Version May 2024
In patients with chronic hepatitis C, eltrombopag in combination with interferon and ribavirin may increase the risk of hepatic decompensation.
Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended.
Note: Do not use eltrombopag to normalize platelet counts.
Chronic hepatitis C-associated thrombocytopenia: Note: Use the lowest dose to achieve the target platelet count necessary to initiate antiviral therapy (peginterferon and ribavirin) or to avoid dose reductions of peginterferon during antiviral therapy. Discontinue eltrombopag when antiviral therapy is stopped.
Initial: Oral: 25 mg once daily; dose should be titrated based on platelet response. Maximum dose: 100 mg/day.
Dosage adjustment based on platelet response:
Platelet count <50,000/mm3 (after at least 2 weeks): Increase daily dose by 25 mg every 2 weeks; maximum dose: 100 mg/day.
Platelet count ≥200,000/mm3 and ≤400,000/mm3 (at any time): Reduce daily dose by 25 mg; reassess in 2 weeks.
Platelet count >400,000/mm3: Withhold dose; assess platelet count twice weekly; when platelet count <150,000/mm3, resume with the daily dose reduced by 25 mg (if taking 25 mg once daily, resume with 12.5 mg once daily).
Platelet count >400,000/mm3 after 2 weeks at the lowest dose: Discontinue treatment.
Immune thrombocytopenia (persistent or chronic): Note: Use the lowest dose to achieve and maintain platelet count ≥50,000/mm3 as needed to reduce the risk of bleeding. Discontinue eltrombopag if platelet count does not respond to a level that avoids clinically important bleeding after 4 weeks at the maximum of 75 mg/day.
Initial: Oral: 50 mg once daily (25 mg once daily for patients of East/Southeast Asian ancestry); dose should be titrated based on platelet response. Maximum dose: 75 mg/day.
Dosage adjustment based on platelet response:
Platelet count <50,000/mm3 (≥2 weeks after treatment initiation or a dose increase): Increase daily dose by 25 mg (if taking 12.5 mg once daily, increase dose to 25 mg once daily prior to increasing the dose amount by 25 mg daily); maximum: 75 mg/day.
Platelet count ≥200,000/mm3 and ≤400,000/mm3 (at any time): Reduce daily dose by 25 mg (if taking 25 mg once daily, decrease dose to 12.5 mg once daily); reassess in 2 weeks.
Platelet count >400,000/mm3: Withhold dose; assess platelet count twice weekly; when platelet count <150,000/mm3, resume with the daily dose reduced by 25 mg (if taking 25 mg once daily, resume with 12.5 mg once daily).
Platelet count >400,000/mm3 after 2 weeks at the lowest dose: Discontinue treatment.
Severe aplastic anemia, first-line treatment: Note: Initiate eltrombopag concurrently with standard immunosuppressive therapy (antithymocyte globulin [equine] and cyclosporine) (Ref). If baseline ALT or AST levels are >6 times ULN, do not initiate eltrombopag until transaminases are <5 times ULN.
Initial: Oral: 150 mg once daily for 6 months (decrease dose by 50% [to 75 mg once daily] for patients of East/Southeast Asian ancestry [eg, Chinese, Japanese, Korean, Taiwanese, Thai]); dose should be titrated based on platelet response (Ref).
Dosage adjustment based on platelet response:
Platelet count >200,000/mm3 to ≤400,000/mm3: Decrease the daily dose by 25 mg every 2 weeks to the lowest dose that maintains platelet count at ≥50,000/mm3.
Platelet count >400,000/mm3: Discontinue eltrombopag for 1 week; once platelets are <200,000/mm3, reinitiate eltrombopag with the dose reduced by 25 mg.
Severe aplastic anemia, refractory: Note: Use the lowest dose to achieve and maintain hematologic response. Hematologic response may take up to 16 weeks and requires dose titration. Discontinue therapy if hematologic response is not achieved after 16 weeks of treatment, for excessive platelet responses or for liver function abnormalities. Consider discontinuing if new cytogenetic abnormalities are observed.
