From the Guidelines
The FDA-approved drugs used to stimulate megakaryocytes to produce platelets are primarily thrombopoietin receptor agonists, with romiplostim (Nplate) and eltrombopag (Promacta) being the most commonly used options, as supported by the most recent study 1.
Key Points
- Romiplostim is typically administered as a weekly subcutaneous injection, with the dose adjusted based on platelet response, usually starting at 1 mcg/kg.
- Eltrombopag is an oral medication taken daily, with a starting dose of 50 mg, which can be adjusted based on platelet counts.
- These drugs work by binding to and activating the thrombopoietin receptor on megakaryocytes, stimulating their growth and differentiation, which leads to increased platelet production.
- Treatment duration varies depending on the underlying condition and individual response, but it's often long-term for chronic conditions.
- Regular monitoring of platelet counts is essential to adjust dosing and prevent excessive platelet production.
Mechanism of Action and Efficacy
The mechanism of action of TPO-RAs involves agonistic activity on the thrombopoietin receptor, which in turn triggers an increase of megakaryopoiesis and platelet production 1. In clinical trials, TPO-RAs have been shown to be highly effective, with initial responses observed already after 1–2 weeks of treatment, while significantly reducing bleeding events and emergency hospitalizations 1.
Safety and Tolerability
TPO-RAs are well tolerated, especially in the long-term, and are not linked to increased thrombotic risk, although the correlation between TPO-RA usage and thrombotic risk is still under debate 1. The long-term use of TPO-RAs does not affect bone marrow tolerability, and the introduction of TPO-RAs has a positive impact on the quality of life of ITP patients 1.
Clinical Use
These medications are primarily used in conditions like chronic immune thrombocytopenia (ITP) or thrombocytopenia associated with certain bone marrow disorders. It's essential to note that while effective, these drugs do not address the underlying cause of thrombocytopenia and may have potential side effects, including an increased risk of blood clots 1.
From the FDA Drug Label
Eltrombopag is a TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor (also known as cMpl) and initiates signaling cascades that induce proliferation and differentiation of megakaryocytes leading to increased platelet production. Romiplostim is a thrombopoietin receptor agonist (TPO-RA). Romiplostim, a member of the TPO mimetic class, is an Fc-peptide fusion protein (peptibody). Nplate increases platelet production through binding and activation of the TPO receptor, a mechanism analogous to endogenous TPO.
The FDA-approved drugs used to stimulate megakaryocytes to produce platelets are:
- Romiplostim (Nplate), a thrombopoietin receptor agonist (TPO-RA) 2
- Eltrombopag, a TPO-receptor agonist 3
From the Research
FDA Approved Drugs for Stimulating Megakaryocytes
The following FDA approved drugs are used to stimulate megakaryocytes to produce platelets:
- Romiplostim
- Eltrombopag
- Avatrombopag
- Lusutrombopag
Mechanism of Action
These drugs, known as thrombopoietin receptor agonists (TPO-RAs), work by stimulating the TPO receptor on hematopoietic stem cells, megakaryocytes, and megakaryocyte precursor cells, resulting in increased platelet production 4, 5, 6, 7, 8.
Indications
The current indications for these TPO-RAs include:
- Treatment of chronic immune thrombocytopenia (ITP) in cases of insufficient response to prior treatment (avatrombopag, eltrombopag, romiplostim)
- Management of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure (avatrombopag, lusutrombopag)
- Management of severe aplastic anemia (eltrombopag)
- Management of thrombocytopenia associated with interferon-based therapy for hepatitis C (eltrombopag) 4, 7.