Agrylin Dosage/Direction for Use

Treatment with Agrylin capsules should be initiated by a clinician with experience in the management of essential thrombocythaemia.
The recommended starting dosage of anagrelide is 1 mg/day, which should be administered orally, in two divided doses (0.5 mg/dose).
The starting dose should be maintained for at least one week. After one week the dosage may be titrated, on an individual basis, to achieve the lowest effective dosage required to reduce and/or maintain a platelet count below 600 x 10⁹/L and ideally at levels between 150 x 10⁹/L and 400 x 10⁹/L. The dosage increment must not exceed 0.5 mg/day in any one week and the maximum single dose should not exceed 2.5 mg (see Overdosage). During clinical development dosages of 10 mg/day have been used.
The effects of treatment with anagrelide must be monitored on a regular basis (see Precautions). If the starting dose is >1 mg/day platelet counts should be performed every two days during the first week of treatment and at least weekly thereafter until a stable maintenance dose is reached.
Typically, a fall in the platelet count will be observed within 14 to 21 days of starting treatment and in most patients an adequate therapeutic response will be observed and maintained at a dosage of 1 to 3 mg/day (for further information on the clinical effects refer to Pharmacology: Pharmacodynamics under Actions).
Elderly: The observed pharmacokinetic differences between elderly and young patients with ET (see Pharmacology: Pharmacokinetics under Actions) do not warrant using a different starting regimen or different dose titration step to achieve an individual patient-optimised anagrelide regimen.
During the clinical development approximately 50% of the patients treated with anagrelide were over 60 years of age and no age specific alterations in dosage were required in these patients. However, as expected, patients in this age group had twice the incidence of serious adverse events (mainly cardiac).
Renal impairment: Currently, there are no specific pharmacokinetic data for this patient population and the potential risks and benefits of anagrelide therapy in a patient with impairment of renal function should be assessed before treatment is commenced.
Hepatic Impairment: Currently, there are no specific pharmacokinetic data for this patient population. However, hepatic metabolism represents the major route of drug clearance and liver function may therefore be expected to influence this process. Therefore it is recommended that patients with moderate or severe hepatic impairment are not treated with anagrelide. The potential risks and benefits of anagrelide therapy in a patient with mild impairment of hepatic function should be assessed before treatment is commenced (see Contraindications and Precautions).
Paediatric patients: The experience in children is limited; anagrelide should be used in this patient group with caution (see Pharmacology: Pharmacodynamics and Pharmacokinetics under Actions).