Initial: Oral: 50 mg once daily (25 mg once daily for patients of East/Southeast Asian ancestry); dose should be titrated based on platelet response. Maximum dose: 150 mg/day.
Dosage adjustment based on platelet response:
Platelet count <50,000/mm3 (≥2 weeks after treatment initiation or a dose increase): Increase daily dose by 50 mg (if taking 25 mg once daily, increase dose to 50 mg once daily prior to increasing the dose amount by 50 mg daily); maximum: 150 mg/day.
Platelet count ≥200,000/mm3 and ≤400,000/mm3 (at any time): Reduce daily dose by 50 mg; reassess in 2 weeks.
Platelet count >400,000/mm3: Withhold dose for 1 week; when platelet count <150,000/mm3, resume with the daily dose reduced by 50 mg.
Platelet count >400,000/mm3 after 2 weeks at the lowest dose: Discontinue treatment.
For patients who achieve tri-lineage response, including transfusion independence, lasting at least 8 weeks, may reduce the dose by 50%. If counts remain stable after 8 weeks at the reduced dose, discontinue and monitor blood counts. If platelets counts drop to <30,000/mm3, hemoglobin to <9 g/dL, or ANC to <500/mm3, may reinitiate at the prior effective dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment is necessary.
Adjustment for hepatic impairment prior to initiating treatment:
Chronic hepatitis C-associated thrombocytopenia:
Initial: No dosage adjustment is necessary.
Immune thrombocytopenia: Note: In patients with immune thrombocytopenia (ITP) and hepatic impairment, wait 3 weeks (instead of 2 weeks) after therapy initiation or subsequent dosage changes prior to increasing dose.
Mild, moderate, or severe impairment (Child-Pugh classes A, B, or C): Initial: 25 mg once daily.
Patients of East/Southeast Asian ancestry with hepatic impairment (Child-Pugh classes A, B, or C): Initial: Consider 12.5 mg once daily.
Severe aplastic anemia, first-line treatment: Note: If baseline ALT or AST levels are >6 times ULN, do not initiate eltrombopag until transaminases are <5 times ULN.
Mild, moderate, or severe impairment (Child-Pugh classes A, B, or C): Initial: 75 mg once daily.
Severe aplastic anemia, refractory:
Mild, moderate, or severe impairment (Child-Pugh classes A, B, or C): Initial: 25 mg once daily.
Adjustment for hepatotoxicity during treatment:
Chronic hepatitis C-associated thrombocytopenia, ITP, severe refractory aplastic anemia: ALT levels ≥3 times the ULN in patients with normal hepatic function or ≥3 times baseline (or >5 times ULN, whichever is lower) in those with preexisting transaminase elevations and which are progressive, persistent (≥4 weeks), accompanied by increased direct bilirubin, or accompanied by clinical signs of liver injury or evidence of hepatic decompensation: Discontinue treatment. Hepatotoxicity may recur with re-treatment after therapy interruption, but if determined to be clinically beneficial, may cautiously resume treatment; monitor ALT weekly during dosage titration; permanently discontinue if liver function test elevations persist, worsen, or recur.
Severe aplastic anemia, first-line treatment:
ALT or AST >6 times ULN: Discontinue eltrombopag; once ALT or AST is <5 times ULN, reinitiate eltrombopag at the same dose.
ALT or AST >6 times ULN (after eltrombopag reinitiation): Discontinue eltrombopag and monitor ALT/AST at least every 3 to 4 days. Once ALT or AST is <5 times ULN, reinitiate eltrombopag at a daily dose reduced by 25 mg (compared to the previous dose). If ALT or AST returns to >6 times ULN on the reduced dose, reduce the daily eltrombopag dose by 25 mg until ALT or AST is <5 times ULN.
Severe aplastic anemia, first-line treatment: Thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction): Discontinue eltrombopag, but remain on antithymocyte globulin (equine) and cyclosporine.
Refer to adult dosing.
(For additional information see "Eltrombopag: Pediatric drug information")
Note: Do not use eltrombopag to normalize platelet counts. Due to possible bioavailability differences with product formulations, platelet counts should be monitored more closely when switching between oral suspension and tablets.
