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Cytokines for Treatment of Acute Exposure to
Myelosuppressive Doses of Radiation: Hematopoietic Subsyndrome
of Acute Radiation Syndrome (H-ARS)

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Myeloid Cytokines

Key Clinical Information
  • The goals of using a myeloid colony-stimulating factor for radiation-induced myelosuppression are to:
    • Improve survival of adults and children exposed to myelosuppressive doses of radiation
    • Shorten the duration of severe neutropenia
    • Minimize the severity of neutropenia-associated complications, including infection
  • Initiation of treatment in a radiation incident should be strongly considered for patients who:
    • Are likely to have received ≥2 Gray (Gy) whole body exposure or ≥2 Gy significant partial body exposure
    • Are likely to have an absolute neutrophil count of ≤500 cells/mm3
    • Will likely have prolonged periods of significant neutropenia (See radiation effects on blood counts diagram).
  • Patients with radiation exposure plus trauma and/or burns have worse clinical outcomes compared to radiation exposure alone. This may impact the decision to administer cytokines (refer to combined injury triage card).
  • The CDC is responsible for creating and issuing Emergency Use Instructions (EUIs) regarding drug use in emergencies.
    • The EUI authority allows CDC to facilitate the availability of streamlined information about the use of eligible, approved MCMs needed during public health emergencies without FDA needing to issue an Emergency Use Authorization (EUA).

Cytokine

Key Information

G-CSF: filgrastim
(Neupogen drug label , Revised 04/2023)

  • Estimate a patient's absorbed radiation dose  (i.e., level of radiation exposure) based on radiation dose reconstruction information , biodosimetry , if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics . Obtain CBC with differential prior to initiating cytokine administration when lab and drug supplies are adequate.

  • Administer Neupogen as soon as possible after suspected or confirmed exposure to radiation doses ≥2 Gy. Do NOT delay administration of Neupogen if a complete blood count (CBC) is not readily available.

  • Standard dosing when supplies are adequate

    • Administer 10 mcg/kg/day as a single daily subcutaneous injection in adults and children for the FDA-approved indication of acute exposure to myelosuppressive doses of radiation.

    • Continue daily administration until absolute neutrophil count remains greater than 1,000/mm3 (= 1.0 x 109 cells/L) for 3 consecutive (daily) CBCs or exceeds 10,000/mm3 (= 10 x 109 cells/L) after a radiation-induced nadir.

    • Vial sizes are 300 mcg and 480 mcg. For a 70 kg person, 2 vials of either size would be the appropriate dose. It would be reasonable to indicate a maximum dose like 960 mcg OR two vials per dose though this is not uniformly agreed upon. Note that if the appropriate dose requires administration of 2 vials, separate injection sites would be required.

    • See FDA-approved drug label for full prescribing information.

  • Strategies for dosing when drug supplies are insufficient to treat all patients at full dose, with plan to return to standard dosing as soon as adequate drug supplies arrive

    • The standard starting dose for children is 5 mcg/kg which is then titrated for effect as needed.

    • For adults, start with the lower dose of 5mcg/kg/day instead of 10 mcg/kg/day; dose less frequently than daily until adequate supplies arrive to treat all patients at the higher daily dose; stopping drug when ANC reaches 5,000/mm3 (= 5.0 x 109 cells/L) rather than 10,000/mm3 (= 10.0 x 109 cells/L). These recommendations, however, are NOT included in the FDA drug label.

    • Lab monitoring - If possible, obtain a baseline complete blood count (CBC) prior to administration of first dose and then serial CBCs about every third day until the absolute neutrophil count (ANC) remains greater than 1,000/mm3 (= 1 x 109 cells/L) for 3 consecutive CBCs. Do NOT delay administration of Neupogen if a CBC is not readily available.

Neupogen Biosimilar:

G-CSF: filgrastim-txid
(Nypozi Drug Label , Revised 06/2024)

  • Estimate a patient's absorbed radiation dose  (i.e., level of radiation exposure) based on radiation dose reconstruction information , biodosimetry, if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics. Obtain CBC with differential prior to initiating cytokine administration when lab and drug supplies are adequate.

  • Administer Nypozi as soon as possible after suspected or confirmed exposure to radiation doses ≥2 Gy. Do NOT delay administration of Neupogen if a complete blood count (CBC) is not readily available.

