Pexitaz Drug Interactions

Pemetrexed is mainly eliminated unchanged renally by tubular secretion and to a lesser extent by glomerular filtration. Concomitant administration of nephrotoxic drugs (e.g., aminoglycoside, loop diuretics, platinum compounds, cyclosporin) could potentially result in delayed clearance of pemetrexed. This combination should be used with caution. If necessary, creatinine clearance should be closely monitored.
Concomitant administration of substances that are also tubularly secreted (e.g., probenecid, penicillin) could potentially result in delayed clearance of pemetrexed. Caution should be made when these drugs are combined with pemetrexed. If necessary, creatinine clearance should be closely monitored.
In patients with normal renal function (creatinine clearance ≥80 ml/min), high doses of nonsteroidal anti-inflammatory drugs (NSAIDs, such as ibuprofen >1,600 mg/day) and aspirin at higher dosage (≥1.3 g daily) may decrease pemetrexed elimination and, consequently, increase the occurrence of pemetrexed adverse events. Therefore, caution is advised when administering higher doses of NSAIDs or aspirin at higher dosage concurrently with pemetrexed to patients with normal function (creatinine clearance ≥80 ml/min).
In patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 ml/min), the concomitant administration of pemetrexed with NSAIDs (e.g., ibuprofen) or aspirin at higher dosage should be avoided for 2 days before, on the day of, and 2 days following pemetrexed administration.
In the absence of data regarding potential interaction with NSAIDs having longer half-lives, such as piroxicam or rofecoxib, the concomitant administration with pemetrexed should be avoided for at least 5 days prior to, on the day, and at least 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.
Pemetrexed undergoes limited hepatic metabolism. Results from in vitro studies with human liver microsomes indicated that pemetrexed would not be predicted to cause clinically significant inhibition of the metabolic clearance of drugs metabolised by CYP3A, CYP2D6, CYP2C9, and CYP1A2. No studies were conducted to determine the cytochrome P450 isozyme induction potential of pemetrexed, because pemetrexed used as recommended (once every 21 days) would not be expected to cause any significant enzyme induction.
Due to the increased thrombotic risk in patients with cancer, the use of anticoagulation treatment is frequent. The high intraindividual variability of the coagulation status during diseases and the possibility of interaction between oral anticoagulants and anti-cancer chemotherapy require increased frequency of INR (International Normalised Ratio) monitoring, if it is decided to treat the patient with oral anticoagulants.
Concomitant use of pemetrexed with yellow fever vaccine is contraindicated due to the risk of fatal generalised vaccinale disease.
Concomitant use of pemetrexed with live attenuated vaccines (except yellow fever vaccine, which is not contraindicated) is not recommended due to the risk of systemic, possibly fatal, disease. The risk is increased in subjects who are already immunosuppressed by their underlying disease. Use an inactivated vaccine where it exists (poliomyelitis).
Cisplatin does not affect the pharmacokinetics of pemetrexed and the pharmacokinetics of total platinum are unaltered by pemetrexed.
Coadministration of oral folic acid or intramuscular vitamin B₁₂ does not affect the pharmacokinetics of pemetrexed.