Aplastic anemia, severe (initial therapy): Note: If baseline ALT or AST levels are >6 times ULN, do not initiate eltrombopag until transaminases are <5 times ULN and adjust dose appropriately. Use as first-line therapy in combination with standard immunosuppressive treatment (antithymocyte globulin [equine] and cyclosporine) (Ref). Continue treatment for 6 months and adjust dose as needed based on platelet response or thrombosis.
Initial:
2 to 5 years: Initial: Oral: 2.5 mg/kg/dose once daily; maximum dose: 75 mg/dose; for patients of East/Southeast Asian ancestry (eg, Chinese, Japanese, Korean, Taiwanese, Thai), reduce initial dose to 1.25 mg/kg/dose once daily, maximum dose: 37.5 mg/dose.
6 to 11 years: Initial: Oral: 75 mg once daily; for patients of East/Southeast Asian ancestry (eg, Chinese, Japanese, Korean, Taiwanese, Thai), reduce initial dose to 37.5 mg once daily.
≥12 years: Initial: Oral: 150 mg once daily; for patients of East/Southeast Asian ancestry (eg, Chinese, Japanese, Korean, Taiwanese, Thai), reduce initial dose to 75 mg once daily.
Dosage adjustment based on platelet response or thrombosis:
Platelet count >200,000/mm3 to ≤400,000/mm3: Decrease dose by the following increments and intervals to the lowest dose that maintains platelet count at ≥50,000/mm3.
Children 2 to <12 years: Decrease the daily dose by 12.5 mg every 2 weeks.
Children ≥12 years and Adolescents: Decrease the daily dose by 25 mg every 2 weeks.
Platelet count >400,000/mm3: Discontinue eltrombopag for 1 week; once platelets are <200,000/mm3, reinitiate eltrombopag at the following reduced dose:
Children 2 to <12 years: Decrease the daily dose by 12.5 mg.
Children ≥12 years and Adolescents: Decrease the daily dose by 25 mg.
Thrombosis (eg, DVT, PE, stroke, myocardial infarction): Discontinue eltrombopag.
Chronic immune (idiopathic) thrombocytopenia (ITP): Note: Use the lowest dose to achieve and maintain platelet count ≥50,000/mm3 as needed to reduce the risk of bleeding. Discontinue if platelet count does not respond to a level that avoids clinically important bleeding after 4 weeks at the maximum daily dose of 75 mg.
Initial:
Children 1 to <6 years: Initial: Oral: 25 mg once daily (no dosage adjustment required for patients of East/Southeast Asian ancestry).
Children ≥6 years and Adolescents: Initial: Oral: 50 mg once daily; for patients of East/Southeast Asian ancestry (eg, Chinese, Japanese, Korean, Taiwanese), reduce initial dose to 25 mg once daily.
Dosage adjustment based on platelet response: Adjust dose to achieve/maintain platelet count ≥50,000/mm3 as necessary to reduce bleeding risk; maximum daily dose: 75 mg/day. Monitor platelet count weekly until stabilizes and then monthly; additional monitoring may be necessary based on response or any changes in product formulation (oral suspension/tablets).
If platelet count <50,000/mm3 (≥2 weeks after treatment initiation or a dose increase): Increase daily dose by 25 mg (if taking 12.5 mg once daily, increase dose to 25 mg once daily prior to increasing the dose amount by 25 mg/day; maximum daily dose: 75 mg/day once daily.
If platelet count ≥200,000/mm3 and ≤400,000/mm3 (at any time): Reduce daily dose by 25 mg (if previous dose 25 mg once daily, decrease dose to 12.5 mg once daily); reassess platelet count in 2 weeks.
If platelet count >400,000/mm3: Withhold doses; assess platelet count twice weekly; when platelet count <150,000/mm3, resume with the daily dose reduced by 25 mg (if previous dose 25 mg once daily, resume with 12.5 mg once daily).
