Anagrelideinteractions

Other PDE 3 inhibitors: Exacerbation of inotropic effects Aspirin and Drugs that Increase Bleeding Risk: Increased risk of bleeding with concomitant use

7.1 Drugs that

Prolong QT Avoid use of anagrelide in patients taking medications that may prolong QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, and pimozide).

7.2 PDE3 Inhibitors

Anagrelide is a phosphodiesterase 3 (PDE3) inhibitor. Avoid use of drug products with similar properties such as inotropes and other PDE3 inhibitors (e.g., cilostazol, milrinone).

7.3 Aspirin and

Drugs that Increase Bleeding Risk Co-administration of single-dose or repeat-dose anagrelide and aspirin showed greater ex vivo anti-platelet aggregation effects than administration of aspirin alone. Results from an observational study in patients with essential thrombocythemia suggest the rate of major hemorrhagic events (MHEs) in patients treated with anagrelide is higher than in those subjects treated with another cytoreductive treatment. The majority of the major hemorrhagic events occurred in patients who were also receiving concomitant anti-aggregatory treatment (primarily, aspirin). Therefore, the potential risks of the concomitant use of anagrelide with aspirin should be assessed, particularly in patients with a high-risk profile for hemorrhage, before treatment is initiated. Monitor patients for bleeding, particularly those receiving concomitant therapy with other drugs known to cause bleeding (e.g., anticoagulants, PDE3 inhibitors, NSAIDs, antiplatelet agents, selective serotonin reuptake inhibitors).

7.4 CYP450 Interactions CYP1A2 inhibitors:

Anagrelide and its active metabolite are primarily metabolized by CYP1A2. Drugs that inhibit CYP1A2 (e.g., fluvoxamine, ciprofloxacin) could increase the exposure of anagrelide. Monitor patients for cardiovascular events and titrate doses accordingly when CYP1A2 inhibitors are co-administered.

CYP1A2 inducers: CYP1A2 inducers could decrease the exposure of anagrelide. Patients taking concomitant CYP1A2 inducers (e.g., omeprazole) may need to have their dose titrated to compensate for the decrease in anagrelide exposure.

CYP1A2 substrates: Anagrelide demonstrates limited inhibitory activity towards CYP1A2 in vitro and may alter the exposure of concomitant CYP1A2 substrates (e.g., theophylline, fluvoxamine, ondansetron).