Thromboreductin Special Precautions

General: Anagrelide should only be used if the potential benefits of therapy outweigh the potential risks.
The therapy requires close clinical supervision of the patient including a complete blood count (haemoglobin, white blood cell and platelet counts) and tests regarding liver function (e.g. ALT and AST), renal function (serum creatinine and urea) and electrolytes (potassium, magnesium and calcium).
Treatment discontinuation and thrombotic risk: 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 anagrelide and will return to pre-treatment levels within 10 to 14 days, possibly rebounding above baseline values. Therefore, platelets should be monitored frequently (see Dosage & Administration).
Abrupt treatment discontinuation 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.
Cardiovascular effects: Serious cardiovascular adverse events, including cases of torsade de pointes, ventricular tachycardia, cardiomyopathy, cardiomegaly and congestive heart failure have been reported (see Adverse Reactions).
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 the QTc interval and hypokalaemia.
Close monitoring for an effect on the QTc interval is advisable.
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. in case of hepatic impairment or use with CYP1A2 inhibitors (see Interactions).
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 (PDE 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.
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.
Hepatic impairment (see Dosage & Administration and Contraindications): In patients with hepatic impairment, frequent liver function tests, especially at the beginning of the therapy, are necessary.
Renal impairment (see Dosage & Administration and Contraindications): In patients with renal impairment, frequent kidney function tests especially at the beginning of the therapy are necessary.
Thromboreductin contains lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and operate machinery have been performed. In clinical development, dizziness was a commonly reported side effect.
Patients are advised not to drive or operate machinery while taking Thromboreductin if dizziness is experienced.