Done by : Ahmed Fahad Basilim clinical pharmacist intern Supervised by: Dr. Muna Filfilan

Nplate ™ - Romiplostim

- Manufacturer: Amgen, Inc. - FDA Approval Date: 08/2008 Nplate ™ - Romiplostim

- What is Nplate? Nplate ™ - Romiplostim

- What is Nplate? Nplate is a man-made protein medicine used to treat low blood platelet counts in adults. Romiplostim is produced by recombinant DNA technology in Escherichia coli (E coli).Escherichia coli - Mechanism of Action: Nplate ™ - Romiplostim

- What is Nplate? Nplate is a man-made protein medicine used to treat low blood platelet counts in adults. Romiplostim is produced by recombinant DNA technology in Escherichia coli (E coli). Escherichia coli Mechanism of Action: Is an antihemorrhagic. This member of the thrombopoietin mimetic class is an Fc-peptide fusion protein (peptibody) that activates intracellular transcriptional pathways leading to increased platelet production via the thrombopoietin receptor. Nplate ™ - Romiplostim

- Indication: Thrombocytopenia in patients with chronic immune thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Nplate ™ - Romiplostim - Indication: Thrombocytopenia in patients with chronic immune thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. - Place in therapy: Treat ITP in patients with PLT <50,000 despite above therapies.

Nplate ™ - Romiplostim - Indication: Thrombocytopenia in patients with chronic immune thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. - Place in therapy: Treat ITP in patients with PLT <50,000 despite above therapies. - Nplate should not be used in an attempt to normalize platelet counts.

- Pharmacokinetics: - Peak: 7 to 50 hr (median 14 hr) - t 1/2 :1-34 days (median 3.5 days) Nplate ™ - Romiplostim

- Dosing: -Initial: 1 mcg/kg SQ weekly based on TBW - Increase by 1 mcg/kg until PLT > 50, If PLT > 200,000 for 2 weeks, ↓ by 1 mcg/kg. - If PLT > 400,000, hold. After PLT < 200,000 resume at dose ↓ by 1 mcg/kg. - Average dose: 2 mcg/kg/wk - Max dose: 10 mcg/kg/wk Nplate ™ - Romiplostim

- Discontinuation: - 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, Obtain CBCs, including platelet counts, weekly for at least 2 weeks following discontinuation of Nplate. Nplate ™ - Romiplostim

-Efficacy Monitoring: - Monitor CBCs, including platelet counts and peripheral blood smears, weekly until a stable Nplate dose has been achieved. - Thereafter, monitor CBCs, including platelet counts and peripheral blood smears, at least monthly.

Nplate ™ - Romiplostim - Common Adverse Effects : RomiplostimPlacebo Headache35%32% Arthralgia26%20% Dizziness17%0% Insomnia16%7% Myalgia14%2% Pain in extremity13%5% Abdominal pain11%0% Shoulder pain8%0% Dyspepsia7%0% Paresthesia6%0%

Nplate ™ - Romiplostim - Immunogenicity: As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein. Patients were screened for immunogenicity to romiplostim using a BIAcore-based biosensor immunoassay. This assay is capable of detecting both high- and low-affinity binding antibodies that bind to romiplostim and cross-react with TPO.

Nplate ™ - Romiplostim - Serious Adverse Effects: -Bone marrow reticulin deposition - Romiplostim: 4%, Placebo 0% - Worsening thrombocytopenia after discontinuation - Romiplostim: 7%, Placebo 0%

Nplate ™ - Romiplostim - Contraindications: - None listed - Warnings: - Risk for bone marrow fibrosis - Hematologic malignancies - Thromboembolism - Lack of response: determine cause - Precautions: - Hepatic impairment - Renal impairment - Pediatrics

Nplate ™ - Romiplostim -Drug Interactions: - No formal studies conducted.

Nplate ™ - Romiplostim - Drug Facts: - Romiplostim is a novel thrombopoietin peptide mimetic which increases platelet production by binding to and activating the thrombopoietin receptor. - The platelet count will increase in 4-9 days and peaks in days.

Nplate ™ - Romiplostim - Summary: - There are limited FDA approved treatments (i.e., corticosteroids, immunglobulins) or surgical therapy (removal of the spleen) for adult patients with chronic ITP.

Nplate ™ - Romiplostim - Summary: - There are limited FDA approved treatments (i.e., corticosteroids, immunglobulins) or surgical therapy (removal of the spleen) for adult patients with chronic ITP. - Nplate is first and only available agent which treats ITP by increasing platelet production through activation of the thrombopoietin receptor.

Nplate ™ - Romiplostim - Summary: - Romiplostim is not intended to normalize platelet counts. It should be titrated weekly by 1mcg/kg to achieve platelet count ≥ 50,000 as necessary to reduce bleeding risk. Monitoring CBC, platelet counts, and peripheral blood smear is essential.

Nplate ™ - Romiplostim - Summary: - Romiplostim is not intended to normalize platelet counts. It should be titrated weekly by 1mcg/kg to achieve platelet count ≥ 50,000 as necessary to reduce bleeding risk. Monitoring CBC, platelet counts, and peripheral blood smear is essential. - May cause rare but serious adverse effects: bone marrow reticulin formation, thromboembolism, hematologic malignancies or worsened platelet counts after cessation of therapy.

Nplate ™ - Romiplostim -References: -