Brilinta Drug Interactions

Effects of other drugs: Ticagrelor is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5. Ticagrelor is also a p-glycoprotein (P-gp) substrate.
CYP3A inhibitors: Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) (see Warnings, Precautions and Pharmacology under Actions).
CYP3A inducers: Avoid use with potent inducers of CYP3A (e.g., rifampin, phenytoin, carbamazepine and phenobarbital) (see Warnings, Precautions and Pharmacology under Actions).
Aspirin: Use of BRILINTA with aspirin maintenance doses above 100 mg reduced the effectiveness of BRILINTA (see Warnings, Precautions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Effect of BRILINTA on other drugs: Ticagrelor is an inhibitor of CYP3A4/5 and the P-glycoprotein transporter.
Simvastatin, lovastatin: BRILINTA will result in higher serum concentrations of simvastatin and lovastatin because these drugs are metabolized by CYP3A4. Avoid simvastatin and lovastatin doses greater than 40 mg (see Pharmacology under Actions).
Digoxin: Digoxin: Because of inhibition of the P-glycoprotein transporter, monitor digoxin levels with initiation of or any change in BRILINTA therapy (see Pharmacology under Actions).
Other Concomitant Therapy: BRILINTA can be administered with unfractionated or low-molecular-weight heparin, GPIIb/IIIa inhibitors, proton-pump inhibitors, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers.
Cyclosporine (Pgp and CYP3A inhibitor): Coadministration of cyclosporine (600 mg) with ticagrelor increased ticagrelor Cmax 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. No data are available on concomitant use of ticagrelor with other active substances that also are potent Pgp inhibitors and moderate CYP3A4 inhibitors (e.g. verapamil, quinidine) that also may increase ticagrelor exposure. If the association cannot be avoided, their concomitant use should be made with caution.
Oral contraceptives: Coadministration of ticagrelor and levonorgestrel and ethinyl estradiol increased ethinyl estradiol exposure approximately 20% but did not alter the pharmacokinetics of levonorgestrel. No clinically relevant effect on oral contraceptive efficacy is expected when levonorgestrel and ethinyl estradiol are coadministered with ticagrelor.
Medicinal products known to induce bradycardia: Due to observations of mostly asymptomatic ventricular pauses and bradycardia, caution should be exercised when administering ticagrelor concomitantly with medicinal products known to induce bradycardia. However, no evidence of clinically significant adverse reactions was observed in the PLATO trial after concomitant administration with one or more medicinal products known to induce bradycardia (e.g. 96% beta blockers, 33% calcium channel blockers diltiazem and verapamil, and 4% digoxin).
Others: Clinical pharmacology interaction studies showed that coadministration of ticagrelor with heparin, enoxaparin and ASA or desmopressin did not have any effect on the pharmacokinetics of ticagrelor or the active metabolite or on ADP induced platelet aggregation compared with ticagrelor alone. If clinically indicated, medicinal products that alter haemostasis should be used with caution in combination with ticagrelor. A 2 fold increase of ticagrelor exposure was observed after daily consumption of large quantities of grapefruit juice (3 x 200 ml). This magnitude of increased exposure is not expected to be clinically relevant to most patients.
A delayed and decreased exposure to oral P2Y12 inhibitors, including ticagrelor and its active metabolite, has been observed in patients with ACS treated with morphine (35% reduction in ticagrelor exposure). This interaction may be related to reduced gastrointestinal motility and apply to other opioids. The clinical relevance is unknown, but data indicate the potential for reduced ticagrelor efficacy in patients co-administered ticagrelor and morphine. In patients with ACS, in whom morphine cannot be withheld and fast P2Y12 inhibition is deemed crucial, the use of a parenteral P2Y12 inhibitor may be considered.