Difference between revisions of "Anagrelide"

Latest revision as of 10:09, 20 September 2010

Anagrelide (Agrylin/Xagrid, Shire) is a drug used for the treatment of essential thrombocytosis (ET; essential thrombocythemia). It also has been used in the treatment of chronic myeloid leukemia. ^[1]

Mechanism

It works by inhibiting the maturation of platelets from megakaryocytes.^[2] The exact mechanism of action is unclear, although it is known to be a phosphodiesterase inhibitor.^[3] It is a potent (IC₅₀ = 36nM) inhibitor of phosphodiesterase-II.^{[citation needed]}

Uses

According to a 2005 Medical Research Council randomized trial, the combination of hydroxyurea with aspirin is superior to the combination of anagrelide and aspirin for the initial management of ET. The hydroxyurea arm had a lower likelihood of myelofibrosis, arterial thrombosis, and bleeding, but it had a slightly higher rate of venous thrombosis.^[4]

Side-effects

Common side effects are headache, diarrhea, unusual weakness/fatigue, hair loss, nausea and dizziness.

The same MRC trial mentioned above also analyzed the effects of anagrelide on bone marrow fibrosis, a common feature in patients with myelofibrosis. The use of anagrelide was associated with a rapid increase in the degree of reticulin deposition (the mechanism by which fibrosis occurs), when compared to those in whom hydroxyurea was used. Patients with myeloproliferative conditions are known to have a very slow and somewhat variable course of marrow fibrosis increase. This trend may be accelerated by anagrelide. Interestingly, this increase in fibrosis appeared to be linked to a drop in hemoglobin as it progressed. Fortunately, stopping the drug (and switching patients to hydroxyurea) appeared to reverse the degree of marrow fibrosis. Thus, patients on anagrelide may need to be monitored on a periodic basis for marrow reticulin scores, especially if anemia develops, or becomes more pronounced if present initially. ^[5]

Less common side effects include: congestive heart failure, myocardial infarction, cardiomyopathy, cardiomegaly, complete heart block, atrial fibrillation, cerebrovascular accident, pericarditis, pulmonary infiltrates, pulmonary fibrosis, pulmonary hypertension, pancreatitis, gastric/duodenal ulceration, renal impairment/failure and seizure.

Due to these issues, anagrelide should not generally be considered for first line therapy in ET.

References

1. ↑ Voglová J, Maisnar V, Beránek M, Chrobák L (2006). "[Combination of imatinib and anagrelide in treatment of chronic myeloid leukemia in blastic phase]". Vnitr̆ní lékar̆ství (in Czech). 52 (9): 819–22. PMID 17091608. CS1 maint: Multiple names: authors list (link) CS1 maint: Unrecognized language (link)
2. ↑ Petrides PE (2006). "Anagrelide: what was new in 2004 and 2005?". Semin. Thromb. Hemost. 32 (4 Pt 2): 399–408. doi:10.1055/s-2006-942760. PMID 16810615. 
3. ↑ PMID 3027338
4. ↑ Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR; United Kingdom Medical Research Council Primary Thrombocythemia 1 Study. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005;353:33-45. PMID 16000354.
5. ↑ http://www.ncbi.nlm.nih.gov/pubmed/19364963?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1, J Clin Oncol. 2009 Jun 20;27(18):2991-9. Reticulin accumulation in essential thrombocythemia: prognostic significance and relationship to therapy. Campbell PJ, Bareford D, Erber WN, Wilkins BS, Wright P, Buck G, Wheatley K, Harrison CN, Green AR.

External links

• Shire Pharmaceuticals Agrylin/Xagrid website for international visitors
• Shire Pharmaceuticals Xagrid website for UK visitors

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