  • Standard dosing when supplies are adequate

    • Administer 10 mcg/kg/day as a single daily subcutaneous injection in adults and children for the FDA-approved indication of acute exposure to myelosuppressive doses of radiation.

    • Continue daily administration until absolute neutrophil count remains greater than 1,000/mm3 (= 1.0 x 109 cells/L) for 3 consecutive (daily) CBCs or exceeds 10,000/mm3 (= 10 x 109 cells/L) after a radiation-induced nadir.

    • Vial sizes are 300 mcg and 480 mcg. For a 70 kg person, 2 vials of either size would be the appropriate dose. It would be reasonable to indicate a maximum dose like 960 mcg OR two vials per dose though this is not uniformly agreed upon. Note that if the appropriate dose requires administration of 2 vials, separate injection sites would be required.

    • See FDA-approved drug label for full prescribing information.

  • Strategies for dosing when drug supplies are insufficient to treat all patients at full dose, with plan to return to standard dosing as soon as adequate drug supplies arrive

    • The standard starting dose for children is 5 mcg/kg which is then titrated for effect as needed.

    • For adults, start with the lower dose of 5mcg/kg/day instead of 10 mcg/kg/day; dose less frequently than daily until adequate supplies arrive to treat all patients at the higher daily dose; stopping drug when ANC reaches 5,000/mm3 (= 5.0 x 109 cells/L) rather than 10,000/mm3 (= 10.0 x 109 cells/L). These recommendations, however, are NOT included in the FDA drug label.

  • Lab monitoring - If possible, obtain a baseline complete blood count (CBC) prior to administration of first dose and then serial CBCs about every third day until the absolute neutrophil count (ANC) remains greater than 1,000/mm3 (= 1 x 109 cells/L) for 3 consecutive CBCs. Do NOT delay administration of Nypozi if a CBC is not readily available.

Pegylated G-CSF: pegfilgrastim
(Neulasta drug label, Revised: 02/2021)

  • Estimate a patient's absorbed radiation dose  (i.e., level of radiation exposure) based on radiation dose reconstruction information , biodosimetry , if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics . Obtain CBC with differential prior to initiating cytokine administration when lab and drug supplies are adequate.

  • Administer Neulasta as soon as possible after suspected or confirmed exposure to radiation doses ≥2 Gy. Do NOT delay administration of Neulasta if a CBC is not readily available.

  • Standard dosing - when supplies are adequate

    • In adults and children weighing ≥45 kg, two doses, 6 mg each, administered subcutaneously one week apart for the FDA-approved indication of acute exposure to myelosuppressive doses of radiation.

    • In pediatric patients weighing less than 45 kg, refer to table in Neulasta drug label for dose calculated by weight. Administer two doses of drug subcutaneously one week apart.

    • Despite the weight-based pediatric dosing, it is not possible to directly dose pediatric patients less than 45 kg. For pediatric patients in a hospital, the exact dose would be prepared under a laminar flow hood by hospital staff. Dosing pediatric outpatients, including during a radiological or nuclear public health emergency, currently has a risk of contamination and medication dosing errors. The FDA has received medication error reports and has requested Amgen to submit pediatric assessments as described in section 505B(a)(2)(A) of the FD&C Act, including development of an “appropriate formulation” (presentation) that can be used to administer Neulasta directly and accurately to pediatric patients who weigh less than 45 kg.

    • See FDA-approved drug label for full prescribing information.

  • Strategies for dosing when drug supplies are insufficient to treat all patients at full dose, with plan to return to standard dosing as soon as adequate drug supplies arrive

    • Public health authorities might recommend giving the first dose of Neulasta (day 1) and require a CBC prior to the second dose (day 8) in order to consider whether the second dose is necessary or possibly delay it. Subject matter experts recommend NOT administering the second dose if the ANC exceeds 5,000/mm3 (= 5.0 x 109 cells/L). These recommendations, however, are NOT included in the FDA drug label.

    • Lab monitoring - If possible, obtain a baseline CBC with differential prior to administration of the first dose. A CBC should be obtained prior to administration of the second dose of Neulasta. Subject matter experts recommend NOT administering the second dose if absolute neutrophil count is greater than 5,000/mm3 (= 5.0 x 109 cells/L), regardless of drug scarcity. Do NOT delay initial administration of Neulasta if a CBC is not readily available.

