cytic metaplasia in bone marrow
• Splenomegaly
• Moderate to severe normo-chromic normocytic anemia
• White cell count may be variable; (80,000-100,000/µL)
• Increased platelet count
• Variable red cell mass; teardrop poikilocytes
• Normal to high leukocyte alkaline phosphatase• Absence of Philadelphia chromosome
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 anagrelide therapy for ET, PV, CML, and OMPD patients was 65, 67, 40, and 44 weeks, respectively; 23% of patients received treatment for 2 years. Patients were treated with anagrelide 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 criteria for defining subjects as “responders” were reduction in platelets for at least 4 weeks to ≤600,000/µL, or by at least 50% from baseline value. Subjects treated for less than 4 weeks were not considered eva luable. The results are depicted graphically below:
*x 103 /μL
Nine hundred and forty-two subjects with myeloproliferative disorders were enrolled in three research studies. Of these, 923 had platelet counts over the duration of the studies.
AGRYLIN ® was effective in phlebotomized patients as well as in patients treated with other concomitant therapies including hydroxyurea, aspirin, interferon, radioactive phosphorus, and alkylating agents.
INDICATIONS AND USAGEAGRYLIN ® Capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events (see CLINICAL STUDIES, DOSAGE AND ADMINISTRATION).
CONTRAINDICATIONSAnagrelide is contraindicated in patients with severe hepatic impairment. Exposure to anagrelide is increased 8-fold in patients with moderate hepatic impairment (see CLINICAL PHARMACOLOGY). Use of anagrelide in patients with severe hepatic impairment has not been studied (see also WARNINGS: Hepatic).
WARNINGSCardiovascular
Torsades de pointes and ventricular tachycardia have been reported with anagrelide treatment. Obtain a pre-treatment cardiovascular examination, including an ECG in all patients. During treatment with Agrylin, monitor patients for cardiovascular effects and eva luate as necessary.
Anagrelide is a phosphodiesterase 3 (PDE3) inhibitor and may cause vasodilation, tachycardia, palpitations, and congestive heart failure. Other drugs that inhibit PDE3 have caused decreased survival when compared with placebo in patients with Class III-IV congestive heart failure. In patients with cardiac disease, use Agrylin only when the benefits outweigh the risks.
Hepatic
Exposure to anagrelide is increased 8-fold in patients with moderate hepatic impairment (see CLINICAL PHARMACOLOGY). Use of anagrelide in patients with severe hepatic impairment has not been studied. The potential risks and benefits of anagrelide therapy in a patient with mild and moderate impairment of hepatic function should be ass |
