Revolade: Brand name of Eltrombopag, Thrombopoietin Receptor Agonist
Revolade (Promacta in the USA) is the trade name of the active substance Eltrombopag, an oral, small molecule thrombopoietin receptor agonist. Eltrombopag was approved in the European Union in 2010 for the treatment of chronic immune thrombocytopenia (ITP) in adults, later expanded to pediatric ITP, severe aplastic anemia (refractory or as first-line therapy combined with immunosuppression), and chronic thrombocytopenia associated with hepatitis C-related liver disease.
Revolade represents a significant innovation in hematology because it stimulates platelet production without immunosuppressive effects. This was a paradigm shift away from glucocorticoids, splenectomy, and rituximab as ITP therapy toward a targeted thrombopoietin mimetic. Romiplostim (Nplate) is a comparable active substance for subcutaneous administration, both now belong to the first or second line of therapy for chronic ITP.
Mechanism of Action
Endogenous thrombopoietin (TPO) is the most important cytokine of megakaryopoiesis and stimulates maturation and platelet production via the TPO receptor (c MPL, MPL receptor) on hematopoietic stem and progenitor cells as well as megakaryocytes. Eltrombopag binds to the transmembrane domain of the TPO receptor at a different site than TPO itself (allosteric effect), but functionally activates it.
Unlike recombinant TPO analogues, which failed in early clinical trials due to antibody formation, Eltrombopag is a synthetic small molecule with no risk of TPO antibody formation. Activation of the TPO receptor triggers JAK STAT, MAPK, and PI3K signaling cascades in megakaryocytes, leading to increased platelet formation. Initial platelet increases are measurable after approximately 1 to 2 weeks.
Pharmacokinetically, Eltrombopag is well absorbed orally (bioavailability approximately 50 percent), but absorption is significantly reduced by calcium, iron, magnesium, and aluminum in food or antacids. Half-life approximately 30 hours, elimination via bile and stool.
Indications
- Chronic immune thrombocytopenia (ITP) in adults: after inadequate response to glucocorticoids, immunoglobulins, or splenectomy
- Pediatric ITP from 1 year of age: chronic courses with persistently low platelets
- Severe aplastic anemia (SAA): as first-line therapy combined with ATG/cyclosporine (RACE study) or in refractory course
- Hepatitis C-associated chronic thrombocytopenia: to enable interferon-based antiviral therapy (less relevant today due to direct-acting antivirals)
Dosage and Administration
ITP adults: Initial dose 50 mg once daily (25 mg in East Asian descent due to elevated levels). Adjustment based on platelet count in 25 mg increments every 2 weeks, target 50,000 to 200,000/microliter. Maximum daily dose 75 mg.
Aplastic anemia: Initial dose 50 mg daily, increase up to 150 mg daily as needed, several months of therapy for hematologic response. In hepatic insufficiency: Initial dose 25 mg, slow adjustment due to reduced clearance.
Administration: on an empty stomach, at least 2 hours before or 4 hours after meals or substances containing polyvalent cations (antacids, calcium, iron). Adherence to this interval is clinically important, otherwise bioavailability decreases significantly.
Adverse Effects
Common: headaches, nausea, vomiting, diarrhea, increase in liver transaminases, fatigue, eye muscle and vision disorders, peripheral edema, myalgia.
Serious: hepatotoxicity up to hepatocellular damage, thromboembolic events (pulmonary embolism, deep vein thrombosis, especially when platelets exceed target), cataract formation with long-term use, bone marrow fibrosis (reticulin fiber formation) with long-term therapy, hemorrhagic events upon abrupt discontinuation with platelet rebound downward.
Important: Patients require regular blood counts and liver transaminases, at least monthly in the initial phase. Upon signs of hepatotoxicity (jaundice, dark urine, abdominal pain), immediate monitoring and therapy adjustment.
Drug Interactions
- Polyvalent cations (calcium, magnesium, aluminum, iron, zinc) in antacids, multivitamins, or food: significant reduction of Eltrombopag absorption through chelate formation, administer with 2 to 4 hour separation
- Statins (rosuvastatin): increased statin levels through Eltrombopag, halve dose or switch statin
- Lopinavir/ritonavir and other CYP/UGT modulating HIV therapies: level changes possible
- Cyclosporine: reduced Eltrombopag levels, consider dose adjustment
- Methotrexate, topotecan, irinotecan, and other OATP1B1 substrates: increased levels possible
Special Precautions
Pregnancy and lactation: limited data in pregnancy. If used, safe contraception should be used during and for at least 7 days after therapy completion. Not recommended during breastfeeding.
Before therapy initiation: liver transaminases, bilirubin, creatinine, blood count as baseline values, eye examination recommended due to cataract risk.
Monitoring: platelets weekly until stable, then monthly. Liver transaminases every 2 weeks during dose escalation, then monthly. If platelets exceed 200,000/microliter, dose reduction, if platelets exceed 400,000/microliter, therapy interruption due to thrombosis risk.
Discontinuation: Eltrombopag must be gradually reduced, abrupt discontinuation can lead to rebound thrombocytopenia with bleeding risk. Regular platelet monitoring for at least 4 weeks after therapy completion.
You Might Also Be Interested In
- Romiplostim, subcutaneous TPO receptor agonist
- Rituximab, anti-CD20 antibody in refractory ITP
- Dexamethasone, glucocorticoid in ITP initial therapy
- Cyclosporine, immunosuppressive in aplastic anemia
- Heparin, anticoagulation in complications
Frequently Asked Questions
What is Revolade and what is Eltrombopag?
Revolade is the trade name of Novartis (Promacta in the USA), Eltrombopag is the active substance. Both refer to the same medication. Generics are already available in some countries.
Why can't I take dairy products or iron before and after Revolade?
Calcium, magnesium, iron, and aluminum form chelates with Eltrombopag that are not absorbed. Bioavailability can decrease by up to 70 percent. Therefore, a separation of at least 2 hours before and 4 hours after each dose of antacids, dairy products, multivitamins with minerals, or iron supplements is mandatory.
How quickly will my platelets rise?
Initial platelet increases are usually measurable after 1 to 2 weeks, maximum response occurs after 4 to 6 weeks. In aplastic anemia, hematologic response can take several months. Regular platelet monitoring is important for dose adjustment.
What should I do at the end of therapy?
Eltrombopag is typically taken long-term or permanently, because platelets usually fall again after discontinuation. With clinical remission, a trial discontinuation can be attempted under close platelet monitoring. Gradual dose reduction is standard, abrupt discontinuation increases bleeding risk.
Sources
- EMA, Revolade (Eltrombopag) EPAR
- DGHO Onkopedia, Immune Thrombocytopenia
- Gelbe Liste, Eltrombopag Active Substance Profile
- BfArM, Federal Institute for Drugs and Medical Devices
Legal Notice and Disclaimer
The information provided on this page is for general informational purposes only and does not constitute medical advice, diagnosis, or treatment recommendation. It does not replace the advice of a licensed physician or pharmacist. Medications should only be taken upon medical prescription or pharmaceutical dispensing. All information is based on expert information published at the time of creation and recognized scientific sources; the current package insert of the manufacturer is always authoritative. Sanoliste assumes no liability for completeness, timeliness, or accuracy of the information presented. In a medical emergency, call the emergency number 112.