Neulasta Biosimilars:

Pegylated G-CSF: pegfilgrastim-cbqv
(Udenyca drug label, Revised: 03/2023)

Pegylated G-CSF: pegfilgrastim-fpgk
(Stimufend drug label, revised: 09/2023)

Pegylated G-CSF: pegfilgrastim-bmez
(Ziextenzo drug label, revised 02/2024)

  • Estimate a patient's absorbed radiation dose  (i.e., level of radiation exposure) based on radiation dose reconstruction information , biodosimetry , if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics . Obtain CBC with differential prior to initiating cytokine administration when lab and drug supplies are adequate.

  • Administer Udenyca, Stimufend, or Ziextenzo as soon as possible after suspected or confirmed exposure to radiation doses ≥2 Gy. Do NOT delay administration if a CBC is not readily available.

  • Standard dosing – when supplies are adequate:

    • In adults and children weighing ≥ 45 kg , two doses, 6 mg each, administered subcutaneously one week apart for the FDA-approved indication of acute exposure to myelosuppressive doses of radiation.

    • In pediatric patients weighing less than 45 kg, refer to the pediatric dosing tables on the drug label for dose calculated by weight. Administer two doses of drug subcutaneously one week apart.

    • Pediatric dosing tables:

    • Despite the weight-based pediatric dosing, it is not possible to directly dose pediatric patients less than 45 kg. For pediatric patients in a hospital, the exact dose would be prepared under a laminar flow hood by hospital staff. Dosing pediatric outpatients, including during a radiological or nuclear public health emergency, currently has a risk of contamination and medication dosing errors. As there are dosing errors for Neulasta in pediatric patients less than 45 kg, Udenyca, Stimufend, and Ziextenzo would be expected to be associated with the same type of dosing errors. The FDA has issued an order letter to Coherus BioScience (Udenyca), Fresenius Kabi (Stimufend), and Sandoz (Ziextenzo) and requested to submit pediatric assessments as described in section 505B(a)(2)(A) of the FD&C Act, including development of an “appropriate formulation” (presentation) that can be used to administer directly and accurately to pediatric patients who weigh less than 45 kg.

    • See FDA drug label for full prescribing information. 

  • Strategies for dosing when drug supplies are insufficient to treat all patients at full dose, with plan to return to standard dosing as soon as adequate drug supplies arrive.

    • Public health authorities might recommend giving the first dose of Udenyca, Stimufend, or Ziextenzo (day 1) and require a CBC prior to the second dose (day 8) in order to consider whether the second dose is necessary or possibly delay it. Subject matter experts recommend NOT administering the second dose if the ANC exceeds 5,000/mm3 (= 5.0 x 109 cells/L). These recommendations, however, are NOT included in the FDA drug label.

  • Lab monitoring - If possible, obtain a baseline CBC with differential prior to administration of the first dose. A CBC should be obtained prior to administration of the second dose of Udenyca, Stimufend, or Ziextenzo. Subject matter experts recommend NOT administering the second dose if absolute neutrophil count is greater than 5,000/mm3 (= 5.0 x 109 cells/L), regardless of drug scarcity. Do NOT delay initial administration if a CBC is not readily available.

GM-CSF: sargramostim
(Leukine drug label, Revised 05/2022)

  • Estimate a patient's absorbed radiation dose (i.e., level of radiation exposure) based on radiation dose reconstruction information , biodosimetry , if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics. Obtain CBC with differential prior to initiating cytokine administration when lab and drug supplies are adequate.

  • Administer Leukine as soon as possible after suspected or confirmed exposure to radiation doses ≥2 Gy.

  • Standard dosing – Leukine is a subcutaneous injection administered once daily as follows:

    • 7 mcg/kg in adult and pediatric patients weighing greater than 40 kg

    • 10 mcg/kg in pediatric patients weighing 15 kg to 40 kg

    • 12 mcg/kg in pediatric patients weighing less than 15 kg

    • Continue administration of Leukine until absolute neutrophil count remains greater than 1,000/mm3 (= 1.0 x 109 cells/L) for 3 consecutive CBCs or exceeds 10,000/mm3 (= 10 x 109 cells/L) after a radiation-induced nadir.

