Anagrelide is an active substance from the antineoplastic group. The drug is available in Germany in the form of hard capsules under the trade name Xagrid and as generics. Anagrelide is used to treat essential thrombocythemia.
What is anagrelide?
Anagrelide is used to treat essential thrombocythemia. Anagrelide is used to treat essential thrombocytosis, which is characterized by an increased number of platelets produced in the bone marrow in the blood. Anagrelide is also recommended as a second-line therapy for so-called high-risk patients who did not tolerate or respond well enough to previous treatment. The drug anagrelide was approved by the European Medicines Agency – or EMEA for short – at the end of 2004 as a secondary therapy for this group of patients who are intolerant to or do not respond to the previous primary therapy. Anagrelide was originally developed as an antiplatelet agent. However, the agent inhibits megakaryocyte maturation in parallel as well.
Pharmacologic Action
The pharmacologic effects of anagrelide on the body and organs have not yet been elucidated. Initial research led to the assumption that anagrelide administration caused platelet aggregation inhibition. This is the effect of inhibiting the clumping of blood platelets, which promotes the formation of blood clots – thrombi. However, further studies showed that anagrelide does not exert an antiplatelet effect. Nevertheless, it very rapidly reduces the amount of platelets in the blood. It is not known why. What is certain, however, is that anagrelide acts well as an inhibitor of type 3 cAMP phosphodiesterase. Thus, the answer to anagrelin’s mode of action is probably to be sought here. The drug appears to insert itself into the postmitotic phase in megakaryocyte development, affecting their maturation and size as well as chromosome number. Inhibition of phosphodiesterase III increases platelet cyclic adenosine monophosphate (cAMP) levels in the blood. High-dose anagrelide also inhibits this aggregation. Anagrelide exhibits platelet-selective activity and therefore does not affect white and red blood cell formation. Clinical trials involving more than 4000 patients suffering from myeloproliferative disorders showed that they responded to anagrelide therapy within 4 to 12 weeks.
Medical Application and Use
Anagrelide is used for the treatment of thrombocytosis. Patients with thrombocytoses suffer from myeloproliferative disorders such as.
- Essential thrombocythemia (ET).
- Polycythaemia vera (PV)
- Chronic myeloid leukemia (CML)
- Osteomyelofibrosis (OMF)
In thrombocytosis, there is an increased number of platelets produced in the bone marrow and released into the bloodstream. These platelets, also known as thrombocytes, in excess easily lead to hemorrhagic and thrombotic diseases such as transient ischemic attacks (TIA), stroke or thrombosis of smaller blood vessels. In rare cases, acute leukemia may develop. When thrombocytosis is diagnosed, many of those affected, who are usually over 50 years of age, do not yet have any subjective symptoms. Nevertheless, because of the existing risks, timely medical countermeasures should be taken. The recommended starting dose for anagrelide is 1 mg per day, divided into two doses. The capsules can be taken either with a meal or fasting. After one week, individual dose adjustment is made, with a maximum single dose of 2.5 mg. After discontinuation of anagrelide, the platelet count returns to baseline in 10 to 14 days. Close monitoring of liver and renal laboratory values must be performed during anagrelide therapy.
Risks and Side Effects
When taking anagrelide, adverse side effects may include:
- Abdominal pain
- Nausea
- Flatulence
- Diarrhea
- Dizziness
- Headache
- Palpitations
- Tachycardia
- Weakness
- Edema
After the launch of anagrelide, serious cardiovascular side effects could be observed during its use.These also affected patients without suspected cardiac disease or normal findings in cardiovascular examinations performed prior to initiation of therapy with anagrelide. Therefore, anagrelide is only considered as second-line therapy in high-risk patients. Anagrelide is contraindicated in patients with increased sensitivity to the active ingredient, moderate to severe liver impairment, and renal insufficiency. Pregnant and breastfeeding women are also excluded from anagrelide therapy. Anagrelide interacts with the following medications:
- Antiplatelet agents
- Phosphodiesterase inhibitors
- Acetylsalicylic acid
- Sucralfate
