Eltrombopag
Eltrombopag is used to treat low blood platelet counts in adults with chronic immune (idiopathic) thrombocytopenia (ITP), when certain other medicines, or surgery to remove the spleen, have not worked well enough. ITP is a condition that may cause unusual bruising or bleeding due to an abnormally low number of platelets in the blood.
Mechanism of effect
Eltrombopag is an orally bioavailable, small-molecule TPO-receptor agonist that interacts with the transmembrane domain of the human TPO-receptor. Eltrombopag is a stimulator of STAT and JAK phosphorylation. Unlike recombinant TPO or romiplostim, Eltrombopag does not activate the AKT pathway in any way. It should be noted that when given to patients with aplastic anemia, other lineages besides platelet count were increased, suggesting that either eltrombopag enhanced the effect of TPO in vivo; or there is a yet uncovered mechanism of action at work.
Pharmacodynamic
Not Available
Pharmacokinetics
Bioavailability: >52% (single 75-mg dose)
Peak Plasma Time: 2-6 hr
Effect of food
- A standard high-fat breakfast (876 calories, 52 g fat, 71 g carbohydrate, 34 g protein, and 427 mg calcium) significantly decreased plasma eltrombopag AUC by ~59% and peak plasma concentration by 65% and delayed peak plasma concentrationby 1 hr
- Calcium content of this meal may have also contributed to this decrease in exposure
Protein bound: >99%
Concentration of eltrombopag in blood cells: ~ 50-79%
Metabolism
Extensively metabolized predominantly through pathways including cleavage, oxidation, and conjugation with glucuronic acid, glutathione, or cysteine
In vitro studies suggest that CYP1A2 and CYP2C8 are responsible for the oxidative metabolism
UGT1A1 and UGT1A3 are responsible for the glucuronidation
Half-life: 26-35 hr (in patients with ITP)
Excretion: Feces (59%); urine (31%)
Drug indications
prevent bleeding episodes in people with chronic immune thrombocytopenic purpura (ITP) prevent bleeding in adults with chronic hepatitis C who are treated with an interferon treat severe aplastic anemia in adults and children who are at least 2 years old.
Dosage
Adult
Chronic Immune Thrombocytopenia
Indicated in patients with insufficient response to corticosteroids, immunoglobulins, or splenectomy
Use only in patients with ITP whose clinical condition increases bleeding risk
Initial: 50 mg PO qDay
Maintenance: Adjust dose to achieve and maintain platelet count (Plt) >50 x 10^9/L to reduce risk of bleeding; not to exceed 75 mg/day
Chronic Hepatitis C-associated Thrombocytopenia
Initial: 25 mg PO qDay
Adjust dose in 25 mg increments q2weeks PRN to achieve target platelet count required to initiate/maintain antiviral therapy with pegylated interferon and ribavirin; not to exceed 100 mg/day
Severe Aplastic Anemia(SAA)
First-line therapy
- Initial dose: 150 mg PO qDay for 6 months
- Do not exceed initial dose; total duration is 6 months
Refractory SAA
- Initial dose: 50 mg PO qDay
- Adjust dose in 50-mg increments q2Weeks PRN to achieve target Plt ≥50 x 10^9/L as necessary; not exceed 150 mg/day; may take up to 16 weeks for hematologic response
Pediatric
Chronic Immune Thrombocytopenia
<1 year: Safety and efficacy not established
1-5 Years: Initiate at 25 mg qDay
≥6 years: Initiate at 50 mg PO qDay
Maintenance: Adjust dose to achieve and maintain platelet count (Plt) >50 x 10^9/L to reduce risk of bleeding; not to exceed 75 mg/day
Severe Aplastic Anemia
First-line therapy
- <2 years: Safety and efficacy not established
- 2-5 years: 2.5 mg/kg qDay for 6 months
- 6-11 years: 75 mg PO qDay for 6 months
- ≥12 years: 150 mg PO qDay for 6 months
Drug contraindications
None
Side effects
flu , Insomnia , Diarrhea , Headache , nausea , vomiting , vertigo , Urinary tract infection , Peripheral edema , fever , myalgia , Flu-like symptoms , Arthralgia , Increased ALT , Increased AST , Hyperbilirubinemia , itching , weakness , tiredness , Abdominal pain , Rash , RhinorrheaAbdominal pain, Alopecia , Anemia , Arthralgia , Asthenia , Back pain , Cataract , Chills , Cough , Decreased appetite , Diarrhea , Dizziness , Fatigue , Headache , Hyperbilirubinemia , Increased ALT , Increased AST , Increased blood bilirubin , Influenza , Influenza-like illness , Insomnia , Muscle spasms , Myalgia , Nasopharyngitis , Nausea , Oropharyngeal pain , Pain in extremity , Paresthesia , Peripheral edema , Pharyngitis , Pruritus , Pyrexia , Rash , Rhinorrhea , Skin discoloration including hyperpigmentation , Toothache , Transaminases increased , Upper respiratory tract infection , Urinary tract infection , Vomiting
Interactions
Sucralfate , Rosuvastatin , Zileuton , Calcium citrate , Magnesium hydroxide , Iron , Efavirenz , Iron polysaccharide , Sodium bicarbonate , Selenium , Iron sucrose , Simvastatin , Ferrous sulfate , Ferrous fumarate , carbonyl iron , Ferrous Gluconate , riociguat , magnesium citrate , pravastatin , fluvastatin , Calcium acetate , Calcium chloride , Eluxadoline , sodium citrate + citric acid , Fluvoxamine , Magnesium oxide , Magnesium sulfate , Calcium Gloconate , Calcium carbonate , Pitavastatin , Aluminium Mg , ELBASVIR/GRAZOPREVIR , magnesium chloride , Biolectra Magnesium , Iron Dextran Complex , Remdesivir , lasmiditan , talazoparib , ArtesunateAlerts