    • See FDA-approved drug label for full prescribing information

  • Lab monitoring when Leukine supply is scarce - Obtain a baseline CBC with differential if possible, and then serial CBCs approximately every third day until the ANC remains greater than 1,000/mm3 for three consecutive CBCs. Do NOT delay initial administration of Leukine if a CBC is not readily available.
G-CSF = granulocyte colony-stimulating factor
GM-CSF = granulocyte-macrophage colony-stimulating factor

Other myeloid colony-stimulating factors (G-CSFs, GM-CSFs)
  • The drugs below are in clinical use for various indications but are NOT approved by the FDA, as of June 21, 2024, for the specific indication of acute exposure to myelosuppressive doses of radiation.
    • pegfilgrastim-pbbk (Fylnetra®) (Kashiv BioSciences, LLC)
General comments:
  • This class of drugs is referred to by various names.
    • Myeloid, white cell, or leukocyte cytokines
    • Myeloid, white cell, or leukocyte growth factors
    • Myeloid, white cell, or leukocyte colony-stimulating factors (CSFs)
  • Specific individual drugs in this class target specific kinds of myeloid cell(s).
    • Neutrophils only (e.g., filgrastim, a G-CSF)
    • Neutrophils and macrophages (e.g., sargramostim, a GM-CSF)
  • Listing on this page does NOT mean that each product is in the U.S. Strategic National Stockpile (SNS).
  • See REMM Exposure Algorithm for the clinical context for using these drugs to treat acute exposure to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of ARS).
Procuring and using myeloid cytokines during large mass casualty incidents
  • Neupogen, Neulasta, Leukine, Udenyca, Stimufend, Ziextenzo, and Nypozi are FDA-approved for the indication of acute exposure to myelosuppressive doses of radiation.
  • If there are very significant shortages of medical countermeasures, including myeloid cytokines, public health authorities may recommend modification of standard dosing schedules.
    • Neupogen and Nypozi: Public health authorities might, for example, recommend using Neupogen at a dose of 5 mcg/kg/day instead of 10 mcg/kg/day, dosing perhaps less frequently than daily until adequate supplies arrive to treat all patients at the higher daily dose, and/or stopping administration when ANC reaches 5,000/mm3 (= 5.0 x 109 cells/L) rather than 10,000/mm3 (= 10.0 x 109 cells/L). These recommendations, however, are NOT included in the FDA drug label.
    • Neulasta, Udenyca, Stimufend, and Ziextenzo: Public health authorities might recommend giving the first dose (day 1) and require a CBC prior to the second dose (day 8) in order to consider whether the second dose is necessary or possibly delay it. Subject matter experts would recommend NOT administering the second dose if the ANC exceeds 5,000/mm3 (= 5.0 x 109 cells/L). These recommendations, however, are NOT included in the FDA drug label.
  • If resources are scarce, including cytokines, triage modification including when to use cytokines may be considered in order to provide the greatest good for the greatest number of people.
Key safety issues for myeloid cytokines
  • For each drug noted on this page, consult the FDA drug label for detailed information about side effects.
  • Pediatric patients <45kg
    • Neulasta pediatric dosing: As Neulasta (pegfilgrastim) is only available in a single-dose prefilled syringe and the syringe does not bear graduation marks, it is not possible to directly dose pediatric patients less than 45 kg. For pediatric patients in a hospital, the exact dose would be prepared under a laminar flow hood by hospital staff. Dosing pediatric outpatients, including during a radiological or nuclear public health emergency, currently has a risk of contamination and medication dosing errors. The FDA has received medication error reports and has requested Amgen to submit pediatric assessments as described in section 505B(a)(2)(A) of the FD&C Act, including development of an “appropriate formulation” (presentation) that can be used to administer Neulasta directly and accurately to pediatric patients who weigh less than 45 kg.
    • Stimufend (pegfilgrastim-fpgk) pediatric dosing: As there are dosing errors for Neulasta in pediatric patients less than 45 kg, Stimufend would be expected to be associated with the same type of dosing errors. The FDA has issued an order letter to Fresenius Kabi and requested to submit pediatric assessments as described in section 505B(a)(2)(A) of the FD&C Act, including development of an “appropriate formulation” (presentation) that can be used to administer Stimufend directly and accurately to pediatric patients who weight less than 45 kg.
    • Udenyca (pegfilgrastim-cbqv) pediatric dosing: As there are dosing errors for Neulasta in pediatric patients less than 45 kg, Udenyca would be expected to be associated with the same type of dosing errors. The FDA has issued an order letter to Coherus BioScience and requested to submit pediatric assessments as described in section 505B(a)(2)(A) of the FD&C Act, including development of an “appropriate formulation” (presentation) that can be used to administer Stimufend directly and accurately to pediatric patients who weight less than 45 kg.
