BRIEF SUMMARY OF PRESCRIBING INFORMATION
Nplate® (romiplostim), for subcutaneous injection
WARNINGS AND PRECAUTIONS
Risk of Progression of Myelodysplastic Syndromes to Acute
Myelogenous Leukemia
Progression from myelodysplastic syndromes (MDS) to
acute myelogenous leukemia (AML) has been observed
in clinical trials with Nplate®. A randomized, double-blind,
placebo-controlled trial enrolling patients with severe
thrombocytopenia and International Prognostic Scoring
System (IPSS) low or intermediate-1 risk MDS was terminated
due to more cases of AML observed in the Nplate® treatment
arm. At the time of an interim analysis, among 219 MDS
patients randomized 2:1 to treatment with Nplate® or
placebo (147 Nplate®: 72 placebo), 11 patients showed
progression to AML, including nine on the Nplate® arm versus
two on the placebo arm. In addition, in peripheral blood
counts, the percentage of circulating myeloblasts increased
to greater than 10% in 28 patients, 25 of whom were
in the romiplostim treatment arm. Of the 28 patients
who had an increase in circulating myeloblasts to greater than
10%, eight of these patients were diagnosed to have AML,
and 20 patients had not progressed to AML. In four
patients, increased peripheral blood blast cell counts
decreased to baseline after discontinuation of Nplate®. In a
single-arm trial of Nplate® given to 72 patients with
thrombocytopenia related to MDS, eight (11%) patients
were reported as having possible disease progression,
and three patients had confirmation of AML during follow-up.
In addition, in three patients, increased peripheral blood
blast cell counts decreased to baseline after discontinuation
of Nplate®.
Nplate® is not indicated for the treatment of thrombocytopenia
due to MDS or any cause of thrombocytopenia other than
chronic ITP.
Thrombotic/Thromboembolic Complications
Thrombotic/thromboembolic complications may result from
increases in platelet counts with Nplate® use. Portal vein
thrombosis has been reported in patients with chronic liver
disease receiving Nplate®.
To minimize the risk for thrombotic/thromboembolic
complications, do not use Nplate® in an attempt to normalize
platelet counts. Follow the dose adjustment guidelines to
achieve and maintain a platelet count of 50 x 109/L [see
Dosage and Administration].
Loss of Response to Nplate®
Hyporesponsiveness or failure to maintain a platelet response
with Nplate® should prompt a search for causative factors,
including neutralizing antibodies to Nplate® [see Adverse
Reactions]. To detect antibody formation, submit blood
samples to Amgen (1-800-772-6436). Amgen will assay these
samples for antibodies to Nplate® and thrombopoietin (TPO).
Discontinue Nplate® if the platelet count does not increase to
a level sufficient to avoid clinically important bleeding after
4 weeks at the highest weekly dose of 10 mcg/kg.
Laboratory Monitoring
Obtain CBCs, including platelet counts, weekly during
the dose-adjustment phase of Nplate® therapy and then
monthly following establishment of a stable Nplate® dose.
Obtain CBCs, including platelet counts, weekly for at least 2
weeks following discontinuation of Nplate® [see Dosage and
Administration].
ADVERSE REACTIONS
The following serious adverse reactions are discussed in
greater detail in other sections:
• Progression of Myelodysplastic Syndromes
[see Warnings and Precautions]
• Thrombotic/Thromboembolic Complications
[see Warnings and Precautions]
• Loss of Response to Nplate®
[see Warnings and Precautions]
• Laboratory Monitoring
[see Warnings and Precautions]
Clinical Trials Experience
Because clinical trials are conducted under widely varying
conditions, adverse reaction rates observed in the clinical trials
of a drug cannot be directly compared to rates in the clinical
trials of another drug and may not reflect the rates observed
in practice.
The data described below reflect Nplate® exposure to 271
patients with chronic ITP, aged 18 to 88, of whom 62% were
female. Nplate® was studied in two randomized, placebocontrolled, double-blind studies that were identical in design,
with the exception that Study 1 evaluated nonsplenectomized
patients with ITP and Study 2 evaluated splenectomized
patients with ITP. Data are also reported from an open-label,
single-arm study in which patients received Nplate® ove ȁ