RESUMO
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of romiplostim, the first drug approved for use in patients with immune thrombocytopenic purpura (ITP). DATA SOURCES: Articles were identified through searches of MEDLINE (1966-January 2009) and International Pharmaceutical Abstracts (1970-January 2009) using the key words romiplostim and AMG 531. Searches were limited to articles published in English. The manufacturer was contacted for additional data. STUDY SELECTION AND DATA EXTRACTION: Clinical trials and pharmacokinetic data were selected for review. DATA SYNTHESIS: Romiplostim is a second-generation thrombopoietic receptor agonist that exerts its therapeutic effect by stimulating megakaryopoiesis. Subcutaneous therapy results in a dose-dependent increase in platelets; however, interindividual variability exists. Time to peak concentration is approximately 14 hours, and the elimination half-life is approximately 3.5 days (range 1-34). Romiplostim undergoes endothelial recirculation and is eliminated by the reticuloendothelial system. The results of 2 Phase 3, randomized, double-blind, placebo-controlled trials have demonstrated the efficacy of romiplostim for increasing platelet counts in patients with ITP refractory to other therapies, including splenectomy. Effects on platelets were transient and decreased within 2 weeks of discontinuing the drug. Interim results of an open-label extension study revealed that romiplostim has sustained efficacy and tolerability for up to 156 weeks at a dosage range of 1-17 microg/kg/wk (mean 5.9 +/- 3.9). The most common adverse effects include headache, fatigue, epistaxis, and contusion. Romiplostim is also under investigation for treatment of thrombocytopenia associated with myelodysplastic syndrome. The drug must be ordered directly from the manufacturer through a limited access program, and weekly subcutaneous injections are given in the clinic setting. CONCLUSIONS: Romiplostim is effective for the management of ITP in adults refractory to other therapies, including splenectomy.