Eltrombopag 12.5mg Tablets
WARNING: Severe and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems like dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.This drug may raise the risk of liver failure when taken with interferon and ribavirin in patients with hepatitis C. If your doctor tells you to stop taking interferon and ribavirin, you will also need to stop taking this drug. @ COMMON USES: It is used to raise platelet counts.It is used to treat immune thrombocytopenia (ITP).It is used to treat aplastic anemia.
Drug Class
Thrombopoietin Receptor Agonist
Pharmacologic Class
Thrombopoietin Receptor Agonist
Pregnancy Category
Category C
FDA Approved
Nov 2008
DEA Schedule
Not Controlled
Overview
What is this medicine?
Eltrombopag is a medication used to help your body make more platelets, which are blood cells that help stop bleeding. It works by stimulating a natural process in your bone marrow. It's used for conditions where you have low platelet counts, like certain types of immune thrombocytopenia (ITP), severe aplastic anemia, or low platelets due to Hepatitis C.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Take your medication either on an empty stomach or with a meal that is low in calcium.
If you are taking other medications, you may need to take this medication at a different time to avoid interactions. To minimize interactions, take your medication at least 2 hours before or 4 hours after consuming foods or drinks that are high in calcium, such as dairy products, certain fruits, vegetables, and juices. Also, avoid taking your medication at the same time as antacids or products that contain calcium, iron, aluminum, magnesium, selenium, or zinc.
Important Administration Instructions
Swallow your medication whole; do not chew, break, or crush it.
Do not mix your medication with food or drinks.
Storing and Disposing of Your Medication
Store your medication in its original container at room temperature, in a dry place. Avoid storing it in a bathroom.
What to Do If You Miss a Dose
If you miss a dose, skip it and return to your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed dose.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and follow the instructions closely. Take your medication either on an empty stomach or with a meal that is low in calcium.
If you are taking other medications, you may need to take this medication at a different time to avoid interactions. To minimize interactions, take your medication at least 2 hours before or 4 hours after consuming foods or drinks that are high in calcium, such as dairy products, certain fruits, vegetables, and juices. Also, avoid taking your medication at the same time as antacids or products that contain calcium, iron, aluminum, magnesium, selenium, or zinc.
Important Administration Instructions
Swallow your medication whole; do not chew, break, or crush it.
Do not mix your medication with food or drinks.
Storing and Disposing of Your Medication
Store your medication in its original container at room temperature, in a dry place. Avoid storing it in a bathroom.
What to Do If You Miss a Dose
If you miss a dose, skip it and return to your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed dose.
Lifestyle & Tips
- Take eltrombopag on an empty stomach, at least 2 hours before or 4 hours after any food, dairy products, antacids, or mineral supplements (like iron, calcium, magnesium, aluminum, selenium, zinc). These can prevent the medicine from being absorbed properly.
- Do not crush or chew tablets; swallow whole.
- Do not stop taking eltrombopag without talking to your doctor, as your platelet count may drop significantly.
- Avoid grapefruit and grapefruit juice as they may affect metabolism.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Varies by indication and patient factors (e.g., ancestry, hepatic impairment). Initial doses typically range from 25 mg to 50 mg once daily. Titrate to achieve target platelet count.
Dose Range:
12.5 - 150 mg
Condition-Specific Dosing:
Chronic Immune Thrombocytopenia (ITP):
Initial 50 mg once daily (25 mg for patients of East Asian ancestry). Adjust dose to achieve and maintain platelet count âĨ50,000/mcL. Max 150 mg/day.
Severe Aplastic Anemia (SAA):
Initial 50 mg once daily. Titrate up to 150 mg/day based on platelet response and tolerability.
Chronic Hepatitis C (HCV)-related Thrombocytopenia:
Initial 25 mg once daily. Titrate to achieve platelet count required for antiviral therapy. Max 100 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established (approved for ITP in patients âĨ1 year of age)
Child:
ITP (âĨ1 year): Initial 25 mg once daily (12.5 mg for patients of East Asian ancestry). SAA (âĨ2 years): Initial 25 mg once daily. Titrate based on response.
Adolescent:
ITP (âĨ1 year): Initial 25 mg once daily (12.5 mg for patients of East Asian ancestry). SAA (âĨ2 years): Initial 25 mg once daily. Titrate based on response.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
No dose adjustment required.
Dialysis:
No specific recommendations; monitor closely.
Hepatic Impairment:
Mild:
No initial dose adjustment for SAA. For ITP/HCV, consider starting at 25 mg once daily.
Moderate:
For ITP/HCV, reduce initial dose to 25 mg once daily. For SAA, no initial dose adjustment, but monitor closely.
