.79) in the intent-to-treat population.
In the second-line treatment of non-small cell lung cancer trial, 71% of patients were Caucasians and 29% others. For Caucasians the HR for overall survival was 0.91 (95% CI: 0.73, 1.15) and for others the HR was 1.27 (95% CI: 0.87, 1.87) in the intent to treat population.
In the mesothelioma trial, 92% of patients were Caucasians and 8% others. For Caucasians, the HR for overall survival was 0.77 (95% CI: 0.61, 0.97) and for others the HR was 0.86 (95% CI: 0.39, 1.90) in the intent to treat population.
Other: Because Pemetrexed co-administrate with Cisplatin has gastrointestinal toxic, even observe severe dehydration. Therefore, patients should receive adequate antiemetic and appropriate hydration before treatment and/or after treatment.
In Pemetrexed clinical research, few serious reports of cardiovascular accident including myocardial and cerebrovascular events were reported, except Pemetrexed was treated combination with other cytotoxic drugs. Most of patients who reported these accidents have known the cardiovascular risk.
Patients with radiotherapy before, during or after Pemetrexed treatment, were reported to radiation pneumonitis. Especially for these patients, it should be caution for using radical sensitizer. In the report of patients with radiotherapy several weeks ago or a few years ago, there is case of radical reminiscence injury.
Use in Children: The safety and effectiveness of pemetrexed for pediatric patients are unknown.
Use in Elderly: Pemetrexed is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Renal function monitoring is recommended with administration of Pemetrexed. No dose reductions other than those recommended for all patients are necessary for patients 65 years of age or older (see Dosage & Administration).
In the first-line of treatment non-small cell lung cancer clinical trial, 37.7% of patients treated with Pemetrexed plus Cisplatin were ≥65 years and Grade 3/4 neutropenia was greater as compared to patients <65 years (19.9% versus 12.2%). For patients <65 years, the HR for overall survival was 0.96 (95% CI: 0.83, 1.10) and for patients ≥65 years the HR was 0.88 (95% CI: 0.74, 1.06) in the intent to treat population.
In the maintenance non-small cell lung cancer trial 33.3% of patients treated with Pemetrexed were ≥65 years and no differences were seen in Grade 3/4 adverse reactions as compared to patients <65 years. For patients <65 years, the HR for overall survival was 0.74 (95% CI: 0.58, 0.93) and for patients ≥65 years the HR was 0.88 (95% CI: 0.65, 1.21) in the intent to treat population.
In the second-line treatment of non-small cell lung cancer trial, 29.7% patients treated with Pemetrexed were ≥65 years and Grade 3/4 hypertension was greater as compared to patients <65 years. For patients <65 years, the HR for overall survival was 0.95 (95% CI: 0.76, 1.19), and for patients ≥65 years the HR was 1.15 (95% CI: 0.79, 1.68) in the intent to treat population.
The mesothelioma trial included 36.7% patients treated with Pemetrexed plus cisplatin that were ≥65 years, and Grade 3/4 fatigue, leukopenia, neutropenia, and thrombocytopenia were greater as compared to patients <65 years. For patients <65 years, the HR for overall survival was 0.71 (95% CI: 0.53, 0.96) and for patients ≥65 years, the HR was 0.85 (95% CI: 0.59, 1.22) in the intent to treat population.