Anagrelide

• 6,7- dichloro-1 ,5- dihydroimidazo [2,1 b] quinazolin- 2-one
• Latin: Anagrelidum

• 68475-42-3
• 58579-51-4 (hydrochloride)

L01XX35

Cytostatic

> 280 ° C ( as hydrochloride)

Template: Infobox chemical / molecular formula search available

Anagrelide (trade name Xagrid ®, manufacturer Shire Pharmaceuticals ) is a drug from the group of imidazolidine compounds. Anagrelide reduces the number of platelets produced by the bone marrow and reduced in this way the number of circulating platelets in the blood back to normal levels. It is used in the treatment of thrombocytosis, that occur in patients with myeloproliferative diseases such as essential thrombocythemia (ET), Polycythemia Vera ( PV), chronic myeloid leukemia (CML) or myelofibrosis (OMF ).

Mechanism of action

After the drug was originally an inhibitory effect on platelet aggregation ( inhibition of platelet aggregation ) was attributed, clinical studies have shown that the substance has no effect on platelet function, but leads to a rapid drop in the platelet count in the blood. The exact mechanism of action is still unclear. However, it is known that anagrelide inhibits cAMP phosphodiesterase type 3. Based on studies in cell cultures is discussed that the substance acts in the precursor cells of platelets ( megakaryocytes ), by slowing the ripening and their size and ploidy reduced.

Side effects

• Common: headache, dizziness, fatigue, strong heartbeat, nausea, diarrhea, anemia

The therapy requires clinical monitoring of the patient regarding blood count, kidney and liver function. After the launch of serious cardiovascular side effects were observed in patients without evidence of heart disease, with normal findings at inquiries carried out before treatment cardiovascular examinations were observed. Anagrelide is used carefully in patients of any age with known or suspected heart disease and provided at-risk patients as second-line therapy.

Compared anagrelide versus hydroxyurea

A 2005 "New England Journal of Medicine " published study suggests, however, suggest that anagrelide of the reference substance hydroxyurea is inferior: About 800 people with essential thrombocythemia, have failed due to high platelet count (over 1 million / ul) and other criteria a high risk consisted of vascular complications, were next to low-dose acetylsalicylic acid (ASA ) of 75-100 mg anagrelide or hydroxyurea either.

Only 9 % of patients in the anagrelide group 14%, in the hydroxyurea group, however, suffered an arterial or venous thrombosis or a serious bleeding - After an observation period of more than 3 years had - with a comparable reduction in platelet count. The discontinuation rate in the anagrelide group was also higher. Under anagrelide, a transformation was also significantly more often occurred in a myelofibrosis. The above-mentioned study, however, has been criticized due to methodological inaccuracies and the results of other ongoing studies should be awaited.

Trade names

Agrylin ( U.S., CDN), Thromboreductin (A), Xagrid (D, CH)