Nplate

Thrombopoietin (TPO) Receptor Agonists

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Romiplostim should be clear and colorless.[34386]

Reconstitution
For doses 23 mcg and more: Reconstitute with Sterile Water for Injection; dilution is not required.
Dilute the 125 mcg vial (total vial content, 230 mcg) with 0.44 mL of Sterile Water for Injection (final concentration of 500 mcg/mL).
Dilute the 250 mcg vial (total vial content, 375 mcg) with 0.72 mL of Sterile Water for Injection (final concentration of 500 mcg/mL).
Dilute the 500 mcg vial (total vial content, 625 mcg) with 1.2 mL of Sterile Water for Injection (final concentration of 500 mcg/mL).
For doses less than 23 mcg: Reconstitute with Sterile Water for Injection, then dilute with 0.9% Sodium Chloride Injection.
Dilute the 125 mcg vial (total vial content, 230 mcg) with 0.44 mL of Sterile Water for Injection. Additional dilution with 1.38 mL of 0.9% Sodium Chloride Injection is required (final concentration of 125 mcg/mL).
Dilute the 250 mcg vial (total vial content, 375 mcg) with 0.72 mL of Sterile Water for Injection. Additional dilution with 2.25 mL of 0.9% Sodium Chloride Injection is required (final concentration of 125 mcg/mL).
Dilute the 500 mcg vial (total vial content, 625 mcg) with 1.2 mL of Sterile Water for Injection. Additional dilution with 3.75 mL of 0.9% Sodium Chloride Injection is required (final concentration of 125 mcg/mL).
Gently swirl and invert the vial. Do not shake. Dissolution should occur within 2 minutes.
Do not pool unused portions from vials or administer more than 1 dose from a vial.
Storage: Protect from light. Product reconstituted with Sterile Water for Injection and not further diluted can remain in the original vial at room temperature or refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours, or held in a syringe at room temperature for up to 4 hours. Reconstituted product further diluted with Sodium Chloride Injection can be held in a syringe at room temperature or in the original vial refrigerated for no longer than 4 hours prior to administration.[34386]
Subcutaneous Injection
Overdoses have been reported due to medication errors. Withdraw the appropriate volume from the vial.
Administer only in a syringe with 0.01 mL graduations, and verify that the syringe contains the correct dosage.[34386]
Inject romiplostim subcutaneously into the outer aspect of the upper arm, abdomen (except for 2 inches around the navel), or front aspect of the middle thighs. Do not inject into an area that has scars or stretch marks or is tender, red, bruised, or hard. Rotate injection sites.

headache / Early / 21.0-21.0
thromboembolism / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

antibody formation / Delayed / 1.0-10.0
peripheral edema / Delayed / 7.0-7.0
thrombocytosis / Delayed / 2.0-2.0
thrombocytopenia / Delayed / Incidence not known

infection / Delayed / 5.0-31.0
arthralgia / Delayed / 26.0-26.0
fever / Early / 24.0-24.0
diarrhea / Early / 20.0-20.0
dizziness / Early / 17.0-17.0
insomnia / Early / 16.0-16.0
rash / Early / 15.0-15.0
myalgia / Early / 14.0-14.0
abdominal pain / Early / 11.0-14.0
dyspepsia / Early / 7.0-7.0
purpura / Delayed / 7.0-7.0
paresthesias / Delayed / 6.0-6.0
sinusitis / Delayed / 5.0-5.0
urticaria / Rapid / 5.0-5.0
nausea / Early / 5.0
cough / Delayed / 5.0
vomiting / Early / 5.0

Nplate

Rx

Parenteral thrombopoietin receptor agonist
Used for treatment of immune thrombocytopenia and hematopoietic syndrome of acute radiation syndrome
Not to be used to normalize platelet counts

1 mcg/kg/week subcutaneously initially; adjust dose based on platelet counts only. Adjust dose in 1 mcg/kg/week increments to achieve a platelet count of 50,000/mm3 or more. Median effective dose: 2 mcg/kg/week. Max: 10 mcg/kg/week. Monitor CBC weekly during the dose adjustment phase and then monthly thereafter. Use the lowest dose needed. If the platelet count is less than 50,000/mm3, increase the dose by 1 mcg/kg/week. If the platelet count is more than 200,000/mm3 for 2 consecutive weeks, reduce the dose by 1 mcg/kg/week. If the platelet count is more than 400,000/mm3, temporarily withhold treatment and monitor the platelet count weekly; resume at a dose reduced by 1 mcg/kg/week after the platelet count is less than 200,000/mm3. Discontinue romiplostim if the platelet count does not increase to a level sufficient to avoid clinically significant bleeding after 4 weeks at the maximum dose of 10 mcg/kg/week. Monitor CBC weekly for at least 2 weeks after discontinuation.[34386]

