Romiplostim

Romiplostim

Systematic (IUPAC) name
L-methionyl[human immunogloblin heavy constant gamma 1-(227 C-terminal residues)-peptide (Fc fragment)] fusion protein with 41 amino acids peptide, (7-7′:10,10′)-bisdisulfide dimer
Clinical data
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a609008
Licence data	US FDA:link
Pregnancy category	US: C (Risk not ruled out)
Legal status	US: ℞-only
Routes of administration	Subcutaneous injection
Pharmacokinetic data
Biological half-life	1 to 34 days
Identifiers
CAS Number	267639-76-9 N
ATC code	B02BX04 (WHO)
IUPHAR/BPS	6974
UNII	GN5XU2DXKV Y
ChEMBL	CHEMBL1201832 N
Chemical data
Formula	C2634H4086N722O790S18
Molecular mass	59 kDa
NY (what is this?)  (verify)

Romiplostim (rINN, USAN) is a fusion protein analog of thrombopoietin, a hormone that regulates platelet production.

Safety Concerns vs. Marketing

The drug was developed by Amgen and is marketed under the trade name Nplate through a restricted usage program called NEXUS. During development and clinical trials the drug was called AMG531.

Romiplostim is indicated as a potential treatment for chronic idiopathic (immune) thrombocytopenic purpura (ITP). Romiplostim was designated an orphan drug by the U.S. Food and Drug Administration (FDA) in 2003, as the chronic ITP population in the USA is under 200,000 (the chronic adult ITP population in the USA is thought to be around 60,000, with women outnumbering men by a factor of two). The wholesale cost of romiplostim if administered weekly is currently estimated at US $55,250 per year.

On August 22, 2008, the FDA approved romiplostim as a long-term treatment for chronic ITP in adults who have not responded to other treatments, such as corticosteroids, intravenous immunoglobulin, Rho(D) immune globulin or splenectomy.

Treatment regimen

Romiplostim treatment is generally administered at weekly intervals via subcutaneous injection. Prior to injection, a complete blood count (CBC) is obtained, as the dosage is dependent on the individual's body weight and platelet count at the time of treatment. The goal of treatment is to maintain the count above 50,000 per cubic millimeter (mm³) of blood, not to achieve a normal count—defined as 150,000–450,000 per mm³ in most healthy individuals. If a count of 200,000 or higher is achieved for two consecutive weeks a reduced dose is administered or treatment is suspended until the count decreases below 200,000. Discontinuation of romiplostim must be approached with great caution, as a rapid decrease in the platelet count may occur, possibly leading to bleeding diathesis.

Clinical efficacy

In well designed, 24-week, Phase III trials, romiplostim was significantly more effective than placebo in achieving the primary endpoint of a protocol-defined durable platelet response in nonsplenectomized or splenectomized adults with chronic immune thrombocytopenic purpura.

Side-effects

Romiplostim's effect is to stimulate the patient's megakaryocytes to produce platelets at a more rapid than normal rate, thus overwhelming the immune system's ability to destroy them. As doing so involves changes to the bone marrow chemistry, a number of potentially serious side-effects may develop, including death, myalgia, joint and extremity discomfort, insomnia, thrombocytosis, which may lead to potentially fatal clots, and bone marrow fibrosis, the latter which may result in an unsafe decrease in the red blood count.

External links

• Nplate
• Nplate full prescribing information