| Primary information |
|---|
| ID | 1640 |
| ThPP ID | Th1145 |
| Therapeutic Peptide/Protein Name | Romiplostim |
| Sequence | MDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 59000 |
| Chemical Formula | C2634H4086N722O790S18 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Immunen thrombocytopenia patients, subQ = 3.5 days (median) (range 1-34 days) |
| Description | Romiplostim is a thrombopoiesis stimulating dimer Fc-peptide fusion protein (peptibody) to increase platelet production through activation of the thrombopoietin receptor. The peptibody molecule has two identical single-chain subunits, each one is made up of 269 amino acid residues. Each subunit consists of an IgG1 Fc carrier domain that is covalently attached to a polypeptide sequence that contains two binding domains to interact with thrombopoietin receptor c-Mpl. Each domain consists of 14 amino acids. Interestingly, romiplostim's amino acid sequence is not similar to that of endogenous thrombopoietin. Romiplostim is produced by recombinant DNA technology in Escherichia coli. FDA approved on August 22, 2008. |
| Indication/Disease | Treatment of chronic immune thrombocytopenic purpura. |
| Pharmacodynamics | Responses to platelet increase varies between patients thus indicating a need for individualization of dose. However, a dose dependent-increase in platelet counts have been observed in clinical trials. Does not affect platelet destruction. |
| Mechanism of Action | Romiplostim is a thrombopoietin receptor agonist that activates intracellular transcriptional pathways via c-Mpl to increase production of platelets. It also works similarly to thrombopoietin (TPO), an endogenous glycoprotein hormone that regulates the production of platelets in the bone marrow. |
| Toxicity | The most common adverse reactions ( higher patient incidence in Nplate versus placebo) are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, and paresthesia. Headache was the most commonly reported adverse reaction that did not occur at higher patient incidence in Nplate versus placebo. LD50 = 980 mg/kg. |
| Metabolism | N.A. |
| Absorption | Cmax, healthy volunteers, subQ = 24-36 hours; Cmax, immune thrombocytopenia patients, subQ = 7-50 hours (median = 14 hours); Not affected by age, weight, or gender. Accumulation does not occur after six weekly doses of 3 mcg/kg romiplostim. |
| Volume of Distribution | romiplostim indicates saturation of c-Mpl receptors.Vd, 0.3 microg/kg = 122 mL/kgVd, 10 microg/kg = 48.2 mL/kg |
| Clearance | Renal clearance (more dominant mode of clearance as dose increases) and binding to c-Mpl receptors (dominant mode of clearance at low doses) |
| Categories | Colony-Stimulating Factors and Thrombopoietic Agents |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | N.A. |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Nplate |
| Company | Amgen |
| Brand Discription | Romiplostim, a member of the TPO mimetic class, is an Fc-peptide fusion protein (peptibody) that activates intracellular transcriptional pathways leading to increased platelet production via the TPO receptor (also known as cMpl). The peptibody molecule contains two identical single-chain subunits, each consisting of human immunoglobulin IgG1 Fc domain, covalently linked at the C-terminus to a peptide containing two thrombopoietin receptor-binding domains. Romiplostim has no amino acid sequence homology to endogenous TPO. Romiplostim is produced by recombinant DNA technology in Escherichia coli (E coli). |
| Prescribed for | Nplate is indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. |
| Chemical Name | N.A. |
| Formulation | 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. Each single-use 250 mcg vial of Nplate contains the following: 375 mcg romiplostim, 30 mg mannitol, 15 mg sucrose, 1.2 mg L-histidine, 0.03 mg polysorbate 20, and sufficient HCl to adjust the pH to a target of 5.0. Each single-use 500 mcg vial of Nplate contains the following: 625 mcg romiplostim, 50 mg mannitol, 25 mg sucrose, 1.9 mg L-histidine, 0.05 mg polysorbate 20, and sufficient HCl to adjust the pH to a target of 5.0 |
| Physcial Appearance | Sterile, preservative-free, lyophilized, solid white powder |
| Route of Administration | Subcutaneous Injection |
| Recommended Dosage | Use the lowest dose of Nplate to achieve and maintain a platelet count ≥ 50 x 109/L as necessary to reduce the risk for bleeding. Administer Nplate as a weekly subcutaneous injection with dose adjustments based upon the platelet count response. The prescribed Nplate dose may consist of a very small volume (eg, 0.15 mL). Administer Nplate only with a syringe that contains 0.01 mL graduations. The initial dose for Nplate is 1 mcg/kg based on actual body weight. Dose AdjustmentsUse the actual body weight at initiation of therapy, then adjust the weekly dose of Nplate by increments of 1 mcg/kg until the patient achieves a platelet count ≥ 50 x 109/L as necessary to reduce the risk for bleeding; do not exceed a maximum weekly dose of 10 mcg/kg. In clinical studies, most patients who responded to Nplate achieved and maintained platelet counts ≥ 50 x 109/L with a median dose of 2 mcg/kg. During Nplate therapy, assess CBCs, including platelet counts, weekly until a stable platelet count ( ≥ 50 x 109/L for at least 4 weeks without dose adjustment) has been achieved. Obtain CBCs, including platelet counts, monthly thereafter. |
| Contraindication | N.A. |
| Side Effects | The following serious adverse reactions: Progression of Myelodysplastic Syndromes, Thrombotic/Thromboembolic Complications, Loss of Response to Nplate, Overdoses due to medication errors have been reported in patients receiving Nplate. In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications. In this case, discontinue Nplate and monitor platelet counts. Reinitiate treatment with Nplate in accordance with dosing and administration recommendations. |
| Useful Link | http://www.rxlist.com/nplate-drug.htm http://www.nplate.com/patient/how-nplate-may-help/how-nplate-works.html https://en.wikipedia.org/wiki/Romiplostim http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088667.pdf |
| PubMed ID | 22316355 |
| 3-D Structure | N.A. |