Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hepatic impairment
The potential risks and benefits of anagrelide therapy in a patient with mild impairment of hepatic function should be assessed before treatment is commenced. It is not recommended in patients with elevated transaminases (> 5 times the upper limit of normal) (see sections 4.2 and 4.3).

Renal impairment
The potential risks and benefits of anagrelide therapy in a patient with impairment of renal function should be assessed before treatment is commenced (see sections 4.2 and 4.3).

Monitoring
Therapy requires close clinical supervision of the patient which will include a full blood count (haemoglobin and white blood cell and platelet counts), assessment of liver function (ALT and AST), renal function (serum creatinine and urea) and electrolytes (potassium, magnesium and calcium).
Platelets
The platelet count will increase within 4 days of stopping treatment with Agrylin capsules and will return to pre-treatment levels within 10 to 14 days.

Cardiovascular
Serious cardiovascular adverse events including cases of torsade de pointes, ventricular tachycardia, cardiomyopathy, cardiomegaly and congestive heart failure have been reported (see section 4.8).

Caution should be taken when using anagrelide in patients with known risk factors for prolongation of the QT interval, such as congenital long QT syndrome, a known history of acquired QTc prolongation, medicinal products that can prolong QTc interval and hypokalaemia.

Care should also be taken in populations that may have a higher maximum plasma concentration (Cmax) of anagrelide or its active metabolite, 3-hydroxy-anagrelide, e.g. hepatic impairment or use with CYP1A2 inhibitors (see section 4.5).

Close monitoring for an effect on the QTc interval is advisable.

A pre-treatment cardiovascular examination, including a baseline ECG and an echocardiography is recommended prior to initiating therapy with anagrelide. Patients should be monitored during treatment for evidence of cardiovascular effects that may require further cardiovascular examination and investigation. Hypokalaemia or hypomagnesaemia must be corrected prior to anagrelide administration and should be monitored periodically during therapy.

Anagrelide is an inhibitor of cyclic AMP phosphodiesterase III and because of its positive inotropic and chronotropic effects, anagrelide should be used with caution in patients of any age with known or suspected heart disease. Moreover, serious cardiovascular adverse events have also occurred in patients without suspected heart disease and with normal pre-treatment cardiovascular examination.

Anagrelide should only be used if the potential benefits of therapy outweigh the potential risks.

Paediatric population
Limited data are available on the use of anagrelide in the paediatric population and anagrelide should be used in this patient group with caution (see sections 5.1 and 5.2).

Clinically relevant interactions
Anagrelide is an inhibitor of cyclic AMP phosphodiesterase III (PDE III). Concomitant use of anagrelide with other PDE III inhibitors such as milrinone, amrinone, enoximone, olprinone and cilostazol is not recommended.
Agrylin contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Effects on Driving

4.7   Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.

In clinical development, dizziness was commonly reported. Patients are advised not to drive or operate machinery while taking Agrylin if dizziness is experienced.