    • Ziextenzo (pegfilgrastim-bmez) pediatric dosing: As there are dosing errors for Neulasta in pediatric patients less than 45 kg, Ziextenzo would be expected to be associated with the same type of dosing errors. The FDA has issued an order letter to Sandoz and requested to submit pediatric assessments as described in section 505B(a)(2)(A) of the FD&C Act, including development of an “appropriate formulation” (presentation) that can be used to administer Ziextenzo directly and accurately to pediatric patients who weight less than 45 kg.
  • Pregnant patients: for use of these drugs for acute exposure to myelosuppressive dose of radiation in pregnant patients
    • Experts in biodosimetry should be consulted.
    • Any pregnant patient with exposure to radiation should be evaluated by a health physicist and maternal-fetal specialist for an assessment of risk to the fetus.
    • Available data with use of Neulasta and its biosimilars (Udenyca, Stimufend, and Ziextenzo) in pregnant patients have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal studies, however, there were signs of increased embryo lethality and spontaneous abortions occurring simultaneously with signs of maternal toxicity in pregnant rabbits.
    • Although available data with use of Neulasta, Udenyca, Stimufend, and Ziextenzo in pregnant patients are insufficient to establish whether there is a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant patients exposed to filgrastim products. These studies include several observational studies of pregnancy outcomes in patients exposed to filgrastim products and have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, however, filgrastim has been shown to have adverse effects in pregnant rabbits.
    • Available data with Leukine use in pregnant patients have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, however, there were signs of increased embryo lethality and spontaneous abortion at doses that were not toxic to the mother in pregnant rabbits. Advise pregnant patients of the potential risk to a fetus.
    • Animal reproduction studies have shown an adverse effect on the fetus and/or mother and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant patients despite potential risks.
    • Advise patients of reproductive potential that Neupogen, Neulasta, Udenyca, Stimufend, Ziextenzo, Nypozi, and Leukine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Both Leukine injection (solution) and Leukine for injection (lyophilized powder) reconstituted with Bacteriostatic Water for Injection, USP contain benzyl alcohol, which has been associated with gasping syndrome in neonates and infants. The preservative benzyl alcohol can cause serious adverse reactions and death when administered intravenously to neonates and infants. If Leukine is needed during pregnancy, use only Leukine for injection (lyophilized powder) reconstituted with Sterile Water for injection without preservatives.
  • Lactation
    • Risk Summary for Neupogen and Nypozi
      • There is published literature documenting transfer of filgrastim into human milk. There are a few case reports describing the use of filgrastim in breastfeeding patients with no adverse effects noted in the infants. There are no data on the effects of filgrastim on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not absorbed orally by neonates. The developmental and health benefits of breastfeeding should be considered along with the breastfeeding parent's clinical need for Neupogen or Nypozi and any potential adverse effects on the breastfed child from Neupogen or Nypozi, or from the underlying maternal condition.
    • Risk Summary for Neulasta, Udenyca, Stimufend, and Ziextenzo
      • It is not known whether pegfilgrastim is secreted in human milk. Other recombinant G-CSF products are poorly secreted in breast milk, and G-CSF is not orally absorbed by neonates. The developmental and health benefits of breastfeeding should be considered along with the breastfeeding parent's clinical need for a pegfilgrastim product and any potential adverse effects on the breastfed child from pegfilgrastim or from the underlying maternal condition.
    • Risk Summary for Leukine
      • There is no information regarding the presence of Leukine in human milk, the effects on the breastfed child, or the effects on milk production. Administration of Leukine to rabbits during lactation resulted in reduction in postnatal offspring survival. Because of the potential for serious adverse reactions advise a lactating patient not to breastfeed during treatment and for at least 2 weeks after the last dose.
  • Patients with Sickle cell disorders:
    • Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving myeloid cytokines. Discontinue cytokine if sickle cell crisis occurs.
  • Warning and Precautions on the drug label for each product in this category should be noted. Below is a list of serious adverse effects noted on the drug labels. Most are rare. Consult drug labels for more detailed information.
    • Splenic enlargement and rupture
    • Acute Respiratory Distress Syndrome
    • Serious allergic reactions
    • Alveolar hemorrhage and hemoptysis
    • Capillary leak syndrome
    • Thrombocytopenia and leukocytosis
    • Note: bone pain, which occurs in approximately 25% of patients, is an adverse reaction, but it is not considered "serious".
Clinical Practice Guidelines for Myeloid Cytokines

