7%
Myalgia 14% 2%
Pain in extremity 13% 5%
Abdominal Pain 11% 0%
Shoulder Pain 8% 0%
Dyspepsia 7% 0%
Paresthesia 6% 0%
Among 142 patients with chronic ITP who received Nplate in the single-arm extension study, the incidence rates of the adverse reactions occurred in a pattern similar to those reported in the placebo-controlled clinical studies.
6.2 Immunogenicity
As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein. Patients were screened for immunogenicity to romiplostim using a BIAcore-based biosensor immunoassay. This assay is capable of detecting both high- and low-affinity binding antibodies that bind to romiplostim and cross-react with TPO. The samples from patients that tested positive for binding antibodies were further eva luated for neutralizing capacity using a cell-based bioassay.
In clinical studies, the incidence of preexisting antibodies to romiplostim was 8% and the incidence of binding antibody development during Nplate treatment was 6%. The incidence of preexisting antibodies to endogenous TPO was 5% and the incidence of binding antibody development to endogenous TPO during Nplate treatment was 4%. Of the patients with positive antibodies to romiplostim or to TPO, two (0.4%) patients had neutralizing activity to romiplostim and none had neutralizing activity to TPO. No correlation was observed between antibody activity and clinical effectiveness or safety.
Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay used in detection and may be influenced by several factors, including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to romiplostim with the incidence of antibodies to other products may be misleading.
6.3 Postmarketing Experience
The following adverse reactions have been identified during post approval use of Nplate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Erythromelalgia
7 DRUG INTERACTIONS
No formal drug interaction studies of Nplate have been performed.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies of Nplate use in pregnant women. In animal reproduction and developmental toxicity studies, romiplostim crossed the placenta, and adverse fetal effects included thrombocytosis, postimplantation loss, and an increase in pup mortality. Nplate should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Pregnancy Registry: A pregnancy registry has been established to collect information about the effects of Nplate use during pregnancy. Physicians are encouraged to register pregnant patients, or pregnant women may enroll themselves in the Nplate pregnancy registry by calling 1-877-Nplate1 (1-877-675-2831).
In rat and rabbit developmental toxicity studies no evidence of fetal harm was observed at romiplostim doses up to 11 times (rats) and 82 times (rabbit) the maximum human dose (MHD) based on systemic exposure. In mice at doses 5 times the MHD, reductions in maternal body weight and increased postimplantation loss occurred.
In a prenatal and postnatal development study in rats, at doses 11 times the MHD, there was a |
