Interaction entre Cilostazol et Naproxène et ésoméprazole

Strong and moderate CYP3A4 and CYP2C19 inhibitors: Increase exposure to cilostazol.

Inhibitors of CYP3A4 or CYP2C19 Inhibitors of CYP3A4 Coadministration of strong (e.g., ketoconazole) and moderate (e.g., erythromycin, diltiazem and grapefruit juice) CYP3A4 inhibitors can increase exposure to cilostazol.

Inhibitors of CYP2C19 Coadministration with CYP2C19 inhibitors (e.g., omeprazole) increases systemic exposure of cilostazol active metabolites.

Reduce cilostazol dose to 50 mg twice daily when coadministered with strong or moderate inhibitors of CYP2C19 [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )].

Cilostazol Clinical Impact : Increased exposure of cilostazol and one of its active metabolites (3,4-­dihydro-cilostazol) when coadministered with omeprazole magnesium, the racemate of esomeprazole [see Clinical Pharmacology (12.3) ].

Intervention: Consider reducing the dose of cilostazol to 50 mg twice daily.

Co-morbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk.

Intervention: Monitor patients with concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see Warnings and Precautions ( 5.14 ) ].

Aspirin Clinical Impact: A pharmacodynamics (PD) study has demonstrated an interaction in which lower dose naproxen (220mg/day or 220mg twice daily) interfered with the antiplatelet effect of low-dose immediate-release aspirin, with the interaction most marked during the washout period of naproxen [see Clinical Pharmacology (12.2) ].