Agrylin Drug Interactions

Limited pharmacokinetic and/or pharmacodynamic studies investigating possible interactions between anagrelide and other drugs have been conducted.
Drug interactions: effects of other substances on anagrelide: In vivo interaction studies in humans have demonstrated that digoxin and warfarin do not affect the pharmacokinetic properties of anagrelide.
CYP1A2 inhibitors: Anagrelide is primarily metabolised by CYP1A2. It is known that CYP1A2 is inhibited by several medicinal products, including fluvoxamine and omeprazole, and such medicinal products could theoretically adversely influence the clearance of anagrelide.
CYP1A2 inducers: CYP1A2 inducers (such as omeprazole) could decrease the exposure of anagrelide (see Pharmacology: Pharmacokinetics under Actions). The consequences on the safety and efficacy profile of anagrelide are not established. Therefore, clinical and biological monitoring is recommended in patients taking concomitant CYP1A2 inducers. If needed, anagrelide dose adjustment could be made.
Drug interactions: effects of anagrelide on other substances: Anagrelide demonstrates some limited inhibitory activity towards CYP1A2 which may present a theoretical potential for interaction with other co-administered medicinal products sharing that clearance mechanism, e.g. theophylline.
Anagrelide is an inhibitor of PDE III. The effects of medicinal products with similar properties such as the inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide.
In vivo interaction studies in humans have demonstrated that anagrelide does not affect the pharmacokinetic properties of digoxin or warfarin.
At the doses recommended for use in the treatment of essential thrombocythaemia, anagrelide may potentiate the effects of other medicinal products that inhibit or modify platelet function e.g. acetylsalicylic acid.
In two clinical interaction studies in healthy subjects, co-administration of single-dose anagrelide 1 mg and acetylsalicylic acid 900 mg or repeat-dose anagrelide 1 mg once daily and acetylsalicylic acid 75 mg once daily showed greater anti-platelet aggregation effects than administration of acetylsalicylic acid alone. In the repeat-dose study, there was a short-lived decrease in ex vivo collagen-induced platelet aggregation beyond the effects of acetylsalicylic acid alone for the first 2 hours after administration.
Co-administered anagrelide 1 mg and acetylsalicylic acid 900 mg single-doses had no effect on bleeding time, prothrombin time (PT) or activated partial thromboplastin time (aPTT). In some ET patients concomitantly treated by anagrelide and acetylsalicylic acid, major haemorrhages occurred. Therefore, the potential risks and benefits of concomitant use of anagrelide with acetylsalicylic acid should be assessed, particularly in patients with a high risk profile for haemorrhage, before treatment is commenced.
Anagrelide may cause intestinal disturbance in some patients and compromise the absorption of hormonal oral contraceptives.
Food interactions: Food delays the absorption of anagrelide, but does not significantly alter systemic exposure.
The effects of food on bioavailability are not considered clinically relevant to the use of anagrelide.