Anagrelide

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Agrylin (Orphan)
0.5 mg capsules
Approved indication: essential thrombocythaemia
Australian Medicines Handbook Section 7

Essential thrombocythaemia is an uncommon abnormality of the bone marrow. This clonal stem cell disorder results in the production of abnormal platelets and an increased platelet count. Patients are not only at risk of thrombosis, but also bleeding.1

Patients require treatment if they develop complications or if their platelet count exceeds 1000 x 109/L. While some patients require plateletpheresis, many patients are treated with hydroxyurea. This drug can have serious adverse effects so anagrelide will offer an alternative treatment.

Anagrelide was originally developed as an inhibitor of platelet aggregation, but was found to cause thrombocytopenia. It is thought to impair the maturation of megakaryocytes.

A clinical trial investigated anagrelide in 577 patients with conditions such as polycythaemia vera and chronic granulocytic leukaemia. The trial included 335 patients with essential thrombocythaemia, but only 262 were evaluable. After completing at least four weeks of treatment, 247 had a platelet count which had reduced by half or fallen below 600 x 109/L.2

Patients begin treatment with 0.5 mg four times a day or 1 mg twice a day for at least a week. The dose is adjusted to the lowest dose able to keep the platelet count under control. The platelet count should be measured every two days in the first week, then weekly until the maintenance dose is found. In clinical studies the mean duration of treatment was 65 weeks, but more than 20% of patients took anagrelide for two years.

The drug is rapidly absorbed. Although food reduces bioavailability the effect is not significant. Anagrelide has a half-life of 1.3 hours and is extensively metabolised. Most of the metabolites are excreted in the urine. Patients with liver or kidney disease must be monitored carefully as anagrelide may alter liver function and possibly cause renal failure.

Anagrelide causes vasodilatation. Patients may develop hypotension, palpitations, tachycardia and heart failure. These symptoms led to the withdrawal of some patients from the clinical trials. In total 15% of the patients withdrew. Other reasons for withdrawal included headache, diarrhoea and abdominal pain which are common adverse reactions to anagrelide.

Anaemia is common and thrombocytopenia can develop. In addition to full blood counts, renal and liver function should also be checked during treatment.

References

  1. Bentley MA, Taylor KM, Wright SJ. Essential thrombocythaemia. Med J Aust 1999;171:210-3.
  2. Anagrelide Study Group. Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Am J Med 1992;92:69-76.