Eltrombopag

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Packet, Oral:

Promacta: 12.5 mg (1 ea, 30 ea)

Tablet, Oral:

Promacta: 12.5 mg

Promacta: 25 mg [contains fd&c yellow #6 aluminum lake]

Promacta: 50 mg [contains fd&c blue #2 aluminum lake]

Promacta: 75 mg

Pharmacology

Mechanism of Action

Eltrombopag is a thrombopoietin (TPO) nonpeptide agonist which increases platelet counts by binding to and activating the human TPO receptor. Activates intracellular signal transduction pathways to increase proliferation and differentiation of marrow progenitor cells.

Pharmacokinetics/Pharmacodynamics

Metabolism

Extensive hepatic metabolism; via CYP1A2, 2C8 oxidation and UGT1A1, 1A3 glucuronidation

Excretion

Feces (59%, ~20% as unchanged drug); urine (31%, as metabolites)

Onset of Action

Platelet count increase: Within 1 to 2 weeks

Time to Peak

2 to 6 hours

Duration of Action

Platelets return to baseline: 1 to 2 weeks after last dose

Half-Life Elimination

~21 to 32 hours in healthy individuals; ~26 to 35 hours in patients with ITP

Protein Binding

>99%

Use in Specific Populations

Special Populations: Renal Function Impairment

Following a single 50 mg dose, plasma AUC was 32% to 36% lower in subjects with mild-to-moderate renal impairment (estimated CrCl 30 to 80 mL/minute) and 60% lower in subjects with severe renal impairment (CrCl <30 mL/minute) compared with healthy subjects.

Special Populations: 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 patients with normal hepatic function. Following repeat doses of eltrombopag in thrombocytopenic patients with chronic liver disease, the AUC increased 87% to 110% in patients with mild hepatic impairment, and 141% to 240% in patients with moderate hepatic impairment. Half-life was prolonged 3- and 4-fold in mild and moderate hepatic impairment in thrombocytopenic patients with chronic liver disease, respectively. AUC increased with increasing Child-Pugh score in chronic hepatitis C patients; patients with chronic hepatitis C and mild impairment had ~100% to 144% higher plasma AUC than healthy subjects.

Special Populations: Children

Plasma eltrombopag apparent clearance following oral administration (CL/F) increased with increasing body weight. Asian pediatric patients with ITP had ~43% higher plasma eltrombopag AUC(0-τ) values compared with non-Asian patients.

Special Populations: Race

Eltrombopag exposure is 50% to 55% higher in Asian (eg, Chinese, Japanese, Korean, or Taiwanese) subjects with ITP compared with non-Asian subjects. An ~40% higher systemic exposure in healthy African-American subjects was found in 1 study, although 3 other studies found similar exposure.

Use: Labeled Indications

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.

Chronic immune thrombocytopenia: Treatment of thrombocytopenia in adult and pediatric patients ≥1 year of age with 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 (MDS).

Contraindications

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)

Dosage and Administration

Dosing: Adult

Note: Do not use eltrombopag to normalize platelet counts.

Chronic immune thrombocytopenia (ITP): Oral: 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 of 75 mg/day.

Initial: 50 mg once daily (25 mg once daily for patients of Asian ethnicity [eg, Chinese, Japanese, Korean, Taiwanese]); 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

Chronic hepatitis C-associated thrombocytopenia: Oral: 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 when antiviral therapy is stopped.

Initial: 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

Severe aplastic anemia, first-line treatment: Oral: Note: Initiate eltrombopag concurrently with standard immunosuppressive therapy (antithymocyte globulin [equine] and cyclosporine; Townsley 2017). If baseline ALT or AST levels are >6 times ULN, do not initiate eltrombopag until transaminases are <5 times ULN.

Initial: 150 mg once daily for 6 months (75 mg once daily for patients of Asian ethnicity [eg, Chinese, Japanese, Korean, Taiwanese, Thai]); dose should be titrated based on platelet response.

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: Oral: 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: 50 mg once daily (25 mg once daily for patients of Asian ethnicity); 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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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) (Townsley 2017). 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 Asian ethnicity (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 Asian ethnicity (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 Asian ethnicity (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 Asian ancestry)

Children ≥6 years and Adolescents: Initial: Oral: 50 mg once daily; for patients of East Asian ethnicity (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.

Dosing: Adjustment for Toxicity

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.

