08/22. Also, epoetin should be used only in cancer patients who are undergoing chemotherapy or radiation therapy. One aspect of the administration's plan calls for international mechanisms that can help strengthen lab safety and biosecurity practices around the world. Avoid excess or vigorous agitation: DO NOT SHAKE. Discard any unused portion. Patterson AM, Vemula S, Plett PA, Sampson CH, Chua HL, Fisher A, Wu T, Sellamuthu R, Feng H, Katz BP, DesRosiers CM, Pelus LM, Cox GN, MacVittie TJ, Orschell CM. It's a prescription drug that treats low platelet level in certain people. No apparent correlation was observed between antibody activity and clinical effectiveness or safety. Administer Nplate only with a syringe that contains 0.01 mL graduations. The efficacy of Nplate was studied in a randomized, blinded, placebo-controlled study in a non-human primate model of radiation injury. Kumar VP, Holmes-Hampton GP, Biswas S, Stone S, Sharma NK, Hritzo B, Guilfoyle M, Eichenbaum G, Guha C, Ghosh SP. The safety and efficacy of Nplate in adults with ITP were assessed in two double-blind, placebo-controlled clinical studies, an open-label single-arm study, and in an open-label extension study. Those who are not receiving chemotherapy or radiation . Discontinue Nplate if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of Nplate therapy at the maximum weekly dose of 10 mcg/kg This can cause impaired blood clotting due to low platelet counts and potentially life-threatening bleeding. You are encouraged to report negative side effects of prescription drugs to the FDA. You may report side effects to FDA at 1-800-FDA-1088. Among 291 adult patients with 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. In this study, these findings were not observed in animals after a 4-week post treatment recovery period. Due to the potential for serious adverse reactions in a breastfed child from Nplate, advise women not to breastfeed during treatment with Nplate. The HHS didnt comment on when the decision to order the drug was made or whether it predated the Russian invasion of Ukraine in February, but it noted that the department began supporting the development of the drug back in 2019 after earlier involvement from the National Institutes of Health. The supply of Nplate has been procured "to save lives following radiological and nuclear emergencies", according to the HSS announcement. Adult patients who lacked response or lost response to Nplate or a non-US approved romiplostim product were enrolled. "These platelets are produced from megakaryocytes. between antibody activity and clinical effectiveness or safety.1,4, Review Nplate safety profile in adults with newly Review dosing and titration for once-weekly Nplate.1 Learn more, Nplate is a TPO mimetic that works to target Because of the uncertainty associated with extrapolating animal efficacy data to humans, the selection of a human dose for Nplate is aimed at providing platelet response to Nplate that is similar to that observed in efficacy studies conducted in animals. Thrombocytopenia results from a variety of conditions, including radiation, chemotherapy, autoimmune disease, bone marrow disorders, pathologic conditions associated with surgical procedures, hematopoietic stem cell transplant (HSCT), and hematologic disorders associated with severe aplastic anemia. A transient platelet response was the achievement of any weekly platelet counts 50 109/L for any 4 weeks during the treatment period without a durable platelet response. An overall platelet response was defined as a durable or a transient platelet response. activity to romiplostim and none had neutralizing activity to TPO. On October 4, the United States Department for Health and Human Services (HHS) announced it was purchasing a supply of the drug Nplate "as part of long-standing, ongoing efforts to be better prepared to save lives following radiological and nuclear emergencies.". Bottom line, we are watching everything, but this shouldnt be used as a data point to assume there is a greater threat than people anticipate, he said. Patients received single weekly SC injections of Nplate over a 12-month treatment period, with individual dose adjustments to maintain platelet counts (50 x 109/L to 200 x 109/L). Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate. Nplate may harm your unborn baby. Nplate can cause serious side effects, including: See What are the possible side effects of Nplate? for other side effects of Nplate. Verify that the syringe contains the correct dosage. The primary efficacy endpoint was survival. Prior ITP treatments included corticosteroids, immunoglobulins and anti-D immunoglobulins. Yang BB, Doshi S, Arkam K, Franklin J, Chow AT. The samples from patients that tested positive for binding antibodies were further evaluated for neutralizing capacity using a cell-based bioassay. In other words, despite President Joe Biden's warning that the risk of nuclear Armageddon is the highest it has been since the Cuban missile crisis, the purchase of the drug for radiation sickness is coincidental, according to the HHS. The patients had been diagnosed with ITP for approximately 2 years and had received a median of three prior ITP treatments. Epub 2020 Jul 15. Your healthcare provider may need to check your bone marrow for this problem during treatment with Nplate. sharing sensitive information, make sure youre on a federal Following discontinuation of Nplate, thrombocytopenia and risk of bleeding may develop that is worse than that experienced prior to the Nplate therapy. 