If patient with hepatic impairment (Child-Pugh Class A, B, C) initiates therapy for first- line treatment of severe aplastic anemia, reduce initial dose
In aplastic anemia, use lowest dose to achieve and maintain hematologic response; discontinue if no hematologic response observed after 16 weeks of therapy, excessive platelet count responses or liver test abnormalities
Chronic hepatitis C with cirrhosis may increase risk of hepatic decompensation and death when treated with alfa interferons; no dosage adjustment is recommended in patients with chronic hepatitis C and hepatic impairment
Not indicated for the treatment of patients with myelodysplastic syndromes (MDS); increased risk of death and progression of MDS to acute myeloid leukemia observed in a clinical trial showing an increased relative risk of progression to AML by 166%
Thrombotic/thromboembolic complications may result from increases in platelet counts with therapy
Portal vein thrombosis reported in patients with chronic liver disease receiving therapy
Consider potential risk of thromboembolism when administering to patients with known risk factors for thromboembolism (eg, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, chronic liver disease).
Risk of thrombocytopenia and hemorrhage after discontinuation
Not for normalizing platelet counts; for use only when degree of thrombocytopenia and clinical conditions increase risk for bleeding in patients with chronic immune idiopathic thrombocytopenia
May develop or worsen cataracts; screen before administering and during treatment
Discontinue if platelet count does not respond to a level to avoid clinically important bleeding after 4 weeks at maximum recommended dose
In hepatitis C, use only when thrombocytopenia prevents initiation and maintenance of interferon-based therapy; discontinue if antiviral therapy discontinued
Drug interactions overview
- Polyvalent cations
- Eltrombopag chelates polyvalent cations (eg, iron, calcium, aluminum, magnesium, selenium, zinc) in foods, mineral supplements, and antacids
- Administer at least 2 hr before or 4 hr after any medications or products containing polyvalent cations such as antacids, dairy products, and mineral supplements to avoid significant reduction in absorption
- OATP1B1 or BCRP transporters
- Use caution when coadministering with OATP1B1 substrates (eg, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or BCRP (eg, imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan)
- Monitor closely for signs/symptoms of excessive exposure to OATP1B1 or BCRP substrates and consider reducing the dose of these drugs, if appropriate
Black Box Warnings
Risk for hepatic decompensation in chronic hepatitis C patients
- Risk of hepatotoxicity
- In patients with chronic hepatitis C, eltrombopag in combination with interferon and ribavirin may increase risk of hepatic decompensation
- May increase risk of severe and potentially life-threatening hepatotoxicity
Points of recommendation
Take Eltrombopag exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.
Take Eltrombopag on an empty stomach, at least 1 hour before or 2 hours after a meal.
Do not take Eltrombopag with dairy products or calcium-fortified juice.
Mix the oral suspension powder only with water. Use a new dosing syringe each time you mix the medicine, to measure the water and to give the correct dose.
Swallow the tablet whole and do not crush, chew, or break it.
You will need frequent blood tests to check your liver function. Your eyes may also need to be checked for signs of cataract formation.
Eltrombopag doses are sometimes based on weight in children. Your child's dose needs may change if the child gains or loses weight.
It may take up to 4 weeks of taking this medicine before it is completely effective in preventing bleeding episodes. Keep taking the medication as directed and tell your doctor if you have any bruising or bleeding episodes after 4 weeks of treatment.
Store at room temperature away from moisture and heat. Keep the tablets in their original container, along with the packet or canister of moisture-absorbing preservative. After mixing Eltrombopag oral suspension, store the liquid at room temperature and use it within 30 minutes.
After you stop taking Eltrombopag, your risk of bleeding or bruising may be even higher than it was before you started treatment. Be extra careful to avoid cuts or injury for at least 4 weeks after you stop taking this medicine. Your blood will need to be tested weekly during this time.
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Pregnancy level
Not Assigned
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