Reconstitution

The oral suspension must be reconstituted with cool or cold water only (do not use hot water). Fill the provided single-use oral syringe with 20 mL of drinking water and empty into the mixing bottle; use a new single-use oral dosing syringe to prepare each dose. Add the appropriate eltrombopag dose to the mixing bottle; gently and slowly shake the bottle for at least 20 seconds to mix. If not used immediately, suspension may be stored for up to 30 minutes at room temperature; discard any solution if not used within 30 minutes. Following administration, discard the used oral dosing syringe and any suspension remaining in bottle in trash (do not dispose of in drain); clean supplies by rinsing the bottle and lid under running water and air-dry (bottle may stain, this is normal); wash hands with soap and water. If powder or suspension spills during preparation or administration, consider wearing disposable gloves during spill clean-up to avoid staining skin.

Administration

Oral: Administer on an empty stomach, 1 hour before or 2 hours after a 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 and calcium-fortified juices), or supplements containing polyvalent cations (eg, iron, calcium, aluminum, magnesium, selenium, zinc). Do not administer more than one dose within 24 hours.

Dietary Considerations

Food, especially dairy products, may decrease the absorption of eltrombopag.

Storage

Oral suspension: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Once reconstituted (if not used immediately), the suspension may be stored for a maximum of 30 minutes between 20°C and 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Discard the mixture if not used within 30 minutes.

Tablets: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Dispense in original bottle.

Drug Interactions

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. Consider therapy modification

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

BCRP/ABCG2 Substrates: Eltrombopag may increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

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. Consider therapy modification

CycloSPORINE (Systemic): May decrease the serum concentration of Eltrombopag. Monitor therapy

Deferiprone: UGT1A6 Inhibitors may increase the serum concentration of Deferiprone. Avoid combination

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination

Eluxadoline: Eltrombopag may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with eltrombopag and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

OATP1B1/1B3 (SLCO1B1/1B3) Substrates: Eltrombopag may increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. 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. Consider therapy modification

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. 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; Canadian labeling recommends limiting rosuvastatin to a maximum of 20 mg/day. Consider therapy modification

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. 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 (if needed) of 50 mg when used with a BCRP inhibitor. Consider therapy modification

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

Adverse Reactions

>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)

Warnings/Precautions

Concerns related to adverse effects:

• Cataract formation: Cataract formation or worsening was observed in clinical trials. Monitor regularly for signs and symptoms of cataracts; obtain ophthalmic exam at baseline and during therapy. Use with caution in patients at risk for cataracts (eg, advanced age, long-term glucocorticoid use).
• Hepatotoxicity: [US Boxed Warning]: Eltrombopag may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended. Liver enzyme elevations may occur; for the treatment of chronic immune thrombocytopenia (ITP), chronic hepatitis C-associated thrombocytopenia, and refractory severe aplastic anemia, obtain ALT, AST, and bilirubin prior to treatment initiation, every 2 weeks during adjustment phase, then monthly (after stable dose established). For the first-line treatment of severe aplastic anemia, obtain ALT, AST, and bilirubin prior to therapy initiation, every other day (while hospitalized for immunosuppressive therapy), and then every 2 weeks during treatment. Eltrombopag inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinemia; obtain fractionation for elevated bilirubin levels. Repeat abnormal liver function tests within 3 to 5 days; if confirmed abnormal, monitor weekly until resolves, stabilizes, or returns to baseline. For the treatment of chronic ITP, chronic hepatitis C-associated thrombocytopenia, and refractory severe aplastic anemia, discontinue treatment for 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 progressively increasing, or persistent (≥4 weeks), or accompanied by increased direct bilirubin, or accompanied by clinical signs of liver injury or evidence of hepatic decompensation. Hepatotoxicity may recur with re-treatment after therapy interruption; however, if the benefit of treatment outweighs the hepatotoxicity risk, initiate carefully, and monitor liver function tests weekly during the dose adjustment phase. Permanently discontinue if liver test abnormalities persist, worsen, or recur with rechallenge. In clinical trials, isolated cases of severe liver injury occurred, liver function test abnormalities usually occurred ~3 months after initiation of eltrombopag and resolved with discontinuation. For the first-line treatment of severe aplastic anemia, withhold eltrombopag for ALT or AST >6 times ULN; reinitiate eltrombopag at a reduced dose when ALT or AST return to acceptable levels.
• Thromboembolism: Thromboembolism (venous or arterial) may occur with excessive increases in platelet levels. Use with caution in patients with known risk factors for thromboembolism (eg, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome, chronic liver disease). Thrombotic events, primarily involving the portal venous system, were more commonly seen in eltrombopag-treated chronic hepatitis C patients 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: [US Boxed Warning]: 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. If antiviral therapy is discontinued for hepatic decompensation according to interferon/ribavirin recommendations, eltrombopag should also be discontinued. 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.
• Hepatic impairment: Clearance may be reduced in patients with hepatic impairment; use with caution; reduced starting doses are recommended in patients with ITP (except children 1 to 5 years) and severe aplastic anemia who have hepatic impairment (no initial dose reductions are necessary in patients with chronic hepatitis C-related thrombocytopenia).
• 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 alone in patients with intermediate-1, intermediate-2, or high-risk MDS was terminated due to lack of efficacy and safety concerns (including increased progression to AML). Increased relative risks of death and progression to AML in the eltrombopag arm compared to placebo were observed in the study.
• Renal impairment: Use with caution with renal impairment (any degree) and monitor closely; initial dosage adjustment is not necessary.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Asian ethnicity (eg, Chinese, Japanese, Korean, Taiwanese, Thai): May have greater drug exposure (compared to non-Asians); therapy should be initiated with lower starting doses in ITP and severe aplastic anemia patients.