If platelet count >400,000/mm3 after 2 weeks at the lowest dose: Discontinue treatment.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment is necessary.
Baseline hepatic impairment (prior to therapy initiation):
Aplastic anemia, severe (first-line):
ALT or AST >6 times ULN: Do not initiate eltrombopag therapy until transaminases are <5 times ULN.
Mild, moderate, or severe hepatic impairment: Use reduced initial doses.
Children 2 to 5 years: Oral: 1.25 mg/kg/dose once daily; maximum dose: 37.5 mg/dose.
Children 6 to 11 years: Oral: 37.5 mg once daily.
Children ≥12 years and Adolescents: Oral: 75 mg once daily.
Chronic immune (idiopathic) thrombocytopenia (ITP): Note: In patients with ITP and hepatic impairment, wait 3 weeks (instead of 2 weeks) after therapy initiation or subsequent dosage changes prior to increasing dose.
Children 1 to <6 years: There are no dosage adjustments provided by the manufacturer; use with caution.
Children ≥6 years and Adolescents:
Mild, moderate, or severe impairment: Initial: Oral: 25 mg once daily.
Patients of East/Southeast Asian ancestry with hepatic impairment (mild, moderate, or severe): Initial: Oral: 12.5 mg once daily.
Hepatic impairment during treatment:
Aplastic anemia, severe (first-line ):
ALT or AST >6 times ULN: Children ≥2 years and Adolescents: Discontinue eltrombopag; once ALT or AST is <5 times ULN, reinitiate eltrombopag at the same dose.
ALT or AST >6 times ULN (after eltrombopag reinitiation): Discontinue eltrombopag and monitor ALT/AST at least every 3 to 4 days. Once ALT or AST is <5 times ULN, reinitiate eltrombopag at a reduced daily dose.
Children 2 to 11 years: Reduce daily dose by at least 15% to nearest dose able to be administered.
Children ≥12 years and Adolescents: Reduce by 25 mg (compared to the previous dose).
If ALT or AST returns to >6 times ULN on the reduced dose:
Children 2 to 11 years: Further reduce daily dose by at least 15% to nearest dose able to be administered until ALT or AST is <5 times ULN.
Children ≥12 years and Adolescents: Further reduce dose by 25 mg until ALT or AST is <5 times ULN.
Chronic ITP: Children ≥1 year and Adolescents: ALT levels ≥3 times ULN in patients with normal hepatic function or ≥3 times baseline (>5 times ULN, whichever is lower) in those with preexisting transaminase elevations and which are progressive, persistent (≥4 weeks), accompanied by increased direct bilirubin, or accompanied by clinical signs of liver injury or evidence of hepatic decompensation: Discontinue treatment. Hepatotoxicity may recur with retreatment after therapy interruption, but if determined to be clinically beneficial, may cautiously resume treatment; monitor ALT weekly during dosage titration; permanently discontinue if liver function test elevations persist, worsen, or recur.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Hepatic: Abnormal hepatic function tests (adults: 11%)
Respiratory: Upper respiratory tract infection (children and adolescents: 17%; adults: 7%), nasopharyngitis (children and adolescents: 12%)
1% to 10%:
Cardiovascular: Thromboembolic disease (adults: 6%), thrombosis (adults: 3%), portal vein thrombosis (adults: 2%)
Dermatologic: Skin rash (3% to 5%), alopecia (adults: 2%)
Gastrointestinal: Diarrhea (9%), nausea (adults: 9%), abdominal pain (children and adolescents: 8%), toothache (children and adolescents: 6%), vomiting (adults: 6%), xerostomia (adults: 2%)
Genitourinary: Urinary tract infection (adults: 5%)
Hepatic: Increased serum alanine aminotransferase (5% to 6%), increased serum aspartate aminotransferase (4%), increased serum alkaline phosphatase (adults: 2%), hepatotoxicity (≤1%)
Infection: Influenza (adults: 3%)
Neuromuscular & skeletal: Myalgia (adults: 5%), back pain (adults: 3%), paresthesia (adults: 3%), musculoskeletal pain (adults: 2%)
Ophthalmic: Cataract (children and adolescents: 1%)
Respiratory: Cough (children and adolescents: 9%), oropharyngeal pain (4% to 8%), pharyngitis (adults: 4%), rhinorrhea (children and adolescents: 4%)
Miscellaneous: Fever (children and adolescents: 9%)
Frequency not defined: Hematologic & oncologic: Hemorrhage
<1%, postmarketing, and/or case reports: Skin discoloration (including hyperpigmentation and skin yellowing), thrombotic microangiopathy (with acute renal failure)
There are no contraindications listed in the manufacturer’s US labeling.
