Anagrelide: a novel agent for the treatment of myeloproliferative disorders

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Abstract
Anagrelide hydrochloride (Agrylin, Roberts Pharmaceutical Corp.) is an oral imidazoquinazoline agent that has been shown to reduce elevated platelet counts and the risk of thrombosis in patients with thrombocythaemia in various myeloproliferative disorders (MPD). It is currently approved by the FDA as oral treatment for essential thrombocythaemia (ET) and thrombocythaemia associated with polycythaemia vera (PV). Anagrelide selectively suppresses bone marrow megakaryocytes by interfering with the maturation process and decreasing platelet production without affecting the erythroid and myeloid progenitor cells. Other medications indicated for the treatment of thrombocythaemia, including interferon alpha (IFN-alpha), alkylating agents and hydroxyurea, suppress all cell lines. Anagrelide is known to inhibit platelet cyclic adenosine monophosphate (cAMP) phosphodiesterase at concentrations that exceed those achieved at doses used to treat ET. Anagrelide is extensively metabolised in the liver and its metabolites are primarily excreted in the urine. Adverse effects associated with the use of anagrelide are primarily caused by the drugs' direct vasodilating and positive inotropic effects. These include headache, hypotension and diarrhoea. It has also been known to cause fluid retention, tachycardia, nausea, abdominal pain and arrhythmias. The starting dose of anagrelide ranges from 0.5 mg q.i.d. to 1 mg b.i.d. with a maximum dose of 2.5 mg q.i.d. Adequate responses have been maintained with a median dose of 2-2.5 mg/day. Platelet counts begin to decrease in 7-10 days, however, they return to pre-treatment levels within 4-8 days if therapy is stopped. Anagrelide 2 mg/day for one year costs approximately US$6439, and treatment must continue indefinitely [1].