Anagrelide

TITRATION: after one week the dose may be titrated on an individual basis to the lowest effective dose required to reduce and/or maintain the platelet count below 600 x 10^9/l, ideally between 150 x 10^9/l and 400 x 10^9/l. Increments must not exceed 0.5 mg/day in any one week. Doses of 10 mg/day have been used during clinical development. A fall in platelet count is typically seen within 14 to 21 days, and most patients achieve and maintain an adequate response at 1 to 3 mg/day. If the starting dose is greater than 1 mg/day, check platelet counts every two days during the first week and at least weekly thereafter until a stable maintenance dose is reached. Treatment should be initiated by a clinician experienced in the management of essential thrombocythaemia. ELDERLY: no different starting regimen or titration step is required. HEPATIC: patients with moderate or severe hepatic impairment should not be treated (also contraindicated); assess risks and benefits in mild impairment; not recommended if transaminases are greater than 5 times the upper limit of normal. DISCONTINUATION: avoid abrupt discontinuation — the platelet count rises within 4 days of stopping and returns to pre-treatment levels within 10 to 14 days, possibly rebounding above baseline, with a risk of fatal thrombotic complications such as cerebral infarction. MONITORING: full blood count, liver function (ALT, AST), renal function (creatinine, urea) and electrolytes (potassium, magnesium, calcium). CARDIOVASCULAR: a pre-treatment cardiovascular examination including baseline ECG and echocardiography is recommended for all patients, with regular monitoring during treatment; correct hypokalaemia or hypomagnesaemia before administration. PAEDIATRIC: safety and efficacy in children have not been established and experience is very limited — the UK SPC states that no recommendation on a posology can be made; anagrelide should be used with caution in this group, initiated only when there are signs of disease progression or thrombosis, with platelet targets set individually and discontinuation considered if there is no satisfactory response after approximately 3 months. For reference only, the US anagrelide prescribing information (openFDA, NOT UK labelling) states an adult starting dose of 0.5 mg four times daily or 1 mg twice daily, a paediatric starting dose of 0.5 mg daily (established in patients 7 years and older), a starting dose of 0.5 mg/day in moderate hepatic impairment, and that dosage should not exceed 10 mg/day or 2.5 mg in a single dose — verify against the UK SPC before use.