Canadian labeling: Hypersensitivity to eltrombopag or any component of the formulation; severe hepatic impairment (Child-Pugh class C)
Concerns related to adverse effects:
• Cataract formation: Cataract formation or worsening has been observed with eltrombopag; most patients had preexisting risk factors for cataracts, including corticosteroid use.
• Hepatotoxicity: Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. Liver enzyme elevations may occur; drug-induced liver injury has been reported. Eltrombopag inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinemia; obtain fractionation for elevated bilirubin levels. Hepatotoxicity may recur with re-treatment after therapy interruption.
• Thromboembolism: Thrombotic/thromboembolic complications may occur with increases in platelet levels with eltrombopag. Complications including venous or arterial events were observed at low and normal platelet counts. Consider the potential for an increased risk of thromboembolism with eltrombopag in patients with known risk factors for thromboembolism (eg, factor V Leiden, ATIII deficiency, antiphospholipid syndrome, chronic liver disease). To minimize the risk for thrombotic complications, do not use eltrombopag in an attempt to normalize platelet counts; follow dosage adjustment recommendations to achieve/maintain target platelet counts. Thrombotic events, primarily involving the portal venous system, were more commonly seen in eltrombopag-treated patients with chronic hepatitis C with thrombocytopenia (when compared to placebo). Thrombotic events (including portal venous thrombosis) were also reported in a study of non-immune thrombocytopenia (ITP) thrombocytopenic patients with chronic liver disease undergoing elective invasive procedures receiving eltrombopag 75 mg once daily. Symptoms of portal vein thrombosis include abdominal pain, nausea, vomiting, and diarrhea. The risk for portal venous thrombosis is increased in thrombocytopenic patients with chronic liver disease receiving 75 mg once daily for 2 weeks as preparation for invasive procedures.
Disease-related concerns:
• Chronic hepatitis C infection: May increase risk of hepatic decompensation when used in combination with interferon and ribavirin in patients with chronic hepatitis C. In clinical trials, patients with low albumin (<3.5 g/dL) or a Model for End-Stage Liver Disease (MELD) score ≥10 at baseline had an increased risk of hepatic decompensation; closely monitor these patients during therapy. Indirect hyperbilirubinemia is commonly observed with eltrombopag when used in combination with peginterferon and ribavirin. In addition, ascites, encephalopathy, and thrombotic events were reported more frequently than placebo in chronic hepatitis C trials.
• Myelodysplastic syndromes: Eltrombopag is not indicated for the treatment of myelodysplastic syndromes (MDS). A clinical trial comparing the combination of azacitidine plus eltrombopag to azacitidine plus placebo in patients with intermediate-1, intermediate-2, or high-risk MDS with thrombocytopenia was terminated due to lack of efficacy and for safety concerns (including increased progression to acute myeloid leukemia [AML]). Increased relative risks of death and progression to AML in the eltrombopag arm compared to placebo were observed in the study.
