Romiplate Special Precautions

The following special warnings and precautions have been actually observed or are potential class effects based on the pharmacological mechanism of action of thrombopoietin (TPO) receptor stimulators.
Reoccurrence of thrombocytopenia and bleeding after cessation of treatment: Thrombocytopenia is likely to reoccur upon discontinuation of treatment with romiplostim. There is an increased risk of bleeding if romiplostim treatment is discontinued in the presence of anticoagulants or anti-platelet agents. Patients should be closely monitored for a decrease in platelet count and medically managed to avoid bleeding upon discontinuation of treatment with romiplostim. It is recommended that, if treatment with romiplostim is discontinued, ITP treatment be restarted according to current treatment guidelines. Additional medical management may include cessation of anticoagulant and/or antiplatelet therapy, reversal of anticoagulation, or platelet support.
Increased bone marrow reticulin: Increased bone marrow reticulin is believed to be a result of TPO receptor stimulation, leading to an increased number of megakaryocytes in the bone marrow, which may subsequently release cytokines. Increased reticulin may be suggested by morphological changes in the peripheral blood cells and can be detected through bone marrow biopsy. Therefore, examinations for cellular morphological abnormalities using peripheral blood smear and complete blood count (CBC) prior to and during treatment with romiplostim are recommended. See Adverse Reactions for information on the increases of reticulin observed in romiplostim clinical trials.
If a loss of efficacy and abnormal peripheral blood smear is observed in patients, administration of romiplostim should be discontinued, a physical examination should be performed, and a bone marrow biopsy with appropriate staining for reticulin should be considered. If available, comparison to a prior bone marrow biopsy should be made. If efficacy is maintained and abnormal peripheral blood smear is observed in patients, the physician should follow appropriate clinical judgment, including consideration of a bone marrow biopsy, and the risk-benefit of romiplostim and alternative ITP treatment options should be re-assessed.
Thrombotic/thromboembolic complications: Platelet counts above the normal range present a risk for thrombotic/thromboembolic complications. The incidence of thrombotic/thromboembolic events observed in clinical trials was 6.0% with romiplostim and 3.6% with placebo. Caution should be used when administering romiplostim to patients with known risk factors for thromboembolism including but not limited to inherited (e.g. Factor V Leiden) or acquired risk factors (e.g. ATIII deficiency, antiphospholipid syndrome), advanced age, patients with prolonged periods of immobilisation, malignancies, contraceptives and hormone replacement therapy, surgery/trauma, obesity, and smoking.
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 Dosage & Administration).
Medication errors: Medication errors including overdose and underdose have been reported in patients receiving Romiplate, dose calculation and dose adjustment guidelines should be followed.
Overdose may result in an excessive increase in platelet counts associated with thrombotic/thromboembolic complications. If the platelet counts are excessively increased, discontinue Romiplate and monitor platelet counts. Reinitiate treatment with Romiplate in accordance with dosing and administration recommendations. Underdose may result in lower than expected platelet counts and potential for bleeding. Platelet counts should be monitored in patients receiving Romiplate (see Dosage & Administration, Precautions and Overdosage).
Progression of existing Myelodysplastic Syndromes (MDS): A positive benefit/risk for romiplostim is only established for the treatment of thrombocytopenia associated with ITP (see Indications/Uses) 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 adult clinical studies of treatment with romiplostim in patients with MDS, cases of transient blast cell increases were observed and cases of MDS disease progression to AML were reported. In a randomised placebo-controlled trial in MDS subjects, treatment with romiplostim was prematurely stopped due to a numerical excess of disease progression to AML and an increase in circulating blasts greater than 10% in patients receiving romiplostim. 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 use for the treatment of thrombocytopenia due to MDS or any other cause of thrombocytopenia other than ITP outside of clinical trials.
Aplastic anaemia refractory to conventional therapy: Some patients with aplastic anaemia are known to progress to MDS or acute myeloid leukaemia (AML) during follow-up. In international clinical studies, some patients with aplastic anaemia refractory to conventional therapy were found to have chromosome abnormalities after administration of Romiplate, although the causality was unclear.
During treatment with Romiplate, a complete blood count including a differential leukocyte count and peripheral blood smear should be tested regularly in order to assess immature cells and morphological abnormalities, as well as cytopenia. If such abnormalities are found, consider a bone marrow test (including a chromosomal evaluation) to determine whether Romiplate treatment should be continued.
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 Adverse Reactions) and increased bone marrow reticulin (see as previously mentioned).
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) as well as ITP patients. Concurrent anaemia and leucocytosis (within a 4-week window) may occur in patients regardless of splenectomy status, but have been seen more often in patients who have had a prior splenectomy. Monitoring of these parameters should be considered in patients treated with romiplostim.
Laboratory monitoring: Monitor CBCs, including platelet counts and peripheral blood smears, prior to initiation, throughout, and following discontinuation of Romiplate therapy. Prior to the initiation of Romiplate, examine the peripheral blood differential to establish the baseline extent of red and white blood cell abnormalities. Obtain CBCs, including platelet counts and peripheral blood smears, weekly during the dose adjustment phase of Romiplate therapy and then monthly following establishment of a stable Romiplate dose. Obtain CBCs, including platelet counts, weekly for at least 2 weeks following discontinuation of Romiplate.
Effects on ability to drive and use machines: Romiplate has moderate influence on the ability to drive and use machines. In clinical trials, mild to moderate, transient bouts of dizziness were experienced by some patients.