General Information

Agrylin (anagrelide) is a platelet reducing agent.

Agrylin is specifically indicated for the treatment of thrombocythemia, secondary to myeloproliferative neoplasms, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events.

Agrylin is supplied as capsules for oral administration. The recommended starting dose for adults is 0.5 mg four times a day or 1 mg twice a day. The starting dose for pediatric patients is 0.5 mg per day. Maintain the starting dose for at least one week and then titrate to maintain target platelet counts. Do not exceed a dose increment of 0.5 mg/day in any one week. Do not exceed 10 mg/day or 2.5 mg in a single dose. For patients with moderate hepatic impairment, start with 0.5 mg per day.

Mechanism of Action

Agrylin (anagrelide) is a platelet reducing agent. The precise mechanism by which anagrelide reduces blood platelet count is unknown. In cell culture studies, anagrelide suppressed expression of transcription factors including GATA-1 and FOG-1 required for megakaryocytopoiesis, ultimately leading to reduced platelet production.

Side Effects

Adverse effects associated with the use of Agrylin may include, but are not limited to, the following:

headache

palpitations

diarrhea

asthenia

edema

nausea

abdominal pain

dizziness

pain

dyspnea

cough,

flatulence

vomiting

fever

peripheral edema

rash

chest pain

anorexia

tachycardia

malaise

paresthesia

back pain

pruritus

dyspepsia

Clinical Trial Results

The FDA approval of Agrylin in adults was based on three clinical trials in a total of 942 patients with myeloproliferative neoplasms including 551 patients with Essential Thrombocythemia (ET), 117 patients with Polycythemia Vera (PV), 178 patients with Chronic Myelogenous Leukemia (CML), and 96 patients with other myeloproliferative neoplasms (OMPN). Patients were enrolled in clinical trials if their platelet count was ≥900,000/µL on two occasions or ≥650,000/µL on two occasions with documentation of symptoms associated with thrombocythemia. The mean duration of Agrylin therapy for ET, PV, CML, and OMPN patients was 65, 67, 40, and 44 weeks, respectively; 23% of patients received treatment for 2 years. Patients were treated with Agrylin starting at doses of 0.5-2.0 mg every 6 hours. The dose was increased if the platelet count was still high, but to no more than 12 mg each day. Efficacy was defined as reduction of platelet count to or near physiologic levels (150,000-400,000/µL). The trial demonstrated efficacy by meeting the criteria for “responders”, defined as the reduction in platelets for at least 4 weeks to ≤600,000/µL, or by at least 50% from baseline value.