1 mcg/kg/week subcutaneously initially; adjust dose based on platelet counts and changes in body weight. Adjust dose in 1 mcg/kg/week increments to achieve a platelet count of 50,000/mm3 or more. Median effective dose: 5.5 mcg/kg/week. Max: 10 mcg/kg/week. Monitor CBC weekly during the dose adjustment phase and then monthly thereafter. Reassess weight every 12 weeks. Use the lowest dose needed. If the platelet count is less than 50,000/mm3, increase the dose by 1 mcg/kg/week. If the platelet count is more than 200,000/mm3 for 2 consecutive weeks, reduce the dose by 1 mcg/kg/week. If the platelet count is more than 400,000/mm3, temporarily withhold treatment and monitor the platelet count weekly; resume at a dose reduced by 1 mcg/kg/week after the platelet count is less than 200,000/mm3. Discontinue romiplostim if the platelet count does not increase to a level sufficient to avoid clinically significant bleeding after 4 weeks at the maximum dose of 10 mcg/kg/week. Monitor CBC weekly for at least 2 weeks after discontinuation.[34386]

10 mcg/kg subcutaneously once, as soon as possible after suspected or confirmed exposure to radiation concentrations more than 2 gray.

10 mcg/kg subcutaneously once, as soon as possible after suspected or confirmed exposure to radiation concentrations more than 2 gray.

10 mcg/kg subcutaneously once, as soon as possible after suspected or confirmed exposure to radiation concentrations more than 2 gray.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Romiplostim products.

Nplate/Romiplostim Subcutaneous Inj Pwd F/Sol: 125mcg, 250mcg, 500mcg

10 mcg/kg/week subcutaneously.

10 mcg/kg/week subcutaneously.

10 mcg/kg/week subcutaneously.

10 mcg/kg/week subcutaneously.

10 mcg/kg subcutaneously once for hematopoietic syndrome.

10 mcg/kg subcutaneously once for hematopoietic syndrome.

Romiplostim is a thrombopoietin-mimetic Fc-peptide fusion protein (peptibody) produced by recombinant DNA technology in Escherichia coli. Romiplostim shares no amino acid sequence homology with endogenous thrombopoietin (TPO) and therefore is not expected to elicit cross-reacting antibodies that cause thrombocytopenia, a problem that has occurred with previously studied recombinant TPO agents. The peptibody molecule contains 2 identical single-chain subunits, each consisting of human immunoglobulin IgG1 Fc domain (constant region), covalently linked at the C-terminus to 2 identical peptide sequences that each bind and activate the TPO receptor. The Fc component of the romiplostim peptibody extends the half-life, allowing it to remain active in the circulation much longer than endogenous TPO; it is eventually removed by the reticuloendothelial system.
 
In vitro, romiplostim binds to the TPO receptor (also known as cMpl), which consists of 2 cytokine receptor modules (CRMs). Romiplostim binds to the distal CRM, allowing the cMpl receptor to become active. As a result of this, romiplostim induces phosphorylation of JAK2 and STAT5 in TPO-dependent cell lines, promotes growth of TPO-dependent cell lines and megakaryocyte-colony forming cells, and increases megakaryocyte ploidy and maturation.[34387] Increased megakaryocyte production may lead to bone marrow reticulin deposition as transforming growth-factor beta (TGF-beta) is released from megakaryocytes. TGF-beta has previously been shown to increase reticulin fiber formation.[34388] Elimination of romiplostim is platelet-dependent; increased platelet counts will cause decreased serum concentrations of romiplostim.

Romiplostim is administered subcutaneously. Elimination is partially dependent on the thrombopoietin (TPO) receptor on platelets. Half-life ranges from 1 to 34 days (median: 3.5 days). No accumulation in serum concentrations (n = 4) was observed after 6 weekly doses of 3 mcg/kg.[34386]

Peak serum concentrations are observed approximately 7 to 50 hours (median: 14 hours) after administration. Romiplostim displays dose-dependent increases in platelets. After a single dose of 1 to 10 mcg/kg in patients with chronic immune thrombocytopenic purpura (ITP), platelet counts were 1.3 to 14.9 times higher than baseline over a 2 to 3 week period. Patients with higher platelet counts exhibit lower serum concentrations of romiplostim, and patients with lower platelet counts exhibit higher serum concentrations of romiplostim. Serum concentrations of romiplostim do not correlate with doses administered.[34386]

Romiplostim may cause fetal harm when administered during human pregnancy. Limited data in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction and developmental toxicity studies, romiplostim crossed the placenta; adverse fetal effects included thrombocytosis, postimplantation loss, and an increase in pup mortality. Women who become pregnant during romiplostim treatment should enroll in the manufacturer's pregnancy surveillance program by calling 1-800-772-6432.[34386]

Advise women to avoid breast-feeding during treatment with romiplostim, due to the potential for serious adverse reactions. There is no information regarding the presence of romiplostim in human milk, the effects on the breastfed child, or the effects on milk product. Human IgG is present in human milk, but published data suggest breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.[34386]