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Indication
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Pharmacokinetic Interactions Strong CYP3A4 inducers may result in decreased exposure of tadalafil. tadalafil may increase exposure of BCRP substrates. Active Substances That Increase Osimertinib Plasma Concentrations In vitro studies have demonstrated that tadalafil undergoes phase I metabolism primarily via CYP3A4 and CYP3A5. In clinical pharmacokinetic studies, co-administration of 200 mg twice daily itraconazole (a strong CYP3A4 inhibitor) did not produce a clinically significant effect on tadalafil exposure (24% increase in area under the curve (AUC), 20% decrease in Cmax). Therefore, CYP3A4 inhibitors are unlikely to affect tadalafil exposure. No other enzymes that catalyze tadalafil have been identified. Active Substances That Decrease Osimertinib Plasma Concentrations In clinical pharmacokinetic studies, co-administration of rifampin (600 mg once daily for 21 days) decreased the steady-state AUC of tadalafil by 78%. Similarly, exposure to the metabolite AZ5104 was reduced, with AUC and Cmax decreasing by 82% and 78%, respectively. It is recommended that co-administration of this product with strong inducers of CYP3A4 (such as phenytoin, rifampicin, and carbamazepine) should be avoided. Moderate inducers of CYP3A4 (such as bosentan, efavirenz, etravirine, and modafinil) can also reduce exposure to this product and should therefore be used with caution and avoided if possible. When co-administration of osimertinib with strong inducers of CYP3A is unavoidable, the dose of osimertinib needs to be increased to 160 mg per day. Three weeks after discontinuation of strong inducers of CYP3A4, the dose of osimertinib can be restored to 80 mg per day. This product is contraindicated for co-administration with St. John's wort (see [Contraindications]). Effects of acid-suppressing drugs on osimertinib In clinical pharmacokinetic studies, co-administration of omeprazole did not have a clinically relevant effect on the exposure of this product. This product can be used in combination with drugs that change the intragastric pH without any restrictions. Other active substances whose plasma concentration may be altered after taking osimertinib Based on the results of in vitro studies, this product is a competitive inhibitor of the BCRP transporter. In clinical PK studies, the AUC and Cmax of rosuvastatin (a sensitive BCRP substrate) increased by 35% and 72%, respectively, after the product was co-administered with this product. When taking this product, if the patient is taking drugs that rely on BCRP for distribution and have a narrow therapeutic index, they should be closely monitored to promptly detect changes in tolerance due to increased exposure to the combined drug. (See [Pharmacokinetics]). In clinical PK studies, the AUC and Cmax of simvastatin (a sensitive CYP3A4 substrate) increased by 9% and 23%, respectively, after the product was co-administered with this product. This change is small and therefore unlikely to be clinically significant. This product is unlikely to have PK interactions with CYP3A4 substrates. In addition to CYP3A4, we have not studied the interaction of other enzymes regulated by the pregnane X receptor (PXR). The risk of decreased exposure to hormonal contraceptives cannot be excluded after co-administration of this product. |