Alvaiz: FDA approved November 2023; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Alvaiz is indicated for the treatment of thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy; thrombocytopenia in adult patients with chronic hepatitis C; and adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. Alvaiz tablets are formulated as eltrombopag choline compared to the currently available product, Promacta, which is formulated as eltrombopag olamine. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Promacta: 12.5 mg (1 ea, 30 ea); 25 mg (1 ea, 30 ea)
Tablet, Oral:
Promacta: 12.5 mg
Promacta: 25 mg [contains fd&c yellow #6(sunset yellow)alumin lake]
Promacta: 50 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Promacta: 75 mg
No
Pack (Promacta Oral)
12.5 mg (per each): $289.87
25 mg (per each): $289.88
Tablets (Promacta Oral)
12.5 mg (per each): $289.87
25 mg (per each): $289.87
50 mg (per each): $524.56
75 mg (per each): $786.85
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Revolade: 25 mg, 50 mg
Generic: 25 mg, 50 mg
Oral: Administer on an empty stomach or with a low-calcium (≤50 mg) meal. Swallow tablets whole; do not split, chew, or crush and mix with food or liquids. Prepare the suspension with cool or cold water only (do not use hot water); discard any suspension not administered within 30 minutes after reconstitution. Do not reuse oral dosing syringes; use a new single-use syringe to prepare and administer each dose. If powder or suspension spills during preparation or administration, consider wearing disposable gloves during spill clean-up to avoid staining skin. Administer eltrombopag at least 2 hours before or 4 hours after antacids, foods high in calcium (eg, dairy products, calcium-fortified juices, certain fruits, certain vegetables), or supplements containing polyvalent cations (eg, iron, calcium, aluminum, magnesium, selenium, zinc). Do not administer more than one dose within 24 hours.
Administer on an empty stomach or with a low-calcium (≤50 mg) meal. Administer at least 2 hours before or 4 hours after antacids, foods high in calcium (eg, dairy products, calcium-fortified juices), or supplements containing polyvalent cations (eg, iron, calcium, aluminum, magnesium, selenium, zinc). Do not administer more than 1 dose within 24 hours.
Tablets: Swallow tablets whole; do not split, chew, or crush and mix with food or liquids.
Oral suspension: Administer dose immediately after preparation; if dose not administered within 30 minutes of preparation, discard unused suspension in trash (do not pour down drain) and mix a new dose. Place tip of oral dosing syringe into child's mouth against the inside of child's cheek and slowly depress plunger to administer dose. Do not reuse oral dosing syringes; a new single-use oral syringe must be used to prepare and administer each dose. After administration, place any waste in the trash (not sink drain); clean mixing bottle and cap by rinsing under running water and allow to air-dry (bottle may stain, this is normal); wash hands with soap and water. If powder or suspension spills during administration, consider wearing disposable gloves during spill clean-up to avoid staining skin.
An FDA-approved patient medication guide, which is available with the product and as follows, must be dispensed with this medication:
Alvaiz: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216774s000lbl.pdf#page=30
Aplastic anemia, severe: First-line treatment (in combination with standard immunosuppressive therapy) of severe aplastic anemia in patients ≥2 years of age; treatment of severe (refractory) aplastic anemia in patients who have had an insufficient response to immunosuppressive therapy
Chronic hepatitis C infection-associated thrombocytopenia: Treatment of thrombocytopenia in patients with chronic hepatitis C (CHC) to allow the initiation and maintenance of interferon-based therapy.
Immune thrombocytopenia (persistent or chronic): Treatment of thrombocytopenia in adult and pediatric patients ≥1 year of age with persistent or chronic immune thrombocytopenia (ITP) who have had insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Limitations of use: For ITP, eltrombopag should only be used if the degree of thrombocytopenia and clinical condition increase the risk for bleeding. For CHC, eltrombopag should only be used if the degree of thrombocytopenia prevents initiation of or limits the ability to maintain interferon-based therapy. Safety and efficacy have not been established when used in combination with direct-acting antiviral agents without interferon for treatment of CHC infection. Eltrombopag is not indicated for the treatment of myelodysplastic syndromes.
Eltrombopag may be confused with avatrombopag, lusutrombopag.