Other warnings/precautions:

• Appropriate use: Do not use to normalize platelet counts. ITP: Indicated only when the degree of thrombocytopenia and clinical conditions increase the risk for bleeding in patients with chronic ITP; use the lowest dose necessary to achieve and maintain platelet count ≥50,000/mm³. Discontinue if platelet count does not respond to a level to avoid clinically important bleeding after 4 weeks at the maximum recommended dose. Chronic hepatitis C-associated thrombocytopenia: Use only when thrombocytopenia prevents the initiation and maintenance of interferon-based therapy; discontinue if antiviral therapy is discontinued. Safety and efficacy have not been established when combined with direct acting antiviral medications approved for chronic hepatitis C genotype 1 infection therapy. Severe refractory aplastic anemia: Use the lowest dose to achieve and maintain hematologic response. Discontinue if no hematologic response has occurred after 16 weeks of therapy, excessive platelet count responses or important liver test abnormalities. Consider discontinuation if new cytogenetic abnormalities are observed.

Monitoring Parameters

Chronic ITP, chronic hepatitis C-associated thrombocytopenia, and severe refractory aplastic anemia: Monitor liver function tests, including ALT, AST, and bilirubin (baseline, every 2 weeks during dosage titration, then monthly after a stable dose is achieved; evaluate abnormal liver function tests within 3 to 5 days; monitor weekly until abnormalities resolve, stabilize, or return to baseline or if re-treating [not recommended] after therapy interruption for hepatotoxicity); bilirubin fractionation (for elevated bilirubin)

Thrombocytopenia due to CHC and chronic ITP: CBC with differential and platelet count (weekly at initiation and during dosage titration, 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).

Severe aplastic anemia, first-line treatment: 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; CBC with differential and platelets (regularly throughout therapy)

Severe aplastic anemia, refractory: CBC with differential and platelets (regularly throughout therapy)

Monitor regularly for signs and symptoms of cataracts; obtain ophthalmic exam at baseline and during therapy. Monitor for signs/symptoms of thromboembolism. Monitor adherence.

Pregnancy

Pregnancy Considerations

Information related to the use of eltrombopag for the treatment of thrombocytopenia in pregnancy is limited (Favier 2018; Purushothaman 2016; Suzuki 2018).

Females of reproductive potential 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 and pregnancy and/or contraception should be followed. Refer to the ribavirin monograph for additional information.

Patient Education

What is this drug used for?

• It is used to raise platelet counts.
• It is used to treat immune thrombocytopenia (ITP).
• It is used to treat aplastic anemia.

Frequently reported side effects of this drug

• Headache
• Nausea
• Vomiting
• Diarrhea
• Mouth pain
• Abdominal pain
• Fatigue
• Trouble sleeping
• Itching
• Lack of appetite
• Flu-like symptoms
• Cough
• Muscle pain
• Joint pain
• Common cold symptoms
• Dizziness
• Sore throat
• Nose irritation
• Tooth pain
• Muscle spasms
• Skin discoloration
• Hair loss

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood.
• Severe loss of strength and energy
• Vision changes
• Eye pain
• Severe eye irritation
• Bruising
• Bleeding
• Confusion
• Swelling of arms or legs
• Chills
• Abdominal swelling
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.