Severe:
For ITP/HCV, reduce initial dose to 12.5 mg once daily. For SAA, no initial dose adjustment, but monitor closely.
Confidence:
High
Pharmacology
Mechanism of Action
Eltrombopag is a non-peptide thrombopoietin (TPO) receptor agonist. It interacts with the transmembrane domain of the human TPO receptor and initiates signaling cascades that lead to the proliferation and differentiation of megakaryocytes from bone marrow progenitor cells, resulting in increased platelet production.
Pharmacokinetics
Absorption:
Bioavailability:
Tablet: ~31% (solution: ~39-52%)
Tmax:
2-6 hours
FoodEffect:
High-fat, high-calorie meals significantly decrease AUC. Polyvalent cations (e.g., calcium, iron, magnesium, aluminum, selenium, zinc) significantly chelate eltrombopag, reducing absorption. Must be taken at least 2 hours before or 4 hours after products containing polyvalent cations.
Distribution:
Vd:
~10 L/kg
ProteinBinding:
>99%
CnssPenetration:
Limited
Elimination:
HalfLife:
21-32 hours
Clearance:
Not readily available as a single value, but primarily hepatic metabolism and biliary excretion.
ExcretionRoute:
Feces (59%), Urine (31%)
Unchanged:
<1% in urine
Pharmacodynamics
OnsetOfAction:
Platelet count increase typically observed within 1-2 weeks.
PeakEffect:
Peak platelet response usually achieved within 2-4 weeks of dose titration.
DurationOfAction:
Platelet counts typically return to baseline within 1-2 weeks after discontinuation.
Safety & Warnings
BLACK BOX WARNING
Hepatotoxicity: Eltrombopag can cause hepatotoxicity. Measure serum ALT, AST, and bilirubin prior to initiation of eltrombopag, every 2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose. Discontinue eltrombopag if liver enzyme abnormalities persist or worsen. Risk of Thrombosis/Thromboembolism: Thrombotic/thromboembolic complications may occur, particularly in patients with chronic liver disease.
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of a urinary tract infection (UTI), including:
+ Blood in the urine
+ Burning or pain when passing urine
+ Frequent or urgent need to urinate
+ Fever
+ Lower stomach pain
+ Pelvic pain
Neurological symptoms, such as:
+ Weakness on one side of the body
+ Trouble speaking or thinking
+ Change in balance
+ Drooping on one side of the face
+ Blurred eyesight
Vision changes, including:
+ Change in eyesight
+ Eye pain
+ Severe eye irritation
Unusual bruising or bleeding while taking this medication or after stopping it
Confusion
Abdominal swelling
Swelling in the arms or legs
Fever or chills
Signs of a blood clot, such as:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, change of color, or pain in a leg or arm
+ Trouble speaking or swallowing
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor if they bother you or do not go away:
Headache
Diarrhea
Stomach pain
Upset stomach
Nausea or vomiting
Dizziness
Fatigue
Weakness
Cough
Muscle or joint pain
Signs of a common cold
Muscle spasm
Nose or throat irritation
Mouth pain
Tooth pain
Change in skin color
* Pain in arms or legs
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of a urinary tract infection (UTI), including:
+ Blood in the urine
+ Burning or pain when passing urine
+ Frequent or urgent need to urinate
+ Fever
+ Lower stomach pain
+ Pelvic pain
Neurological symptoms, such as:
+ Weakness on one side of the body
+ Trouble speaking or thinking
+ Change in balance
+ Drooping on one side of the face
+ Blurred eyesight
Vision changes, including:
+ Change in eyesight
+ Eye pain
+ Severe eye irritation
Unusual bruising or bleeding while taking this medication or after stopping it
Confusion
Abdominal swelling
Swelling in the arms or legs
Fever or chills
Signs of a blood clot, such as:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, change of color, or pain in a leg or arm
+ Trouble speaking or swallowing
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor if they bother you or do not go away:
Headache
Diarrhea
Stomach pain
Upset stomach
Nausea or vomiting
Dizziness
Fatigue
Weakness
Cough
Muscle or joint pain
Signs of a common cold
Muscle spasm
Nose or throat irritation
Mouth pain
Tooth pain
Change in skin color
* Pain in arms or legs
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of liver problems: yellowing of skin or eyes (jaundice), dark urine, unusual tiredness, nausea, vomiting, pain in the upper right side of your stomach.
- Signs of blood clots: pain, swelling, warmth, or redness in an arm or leg; sudden shortness of breath; chest pain; sudden numbness or weakness on one side of your body; sudden vision changes.