2. He previously covered the biotech and pharmaceutical industry with CNBC. 2010;8(6):1372-1382. Thrombocytopenia; hematopoietic acute radiation syndrome; medical countermeasure; romiplostim. Even with Nplate therapy, patients should continue to avoid situations or medications that may increase the risk for bleeding. Of these 9 patients, 2 patients had pre-existing binding non-neutralizing antibodies to TPO. This trial consisted of a 58-week study period with a 5-year long-term follow-up phase. The incidence of new binding antibody development was 3.8% (7/184) to romiplostim and 2.2% (4/184) were positive for binding, non-neutralizing antibodies to TPO; two patients were positive for binding antibodies to both romiplostim and TPO. Over a 12-week treatment period dose was titrated up to a maximum of 10 mcg/kg weekly of either Nplate or placebo in an effort to maintain a target platelet count of 50 109/L to 250 109/L. The https:// ensures that you are connecting to the The percentage of patients with at least 2 prior ITP therapies (predominantly immunoglobulins and corticosteroids) was 81% in the group treated with Nplate and 70% in the group treated with placebo. In mice at doses 5 times the MHD, reductions in maternal body weight and increased postimplantation loss occurred. The hematopoietic system is one of the most sensitive tissues to ionizing radiation, and radiation doses from 2 to 10 gray can result in death from bleeding and infection if left . Reconstituted product with Sterile Water for Injection, USP that has not been further diluted can remain in the original vial at room temperature 25C (77F) or be refrigerated at 2C to 8C (36F to 46F) for up to 24 hours following reconstitution. Acute radiation sickness occurs when a person's body is exposed to a high dose of radiation that reaches the internal organs within seconds. Advise females of reproductive potential to inform their prescriber of a known or suspected pregnancy [see, Advise women not to breastfeed during treatment with Nplate [see, Injection of too much Nplate may cause a dangerous increase in your blood platelet count and serious side effects. Nplate for ITP is given by your healthcare provider as an injection under. As with all therapeutic proteins, there is a potential for immunogenicity. are breastfeeding or plan to breastfeed. We need products that can be used longer, he said. Study 2 evaluated patients who had undergone a splenectomy. Do not shake. Inform patients of the following risks and considerations for Nplate: The carcinogenic potential of romiplostim has not been evaluated. Keywords: In the baseline low IPSS group, there was a higher incidence of death in the Nplate arm [41.3% (19/46)] compared to the placebo arm [30.4% (7/23)] (HR [95% CI] = 1.59 [0.67, 3.80]). Nplate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Animals received medical management consisting of intravenous or subcutaneous fluids, anti-ulcer medication, anti-emetic medication, analgesics, antimicrobials, and other support as required. The use of Nplate to increase survival in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in adult animals. If not used within the 30 days, discard Nplate. Nplate (romiplostim) for injection is supplied as a sterile, preservative-free, solid white lyophilized powder in single-dose vials that deliver 125 mcg (NDC-55513-223-01), 250 mcg (NDC 55513-221-01) and 500 mcg (NDC 55513-222-01) of romiplostim. The use of animal models in radiation research allows for the simulation of the biological effects of exposure in humans . Overdoses due to medication errors have been reported in patients receiving Nplate. Nineteen confirmed pediatric patients were included in the postmarketing registry study. Reconstitute Nplate with Sterile Water for Injection, USP. government site. Nplate is also used to treat people including newborns who have been exposed to high levels of radiation (acute radiation syndrome). Nplate is indicated for the treatment of thrombocytopenia in: Nplate is indicated to increase survival in adults and in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation [see Clinical Studies]. Following Nplate discontinuation in Studies 1 and 2, seven patients maintained platelet counts of 50 109/L. 5 days/week, 6 days/week, or all 7 days/week, depending on the animal's responsiveness and any potential side effects. It helps stimulate. Ultraviolet Radiation Natural sunlight stimulates the production of vitamin D, an important nutrient for the formation of healthy bones. The drug can be used to treat adults and children," HHS said. Herein, we present the results of an analysis in mice of romiplostim as a medical countermeasure to improve survival and PLT recovery following acute radiation.Materials and methods: Male and female C57BL/6J mice (11 - 12 weeks of age, n = 21/sex/group) were total body irradiated (TBI) with 6.8 Gy X-rays that reduces 30-day survival to 30% (LD70/30). Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding. Results from population modeling and simulation indicate that a single 10 mcg/kg subcutaneous dose of Nplate would result in clinically relevant effects on incidence rate and duration of severe thrombocytopenia in patients acutely exposed to myelosuppressive doses of radiation. development via the same pathway as eTPO.1,3. Nplate is a prescription medicine also used to treat people including newborns who have been exposed to high levels of radiation (acute radiation syndrome). Two vial presentations are available, which contain a sufficient amount of active ingredient to provide either 250 mcg or 500 mcg of deliverable romiplostim, respectively. In the same study, an exploratory cohort of n=40 animals received Nplate (5mg/kg) on day 1 and pegfilgrastim (0.3mg/kg) on days 1 and 8 post-irradiation. Once stored at room temperature, do not place back in the refrigerator. Methods We searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical . Inactive ingredients: L-histidine, mannitol, polysorbate 20, sucrose, and hydrochloric acid. Mitigative efficacy of the clinical dosage administration of granulocyte colony-stimulating factor and romiplostim in mice with severe acute radiation syndrome. Pill Identifier Tool Quick, Easy, Pill Identification, Drug Interaction Tool Check Potential Drug Interactions, Pharmacy Locator Tool Including 24 Hour, Pharmacies. Nplate is a prescription drug produced by California-based biotechnology company Amgen. Thats because, he said, the $290 million purchase of Nplate amounts to about 50,000 courses of the drug, less than the amount he would expect the U.S. to buy if the nation were close to a nuclear war with Russia. The Democratic Party Should Set Higher Standards | Opinion, The Democratic Party is Becoming Less Inclusive | Opinion. Epub 2019 Jun 21. Nplate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. There were no antibodies detected to TPO. 4. 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. See Table 2 for final concentrations. Your healthcare provider will check your platelet count every week and change your dose of Nplate as needed. Included as part of the "PRECAUTIONS" Section. All patients were negative for neutralizing activity to TPO. What Are the Best PsA Treatments for You? Follow the dose adjustment guidelines [see DOSAGE AND ADMINISTRATION]. Platelet responses were excluded for 4 weeks after receiving rescue medications. Disclaimer, National Library of Medicine Administration of Prepared Nplate Solution. Calculate Volume to Administer by dividing the Calculated Patient Dose (mcg) by the final concentration. Careers. Of the 250 patients, 210 (84.0%) entered the long-term follow-up phase of this study. refillable drug delivery devices and methods of use thereof: : ep15773877.4: : 2015-04-06: (): ep3125866a1: () Be sure to tell your healthcare provider about all of your medical conditions, including if you: Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products. Newsweek has contacted the HHS for comment. 2020 Jan;96(1):155-166. doi: 10.1080/09553002.2019.1625488. Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Mechanism of action representations are for Do not administer more than one dose from a vial. Platelet counts and CBCs must be performed weekly until a stable Nplate dose has been achieved; thereafter, platelet counts and CBCs must be performed monthly while taking Nplate. Platelet volume also increased more rapidly after romiplostim injection. Obtain CBCs, including platelet counts, weekly for at least 2 weeks following discontinuation of Nplate. Of the Advise the patient to read the FDA-approved patient labeling (Medication Guide). The pharmacokinetics of romiplostim have been evaluated in pediatric patients 1 year and older with ITP [see CLINICAL PHARMACOLOGY]. Despite pandemic slowdown, biosimilars keep gaining market share in the US, Amgen report says. A TPO receptor agonist, Nplate is an Fc-peptide fusion protein (peptibody) that contains 2 single-chain subunits, each having a region with 2 TPO receptor-binding domains. 2022 Aug;45(8):558-571. doi: 10.1007/s12272-022-01400-7. diagnosed/persistent ITP. Greg Burel, the former director of the Strategic National Stockpile, agreed, saying that he doesn't think the HHS' purchase of the drug is related to the Russian invasion of Ukraine in February. Study 5 results are shown in Table 6. Epub 2022 Aug 11. Visually inspect the reconstituted solution for particulate matter and/or discoloration. Nplate, manufactured by U.S. drugmaker Amgen, was approved by the Food and Drug Administration in 2021 to treat injuries caused by acute radiation syndrome, also known as radiation sickness. 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.