See: REMM Bibliography for Acute Radiation Injury > Myeloid Cytokine Section



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Platelet Cytokine Mimetic

Key Clinical Information

  • Romiplostim (Nplate®) was approved by the FDA on January 28, 2021, as a treatment to increase survival in adult and pediatric patients (including term neonates) exposed to myelosuppressive doses of radiation, the hematopoietic subsyndrome ARS (H-ARS).
    • H-ARS is a new indication for this drug which was originally approved in 2008 for certain forms of thrombocytopenia.
    • See FDA drug label for romiplostim, revised 02/2022.
  • What is Nplate?
    • Thrombopoietin Receptor Agonist (TPO-RA)
    • Member of the TPO mimetic class, romiplostim is an Fc-peptide fusion protein (peptibody)
    • Increases platelet production through binding and activation of the TPO receptor, a mechanism analogous to endogenous TPO
    • Originally approved by the FDA in 2008 for the treatment of “thrombocytopenia in patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy”.
    • In January 2021, FDA approved romiplostim for treatment of adults and pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation.
  • What is the recommended dose of Nplate for H-ARS?
    • Dose: 10 mcg/kg administered once as a subcutaneous injection.
    • Administer the dose as soon as possible after suspected or confirmed exposure to myelosuppressive doses of radiation
    • The FDA drug label says that for treatment of myelosuppressive doses of radiation:
      • “Administer romiplostim regardless of whether a complete blood count (CBC) can be obtained.”
      • “Estimate a patient’s absorbed whole body radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.”
  • More about using Nplate for H-ARS
    • The FDA approval of Nplate for H-ARS was based on efficacy studies conducted in adult animals, accordance with FDA's animal rule.
      • Efficacy studies of Nplate could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons.
      • For this reason, the pharmacokinetics of Nplate is not available in patients acutely exposed to myelosuppressive doses of radiation.
      • The 10 mcg/kg dosing regimen for humans is based on population modeling and simulation analyses.
        • 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.
    • According to the FDA drug label…
      • “The safety of Nplate for the acute radiation syndrome setting was based on the clinical experience in patients with ITP and from a study with healthy volunteers.”
      • “The efficacy of Nplate was studied in a randomized, blinded, placebo-controlled study in a non-human primate model of radiation injury.”
        • The primary efficacy endpoint was survival.
        • Nplate significantly (one-sided p = 0.0002) increased 60-day survival in the irradiated animals: 72.5% survival (29/40) in the Nplate group compared to 32.5% survival (13/40) in the control group.
        • 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. Survival in this combined treatment group was 87.5% (95% CI: (73.2%, 95.8%)).
      • For pediatric patients (including term neonates)
        • 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.
        • A similar response to Nplate is expected in the pediatric and adult patients based on the mechanism of action of the drug and pharmacokinetics of Nplate in pediatric patients 1 year and older with ITP.
      • For pregnant patients
        • Available data with Nplate use in pregnant patients are insufficient to draw conclusions about any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, in animal reproduction and developmental toxicity studies, Nplate crossed the placenta, and adverse fetal effects included thrombocytosis, postimplantation loss, and an increase in pup mortality.
        • Advise pregnant patients of the potential risk to a fetus.
        • Advise patients of reproductive potential to inform their prescriber of a known or suspected pregnancy.
      • For lactating patients
        • There is no information regarding the presence of Nplate in human milk, the effects on the breastfed child, or the effects on milk production.
        • Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to Nplate are unknown.
        • Due to the potential for serious adverse reactions in a breastfed child from Nplate, advise lactating patients not to breastfeed during treatment with Nplate.
      • See the Nplate drug label for patient counseling information, contraindications, side effects/adverse effects/toxicities, drug interactions, and details about preparation and administration.
  • See: REMM Bibliography for Acute Radiation Injury > Platelet Cytokine Section

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