Brilinta Drug Interactions

Drug-Drug Interactions: Effects of Other Drugs on Ticagrelor (BRILINTA): Medicinal Products metabolised by CYP3A4: Ketoconazole (Strong CYP3A4 Inhibitors): Co-administration of ketoconazole with Ticagrelor increased Ticagrelor C_max and AUC equal to 2.4-fold and 7.3-fold, respectively. The C_max and AUC of the active metabolite were reduced by 89% and 56%, respectively. Other strong inhibitors of CYP3A4 (clarithromycin, nefazodone, ritonavir, and atazanavir) would be expected to have similar effects and should not be given concomitantly with Ticagrelor (BRILINTA) (see Precautions).
Diltiazem (Moderate CYP3A4 inhibitors): Co-administration of Ticagrelor and diltiazem increased the C_max of Ticagrelor by 69% and AUC by 174%, and decreased the active metabolite C_max by 38% and AUC was unchanged. There was no effect of Ticagrelor on diltiazem plasma levels. Other moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, erythromycin, fluconazole, and verapamil) can as well be co-administered with Ticagrelor (BRILINTA).
Rifampin and Other CYP3A Inducers: Co-administration of rifampin with Ticagrelor decreased Ticagrelor C_max and AUC by 73% and 86%, respectively. The C_max of the active metabolite was unchanged and the AUC was decreased by 46%, respectively. Other CYP3A4 inducers (e.g. phenytoin, carbamazepine, and phenobarbital) would be expected to decrease the exposure to Ticagrelor as well and may result in reduced efficacy of Ticagrelor (BRILINTA).
Cyclosporine (P-gP and CYP3A inhibitor): Co-administration of cyclosporine (600 mg) with ticagrelor increased ticagrelor C_max and AUC equal to 2.3-fold and 2.8-fold, respectively. The AUC of the active metabolite was increased by 32% and Cmax was decreased by 15% in the presence of cyclosporine. There was no effect of ticagrelor on cyclosporine blood levels.
Others: Clinical pharmacology interaction studies showed that co-administration of Ticagrelor with heparin, enoxaparin, and ASA did not have any effect on Ticagrelor or the active metabolite plasma levels. Co-administration of Ticagrelor and heparin had no effect on heparin based on activated partial thromboplastin time (aPTT) and activated coagulation time (ACT) assays. Co-administration of Ticagrelor and enoxaparin had no effect on enoxaparin based on factor Xa assay.
Delayed and decreased exposure to oral P2Y₁₂ inhibitors, including ticagrelor and its active metabolite, has been reported in patients treated with morphine (approximately 35% reduction in ticagrelor). This interaction may be related to reduced gastrointestinal motility, and therefore apply to other opioids. The clinical relevance is unknown.
Effects of Ticagrelor (BRILINTA) on Other Drugs: Medicinal Products metabolised by CYP3A4: Simvastatin: Co-administration of Ticagrelor with simvastatin increased simvastatin C_max by 81% and AUC by 56% and increased simvastatin acid C_max by 64% and AUC by 52% with some individual increases equal to 2 to 3-fold. Consideration of the clinical significance should be given to the magnitude and range of changes on the exposure to patients requiring greater than 40 mg of simvastatin. There was no effect of simvastatin on Ticagrelor plasma levels. Ticagrelor (BRILINTA) may have similar effect on lovastatin, but is not expected to have a clinically meaningful effect on other statins.
Atorvastatin: Co-administration of atorvastatin and Ticagrelor increased atorvastatin acid C_max by 23% and AUC by 36%. Similar increases in AUC and C_max were observed for all atorvastatin acid metabolites. These increases are not considered clinically significant.
Medicinal products metabolised by CYP2C9: Tolbutamide: Co-administration of Ticagrelor with tolbutamide resulted in no change in the plasma levels of either drug, which suggest that Ticagrelor is not a CYP2C9 inhibitor and unlikely to alter the CYP2C9 mediated metabolism of drugs like warfarin and tolbutamide.
Oral Contraceptives: Co-administration of Ticagrelor and levonorgestrel and ethinyl estradiol increased ethinyl estradiol exposure by approximately 20% but did not alter the PK of levonorgestrel. No clinically relevant effect on oral contraceptive efficacy is expected when levonorgestrel and ethinyl estradiol are co-administered with Ticagrelor (BRILINTA).
Digoxin (P-gP substrate): Concomitant administration of Ticagrelor increased the digoxin C_max by 75% and AUC by 28%. Therefore, appropriate clinical and/or laboratory monitoring is recommended when giving narrow therapeutic index P-gp dependent drugs like digoxin concomitantly with Ticagrelor (BRILINTA).
Other Concomitant Therapy: In clinical studies, Ticagrelor (BRILINTA) was commonly administered with ASA, heparin, low molecular weight heparin, intravenous GpIIb/IIIa inhibitors, proton pump inhibitors, statins, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers as needed for concomitant conditions. These studies did not produce any evidence of clinically significant adverse interactions.