25 mg and 50 mg tablets
Approved indication: idiopathic thrombocytopenic purpura
Australian Medicines Handbook Appendix A
Chronic idiopathic thrombocytopenic purpura is an immune condition caused by autoantibodies which bind to platelets. This leads to increased destruction of platelets, putting patients at risk of bleeding. The condition tends to have episodes of relapse and remission. If it cannot be controlled by corticosteroids, immunoglobulins or splenectomy, a drug such as romiplostim can be given to stimulate platelet production.
Like romiplostim, eltrombopag increases platelet production by interacting with the thrombopoietin receptor. Whereas romiplostim is a peptide which has to be injected, eltrombopag is a small non-peptide molecule which can be given orally. It should not be taken within four hours of antacids, dairy products or mineral supplements as these reduce absorption. Higher concentrations are reached in East Asian patients so a lower starting dose (25 mg) is recommended. Most of the dose is metabolised and most of the metabolites are excreted in the faeces. The elimination half-life in patients is 26–35 hours. Eltrombopag increases the concentrations of rosuvastatin and may interact with other HMGCoA reductase inhibitors.
A dose-ranging study randomised 118 patients to take a daily dose of eltrombopag 30 mg, 50 mg or 75 mg or placebo for up to six weeks. These patients had platelet counts below 30 x 109/L despite treatment. The trial end point was a platelet count of at least 50 x 109/L. This was reached by 28% of the patients given eltrombopag 30 mg, 70% of those given 50 mg and 81% of those given 75 mg. Only 11% of the placebo group reached the end point. The significant advantage of the 50 mg and 75 mg doses led to the trial being stopped.1
A starting dose of eltrombopag 50 mg was used in a subsequent phase III trial in patients who remained thrombocytopenic despite having had at least one previous therapy. The dose was increased to 75 mg if patients did not achieve a platelet count of 50 x 109/L after three weeks. Compared to the 38 patients randomised to placebo, there was a significantly greater response in the 76 patients randomised to eltrombopag. The target platelet count was achieved at six weeks by 59% of the eltrombopag group, but by only 16% of the placebo group.2
To assess the efficacy of longer-term treatment, 135 patients with platelet counts below 30 x 109/L were randomised to receive eltrombopag 50 mg for six months. The dose could be adjusted to 25 mg or 75 mg as needed. Another 62 patients were randomised to take a daily placebo. After six months of treatment 79% of the eltrombopag group, but only 28% of the placebo group, had achieved a platelet count of 50–400 x 109/L on at least one occasion. The response to eltrombopag tended to be maintained. Significantly more of the patients taking eltrombopag were able to reduce their other treatments.3
Diarrhoea, nausea and vomiting were common adverse events in the clinical trials. Eltrombopag is potentially hepatotoxic. A study of patients with liver disease had to be stopped because of adverse events such as portal vein thrombosis. Liver function should be tested before treatment, then every two weeks until the dose is stable and then monthly.
Cataracts were reported in animal studies of eltrombopag. An eye examination is therefore recommended for patients before and during treatment.
A potential hazard of a rapid rise in platelet count is thrombosis. In clinical trials, thromboembolic events occurred in 3.8% of patients.
Eltrombopag may increase the risk of bone marrow fibrosis. This is one possible cause for a loss of response to treatment.
The effect of eltrombopag wears off quickly. Within two weeks the patients' platelet counts will fall back to baseline levels or below. There may be an increased risk of bleeding at this time.
Although treatment with eltrombopag reduces bleeding it does not completely prevent it. During the six month study 19% of the patients taking eltrombopag and 31% of those taking placebo had bleeding as an adverse effect of treatment. This bleeding was serious in less than 1% of the eltrombopag group and 7% of the placebo group.3
Apart from oral administration, it is not known if eltrombopag has advantages over romiplostim. Until more is known about the long-term effects of stimulating the thrombopoietin receptor, the drug will be reserved for adult patients with an unsatisfactory response to other treatments.
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- Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237-47.
- Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009;373:641-8.
- Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011;377:393-402.
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.