Substrate of BCRP/ABCG2, CYP1A2 (minor), CYP2C8 (minor), UGT1A1, UGT1A3; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, OATP1B1/1B3 (SLCO1B1/1B3), UGT1A3, UGT1A6, UGT2B15, UGT2B7
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider therapy modification
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Eltrombopag may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. Risk D: Consider therapy modification
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider therapy modification
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
CycloSPORINE (Systemic): May decrease the serum concentration of Eltrombopag. Risk C: Monitor therapy
Deferiprone: UGT1A6 Inhibitors may increase the serum concentration of Deferiprone. Risk X: Avoid combination
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: Avoid combination
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Risk D: Consider therapy modification
LORazepam: UGT2B15 Inhibitors may increase the serum concentration of LORazepam. Management: Avoid coadministration of UGT2B15 inhibitors and extended release lorazepam capsules. If coadministration is required, discontinue lorazepam extended release capsules and use lorazepam tablets instead. Monitor for increased lorazepam toxicities. Risk D: Consider therapy modification
Mitapivat: May decrease the serum concentration of UGT1A1 Substrates. Risk C: Monitor therapy
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors): Eltrombopag may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Polyvalent Cation Containing Products: May decrease the serum concentration of Eltrombopag. Management: Administer eltrombopag at least 2 hours before or 4 hours after oral administration of any polyvalent cation containing product. Risk D: Consider therapy modification
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: Avoid combination
Rosuvastatin: Eltrombopag may increase the serum concentration of Rosuvastatin. Management: Consideration a preventive 50% reduction in rosuvastatin adult dose when starting this combination. Risk D: Consider therapy modification
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
Calcium-rich (>50 mg) foods decrease the absorption of eltrombopag. Management: Administer on an empty stomach or with a low-calcium (≤50 mg) meal. Administer eltrombopag at least 2 hours before and 4 hours after foods high in calcium.
Patients who could become pregnant should use effective contraception (methods that result in <1% pregnancy rates) during eltrombopag therapy and for at least 7 days after the last eltrombopag dose.
If used in combination with ribavirin, all warnings related to the use of ribavirin contraception should be followed. Refer to the ribavirin monograph for additional information.
Outcome data following maternal use of eltrombopag for the treatment of thrombocytopenia in pregnancy are limited primarily to case reports (Favier 2018; Mendicino 2021; Michel 2020; Purushothaman 2016; Sammartano 2020; Shibata 2022; Suzuki 2018; Weingarten 2020).
Thrombopoietin (TPO) receptor agonists are not currently a preferred treatment of immune thrombocytopenia during pregnancy; use may be considered in very serious cases when other therapies have failed. If a TPO receptor agonist is needed, an agent other than eltrombopag is preferred (Provan 2019).
If used in combination with ribavirin, all warnings related to the use of ribavirin and pregnancy should be followed. Refer to the ribavirin monograph for additional information.
It is not known if eltrombopag is present in breast milk.
Due to the potential for serious adverse effects in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Calcium-rich (>50 mg) foods decrease the absorption of eltrombopag.
Chronic hepatitis C-associated thrombocytopenia: CBC with differential and platelet count (weekly at initiation and during dosage titration(s), then monthly when stable; after cessation, monitor weekly for ≥4 weeks; when switching between the oral suspension and tablet, monitor platelet counts weekly for 2 weeks, then monthly when stable). LFTs, including ALT, AST, and bilirubin (baseline, every 2 weeks during dosage titration(s), then monthly after a stable dose is achieved; repeat abnormal LFTs within 3 to 5 days; if confirmed abnormal, monitor weekly until abnormalities resolve, stabilize, or return to baseline). Obtain bilirubin fractionation (for elevated bilirubin). If re-treating after therapy interruption for hepatotoxicity (if potential treatment benefits outweigh risks), monitor LFTs weekly during dosage adjustment phase.
Immune thrombocytopenia: CBC with differential and platelet count (weekly at initiation and during dosage titration(s), then monthly when stable; after cessation, monitor weekly for ≥4 weeks; when switching between the oral suspension and tablet, monitor platelet counts weekly for 2 weeks, then monthly when stable). LFTs, including ALT, AST, and bilirubin (baseline, every 2 weeks during dosage titration(s), then monthly after a stable dose is achieved; repeat abnormal LFTs within 3 to 5 days; if confirmed abnormal, monitor weekly until abnormalities resolve, stabilize, or return to baseline). Obtain bilirubin fractionation (for elevated bilirubin). If re-treating after therapy interruption for hepatotoxicity (if potential treatment benefits outweigh risks), monitor LFTs weekly during dosage adjustment phase.
