Agrylin Special Precautions

Hepatic impairment: (See Dosage & Administration and Contraindications) 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).
Renal impairment: (See Dosage & Administration and Contraindications) The potential risks and benefits of anagrelide therapy in a patient with impairment of renal function should be assessed before treatment is commenced.
Monitoring: Therapy requires close clinical supervision of the patient which will include a full blood count (haemoglobin and white blood cell and platelet counts), renal function (serum creatinine and urea) tests and electrolytes (potassium, magnesium and calcium). As cases of hepatitis have been reported from postmarketing surveillance, it is recommended that liver function tests (ALT and AST) are performed before anagrelide treatment is initiated and at regular intervals thereafter.
Thrombotic Risk: Abrupt treatment discontinuation or substantial reduction of anagrelide's dose should be avoided due to the risk of sudden increase in platelet counts, which may lead to potentially fatal thrombotic complications, such as cerebral infarction. Patients should be advised how to recognize early signs and symptoms suggestive of thrombotic complications, such as cerebral infarction, and if symptoms occur to seek medical assistance.
Treatment discontinuation: In the event of dosage interruption or treatment withdrawal, the rebound in platelet count is variable, but the platelet count will start to increase within 4 days of stopping treatment with Agrylin capsules and will return to pre-treatment levels within 10 to 14 days. Possibly rebounding above baseline values. Therefore platelets should be monitored frequently.
Cardiovascular: Cases of cardiomegaly and congestive heart failure have been reported (see Adverse Reactions). Anagrelide should be used with caution in patients of any age with known or suspected heart disease, and only if the potential benefits of therapy outweigh the potential risks. Anagrelide is an inhibitor of cyclic AMP phosphodiesterase III and because of its positive inotropic and chronotropic effects, a pre-treatment cardiovascular examination (including further investigation such as echocardiography, electrocardiogram) is recommended for all patients. Patients should be monitored during treatment for evidence of cardiovascular effects that may require further cardiovascular examination and investigation.
Anagrelide has been shown to increase the heart rate, resulting in an apparent increase in QTc interval of the electrocardiogram in healthy volunteers. The clinical impact of this effect is unknown (see Pharmacology: Pharmacodynamics under Actions).
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 (C_max) of anagrelide or its active metabolite, 3-hydroxy-anagrelide, e.g. hepatic impairment or use with CYP1A2 inhibitors (see Interactions).
Pulmonary hypertension: Cases of pulmonary hypertension have been reported in patients treated with anagrelide. Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to initiating and during anagrelide therapy.
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. The risks and benefits of the concomitant use of anagrelide with acetylsalicylic acid should be assessed, particularly in patients with a high risk profile for haemorrhage, before treatment is commenced.
Excipients: Agrylin contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: No specific studies on the effects on the ability to drive and use machines have been performed with Agrylin.
In clinical development, dizziness was commonly reported.
Patients are advised not to drive or operate machinery while taking Agrylin if dizziness is experienced.
Use in Children: (See Dosage & Administration and Pharmacology: Pharmacokinetics under Actions) Limited data are available on the use of anagrelide in the paediatric population and anagrelide should be used in this patient group with caution.