- Unusual bleeding or bruising (though the medication is meant to help with this, report any new or worsening bleeding).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
A low platelet count caused by underlying health conditions.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
A low platelet count caused by underlying health conditions.
* If you are breastfeeding, as you should not breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Discuss any concerns or questions you have with your doctor.
Do not discontinue this medication without first consulting your doctor, as abruptly stopping it may increase your risk of developing severe thrombocytopenia (very low platelet count) and bleeding. If you need to stop taking this medication, talk to your doctor to determine the best course of action.
This medication may exacerbate existing cataracts or increase the risk of developing new cataracts. Consult your doctor about this potential risk and schedule an eye exam as recommended.
If you are of East or Southeast Asian descent, discuss your treatment options with your doctor, as you may require a lower initial dose of this medication.
Be aware that this medication has been associated with an increased risk of blood clots, which can be life-threatening and may lead to heart attack or stroke. Take precautions to prevent injuries and avoid falls or accidents. Consult your doctor to discuss this risk and ways to minimize it.
This medication is contraindicated in individuals with myelodysplastic syndrome (MDS), a certain bone marrow disorder. If you have MDS and take this medication, it may worsen your condition and increase the risk of transforming into acute myelogenous leukemia (AML), a type of blood cancer. If MDS progresses to AML, it may reduce your life expectancy. If you have MDS, consult your doctor before taking this medication.
Additionally, this medication may harm an unborn baby if taken during pregnancy. If you are pregnant or may become pregnant, it is crucial to use effective birth control while taking this medication and for a specified period after the last dose. Consult your doctor to determine the recommended duration of birth control use. If you become pregnant while taking this medication, notify your doctor immediately.
Do not discontinue this medication without first consulting your doctor, as abruptly stopping it may increase your risk of developing severe thrombocytopenia (very low platelet count) and bleeding. If you need to stop taking this medication, talk to your doctor to determine the best course of action.
This medication may exacerbate existing cataracts or increase the risk of developing new cataracts. Consult your doctor about this potential risk and schedule an eye exam as recommended.
If you are of East or Southeast Asian descent, discuss your treatment options with your doctor, as you may require a lower initial dose of this medication.
Be aware that this medication has been associated with an increased risk of blood clots, which can be life-threatening and may lead to heart attack or stroke. Take precautions to prevent injuries and avoid falls or accidents. Consult your doctor to discuss this risk and ways to minimize it.
This medication is contraindicated in individuals with myelodysplastic syndrome (MDS), a certain bone marrow disorder. If you have MDS and take this medication, it may worsen your condition and increase the risk of transforming into acute myelogenous leukemia (AML), a type of blood cancer. If MDS progresses to AML, it may reduce your life expectancy. If you have MDS, consult your doctor before taking this medication.
Additionally, this medication may harm an unborn baby if taken during pregnancy. If you are pregnant or may become pregnant, it is crucial to use effective birth control while taking this medication and for a specified period after the last dose. Consult your doctor to determine the recommended duration of birth control use. If you become pregnant while taking this medication, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Excessive platelet count (thrombocytosis)
- Increased risk of thrombotic events (blood clots)
- Liver enzyme elevations
What to Do:
There is no specific antidote. In case of overdose, monitor platelet counts closely and manage symptoms supportively. Consider oral administration of a polyvalent cation-containing product (e.g., calcium-containing antacid) to chelate eltrombopag and limit absorption. Contact a poison control center (e.g., 1-800-222-1222) or seek emergency medical attention immediately.
Drug Interactions
Major Interactions
- Polyvalent cation-containing products (e.g., antacids, dairy products, mineral supplements): Significantly reduce eltrombopag absorption. Administer eltrombopag at least 2 hours before or 4 hours after these products.
Moderate Interactions
- Statins (e.g., rosuvastatin, atorvastatin): Eltrombopag is an OATP1B1 and BCRP inhibitor, can increase statin concentrations. Consider dose reduction of statin and monitor.
- UGT substrates (e.g., irinotecan, raltegravir): Eltrombopag is a UGT1A1 and UGT1A3 inhibitor, may increase exposure to UGT substrates. Monitor for adverse effects.
- Other drugs that cause hepatotoxicity: Increased risk of liver injury.
Confidence Interactions
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, total bilirubin)
Rationale: To establish baseline liver function and identify pre-existing hepatic impairment, given the risk of hepatotoxicity.
Timing: Prior to initiation of therapy.
Complete Blood Count (CBC) with differential and platelet count
Rationale: To establish baseline platelet count and other hematologic parameters.
Timing: Prior to initiation of therapy.
Iron studies (serum ferritin, transferrin saturation)
Rationale: To assess iron status, as eltrombopag is an iron chelator.
