Cases of thromboembolic events (TEEs), including portal vein thrombosis, have been reported in patients with chronic liver disease receiving romiplostim. Romiplostim should be used with caution in these populations. Dose adjustment guidelines should be followed (see section 4.2).

Progression of existing Myelodysplastic Syndromes (MDS)

A positive benefit/risk for romiplostim is only established for the treatment of thrombocytopenia associated with chronic ITP and romiplostim must not be used in other clinical conditions associated with thrombocytopenia.

The diagnosis of ITP in adults and elderly patients should have been confirmed by the exclusion of other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be excluded. A bone marrow aspirate and biopsy should normally have been done over the course of the disease and treatment, particularly in patients over 60 years of age, for those with systemic symptoms or abnormal signs such as increased peripheral blast cells.

In clinical studies of treatment with romiplostim in patients with MDS, cases of transient increases in blast cell counts were observed and cases of MDS disease progression to AML were reported. Based on available data from a randomized trial, there were numerically more subjects in the romiplostim arm with disease progression to AML (placebo 2/72, romiplostim 9/147) and with an increase in circulating blasts to greater than 10% (placebo 3/72, romiplostim 25/147). Of the cases of MDS disease progression to AML that were observed, patients with RAEB-1 classification of MDS at baseline were more likely to have disease progression to AML compared to lower risk MDS.

Romiplostim must not be used for the treatment of thrombocytopenia due to MDS or any other cause of thrombocytopenia other than ITP outside of clinical trials.

Loss of response to romiplostim

A loss of response or failure to maintain a platelet response with romiplostim treatment within the recommended dosing range should prompt a search for causative factors, including immunogenicity (see section 4.8) and increased bone marrow reticulin (see above).

Effects of romiplostim on red and white blood cells

Alterations in red (decrease) and white (increase) blood cell parameters have been observed in non-clinical toxicology studies (rat and monkey) but not in ITP patients. Monitoring of these parameters should be considered in patients treated with romiplostim.

4.5 Interaction with other medicinal products and other forms of interaction

 No interaction studies have been performed. The potential interactions of romiplostim with co-administered medicinal products due to binding to plasma proteins remain unknown.

Medicinal products used in the treatment of ITP in combination with romiplostim in clinical studies included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin. Platelet counts should be monitored when combining romiplostim with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range (see section 4.2).

Corticosteroids, danazol, and azathioprine use may be reduced or discontinued when given in combination with romiplostim (see section 5.1). Platelet counts should be monitored when reducing or discontinuing other ITP treatments in order to avoid platelet c