Severe aplastic anemia, first-line treatment: CBC with differential and platelets (regularly throughout therapy). ALT, AST, and bilirubin prior to eltrombopag initiation, every other day while hospitalized for antithymocyte globulin (equine) therapy, and then every 2 weeks during treatment.
Severe aplastic anemia, refractory: CBC with differential and platelets (regularly throughout therapy). LFTs, including ALT, AST, and bilirubin (baseline, every 2 weeks during dosage titration(s), then monthly after a stable dose is achieved; repeat abnormal LFTs within 3 to 5 days; if confirmed abnormal, monitor weekly until abnormalities resolve, stabilize, or return to baseline). Obtain bilirubin fractionation (for elevated bilirubin). If re-treating after therapy interruption for hepatotoxicity (if potential treatment benefits outweigh risks), monitor LFTs weekly during dosage adjustment phase.
All indications: Monitor regularly for signs and symptoms of cataracts; obtain ophthalmic exam at baseline and during therapy. Monitor for signs/symptoms of thromboembolism. Monitor adherence.
Target platelet count (with treatment) of 50,000 to 200,000/mm3; platelet life span: 8 to 11 days
Eltrombopag is a thrombopoietin (TPO) nonpeptide agonist which increases platelet counts by binding to and activating the human TPO receptor (also known as cMpl). Activates intracellular signal transduction pathways to increase proliferation and differentiation of megakaryocytes.
Onset of action: Platelet count increase: Within 1 to 2 weeks
Duration: Platelets return to baseline: 1 to 2 weeks after last dose
Protein binding: >99%
Metabolism: Extensive hepatic metabolism; via CYP1A2, 2C8 oxidation and UGT1A1, 1A3 glucuronidation
Bioavailability: At least 52%; in adults, plasma AUC was increased by 22% with the oral suspension versus tablets
Half-life elimination: ~21 to 32 hours in healthy individuals; ~26 to 35 hours in patients with ITP
Time to peak, plasma: 2 to 6 hours
Excretion: Feces (59%, ~20% as unchanged drug); urine (31%, as metabolites)
Altered kidney function: Following a single 50 mg dose, plasma AUC was 32% to 36% lower in patients with mild-to-moderate renal impairment (estimated CrCl 30 to 80 mL/minute) and 60% lower in patients with severe renal impairment (CrCl <30 mL/minute) compared with healthy patients.
Hepatic function impairment: Following a single 50 mg dose, plasma AUC was 41% higher in patients with mild hepatic impairment (Child-Pugh class A) and approximately two-fold higher in patients with moderate-to-severe hepatic impairment (Child-Pugh class B and class C, respectively) when compared to subjects with normal hepatic function. Following repeat doses of eltrombopag in patients with chronic liver disease with thrombocytopenia, the AUC increased 87% to 110% in patients with mild hepatic impairment, and 141% to 240% in patients with moderate hepatic impairment. The eltrombopag half-life was prolonged 3- and 4-fold in mild and moderate hepatic impairment, respectively, in patients with chronic liver disease with thrombocytopenia. The AUC increased with increasing Child-Pugh score in patients with chronic hepatitis C with thrombocytopenia; patients with mild impairment had ~100% to 144% higher plasma AUC, compared to healthy subjects.
Pediatric: Plasma eltrombopag apparent clearance following oral administration (CL/F) increased with increasing body weight. Pediatric patients of East/Southeast Asian ancestry with immune thrombocytopenia (ITP) had ~43% higher plasma eltrombopag AUC(0-τ) values compared with patients not of East/Southeast Asian ancestry.
Race/ethnicity: Eltrombopag exposure was 50% to 55% higher in patients of East/Southeast Asian ancestry with ITP or chronic hepatitis. Eltrombopag exposure in Black subjects was ~40% higher (than that in White subjects) in 1 study, although 3 other studies found similar exposure.
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