Timing: Prior to initiation of therapy.
Ophthalmologic examination (slit lamp)
Rationale: To establish baseline for potential cataract development.
Timing: Prior to initiation of therapy.
Routine Monitoring
Liver Function Tests (ALT, AST, total bilirubin)
Frequency: Every 2 weeks for the first 2 months of therapy, then monthly thereafter.
Target: Within normal limits or stable from baseline.
Action Threshold: Discontinue if ALT/AST increase to âĨ3x ULN and are progressive, or persistent for âĨ4 weeks, or accompanied by increased direct bilirubin, or clinical symptoms of liver injury. Consider discontinuation if ALT/AST increase to âĨ5x ULN.
Complete Blood Count (CBC) with platelet count
Frequency: Weekly until a stable platelet count (âĨ50,000/mcL for ITP) is achieved, then monthly.
Target: Platelet count âĨ50,000/mcL (for ITP) or as clinically indicated for other conditions.
Action Threshold: Adjust dose to maintain platelet count. Discontinue if platelet count exceeds 400,000/mcL for 4 consecutive weeks (ITP/HCV) or 200,000/mcL (SAA) or if thrombosis occurs.
Signs and symptoms of thrombosis/thromboembolism
Frequency: Regularly throughout therapy.
Target: Absence of symptoms.
Action Threshold: Prompt evaluation and management if symptoms occur.
Signs and symptoms of liver injury
Frequency: Regularly throughout therapy.
Target: Absence of symptoms (e.g., jaundice, dark urine, fatigue, right upper quadrant pain).
Action Threshold: Prompt evaluation and management if symptoms occur.
Ophthalmologic examination (slit lamp)
Frequency: Annually.
Target: No new or worsening cataracts.
Action Threshold: Refer to ophthalmologist if changes noted.
Symptom Monitoring
- Signs of liver injury (e.g., unexplained nausea, vomiting, abdominal pain, fatigue, dark urine, jaundice, itching)
- Signs of thrombosis/thromboembolism (e.g., pain, swelling, tenderness in a leg, sudden shortness of breath, chest pain, sudden numbness or weakness on one side of the body, sudden vision changes)
- Signs of bleeding (e.g., easy bruising, petechiae, purpura, nosebleeds, gum bleeding, blood in urine or stool)
- Headache
- Muscle pain
- Nausea
- Diarrhea
Special Patient Groups
Pregnancy
Eltrombopag may cause fetal harm when administered to a pregnant woman. Based on animal studies, it can cause adverse developmental effects. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity based on animal data.
Second Trimester:
Potential for developmental toxicity based on animal data.
Third Trimester:
Potential for developmental toxicity based on animal data.
Lactation
It is not known whether eltrombopag is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with eltrombopag and for at least 21 days after the last dose.
Infant Risk:
Risk of serious adverse reactions (e.g., hepatotoxicity, effects on hematopoiesis) in the infant. Manufacturer advises against breastfeeding.
Pediatric Use
Approved for chronic ITP in patients 1 year and older, and for SAA in patients 2 years and older. Dosing adjustments are required for pediatric patients, especially those of East Asian ancestry. Close monitoring of LFTs and platelet counts is essential.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly and younger patients. However, due to the higher incidence of co-morbidities and concomitant medications in the elderly, dose selection should be cautious, and monitoring for adverse effects should be diligent.
Clinical Information
Clinical Pearls
- Strict adherence to administration instructions regarding food and polyvalent cations is crucial for optimal absorption and efficacy.
- Regular and diligent monitoring of liver function tests (LFTs) is paramount due to the risk of hepatotoxicity, especially during the initial phase of treatment.
- Patients should be educated on the signs and symptoms of liver injury and thrombosis and instructed to seek immediate medical attention if they occur.
- Risk of rebound thrombocytopenia (platelet count dropping below baseline) upon discontinuation of eltrombopag, requiring close monitoring.
- Eltrombopag is an iron chelator; monitor iron studies, especially in patients with pre-existing iron overload.
Alternative Therapies
- Romiplostim (another TPO receptor agonist)
- Avatrombopag (another TPO receptor agonist)
- Lusutrombopag (another TPO receptor agonist)
- Corticosteroids (e.g., prednisone for ITP)
- Intravenous Immunoglobulin (IVIG for ITP)
- Anti-D immunoglobulin (for Rh-positive ITP patients)
- Splenectomy (for refractory ITP)
- Immunosuppressants (e.g., cyclosporine, ATG for SAA)
Cost & Coverage
Average Cost:
Highly variable, typically several thousand USD per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization and may have high co-pays)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, we encourage you to discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.