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Drug interactions of Anagrelide

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)

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)

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).

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).

FDA，2021.10