eltrombopag (Rx)

Brand and Other Names:Promacta
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 12.5mg
  • 25mg
  • 50mg
  • 75mg

Chronic Immune Thrombocytopenia (ITP)

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

Indicated to allow initiation and maintenance of interferon-based therapy

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

During antiviral therapy, adjust dose to avoid dose reductions of peginterferon

Severe Aplastic Anemia

First-line therapy

  • First-line treatment, in combination with standard immunosuppressive therapy, for patients with severe aplastic anemia (SAA)
  • Initial dose: 150 mg PO qDay for 6 months
  • Do not exceed initial dose; total duration is 6 months

Refractory SAA

  • Indicated for SAA in patients who fail to respond adequately to at least 1 prior immunosuppressive therapy
  • 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

Dosage Modifications

Dosage adjustment based on platelet count

  • Chronic ITP
    • Plt <50 x 10^9/L (following ≥2 weeks of treatment): Increase daily dose by 25 mg; not to exceed 75 mg/day
    • Plt 200 to 400 x 10^9/L at any time: Decrease daily dose by 25 mg; assess effects after 2 weeks
    • Plt >400 x 10^9/L: Withhold eltrombopag; monitor twice weekly; once Plt <150 x 10^9/L, resume and reduce daily dose by 25 mg; (if taking 25 mg qDay, resume with 12.5 mg qDay)
    • Plt >400 x 10^9/L (after 2 weeks at the lowest dose): Discontinue eltrombopag
  • Dosage adjustment in adults with thrombocytopenia due to chronic hepatitis C
    • Plt <50 x 10^9/L (following ≥2 weeks of treatment): Increase daily dose by 25 mg; not to exceed 100 mg/day
    • Plt 200 to 400 x 10^9/L at any time: Decrease daily dose by 25 mg; assess effects after 2 weeks
    • Plt >400 x 10^9/L: Withhold eltrombopag; monitor twice weekly; once Plt <150 x 10^9/L, resume and reduce daily dose by 25 mg; (if taking 25 mg qDay, resume with 12.5 mg qDay)
    • Plt >400 x 10^9/L (after 2 weeks at the lowest dose): Discontinue eltrombopag
  • First-line SAA
    • Plt >200 to 400 x 10^9/L: Decrease daily dose by 25 mg q2Weeks to lowest dose that maintains Plt≥50 x 10^9/L
    • Plt >400 x 10^9/L: Discontinue eltrombopag for 1 week; once Plt is <200 x 10^9/L, resume and reduce daily dose by 25 mg
  • Refractory SAA
    • Plt <50 x 10^9/L (following ≥2 weeks of treatment): Increase daily dose by 50 mg; not to exceed 150 mg/day; if taking 25 mg qDay, increase dose to 50 mg qDay before increasing dose amount by 50 mg
    • Plt 200 to 400 x 10^9/L at any time: Decrease daily dose by 50 mg; assess after 2 weeks
    • Plt >400 x 10^9/L: Withhold dose for 1 week; when Plt is <150 x 10^9/L, resume and reduce dose by 50 mg
    • Plt >400 x 10^9/L after 2 weeks at lowest dose: Discontinue treatment
    • For patients who achieve trilineage response (eg, transfusion independence) ≥8 weeks: Reduce dose by 50%
    • Plts remain stable after 8 weeks at reduced dose: Discontinue treatment and monitor blood counts
    • If Plts <30 x 10^9/L, hemoglobin <9 g/dL, or ANC <0.5 x 10^9/L, reinitiate at previous effective dose

Discontinue treatment

  • Chronic ITP: If Plt fails to respond to a level that avoids clinically important bleeding after 4 weeks at the maximum of 75 mg/day
  • Refractory SAA: No hematologic response occurred after 16 weeks of therapy OR consider if new cytogenetic abnormalities are observed

Elevated ALT/AST (First-line SAA)

  • Increase ALT/AST >6x ULN: Discontinue treatment; once ALT/AST <5x ULN, reinitiate at same dose
  • Increase ALT/AST >6x ULN (after reinitiation): Discontinue treatment and monitor ALT/AST at least q3-4 days; once ALT/AST <5x ULN, reinitiate and reduce daily dose by 25 mg of previous dose
  • If ALT/AST returns to >6x ULN on reduced dose, the reduce daily dose by 25 mg until ALT/AST <5x ULN

Thromboembolic events (First-line SAA)

  • Thromboembolic events (eg, deep vein thrombosis, pulmonary embolus, stroke, myocardial infarction): Discontinue eltrombopag, remain on horse antithymocyte globulin (h-ATG) and cyclosporine

Asian ancestry

  • Such as Chinese, Japanese, Taiwanese, or Korean
  • Chronic ITP: Reduce to 25 mg PO qDay
  • First-line therapy for SAA: Decrease initial dose by 50%

Hepatic impairment

  • Chronic hepatitis C-associated thrombocytopenia: No dosage adjustment necessary
  • Chronic ITP
    • Mild to severe (Child-Pugh Class A to C): Reduce to 25 mg PO qDay
    • Mild to severe (Child-Pugh Class A to C) and of Asian ancestry: Reduce to 12.5 mg PO qDay
    • Wait 3 weeks before increasing dose after initiation or after any subsequent dosing increase
  • SAA
    • First-line therapy for SAA: Mild to severe (Child-Pugh Class A to C): Decrease initial dose by 50%
    • Refractory SAA: Mild to severe (Child-Pugh Class A to C): Reduce to 25 mg qDay

Dosing Considerations

During therapy, assess complete blood cell counts (CBCs) weekly until a stable Plt is achieved; obtain CBCs with differentials, monthly thereafter

Measure ALT, AST, and bilirubin prior to initiation of therapy, every other day while hospitalized for horse antithymocyte globulin (h-ATG) therapy, and then every 2 weeks during treatment

Limitations of use

  • Not indicated for treatment of myelodysplastic syndrome (MDS)
  • Safety and efficacy not established in combination with direct-acting antiviral agents used without interferon for chronic hepatitis C infection

Dosage Forms & Strengths

tablet

  • 12.5mg
  • 25mg
  • 50mg
  • 75mg

powder for oral suspension

  • 12.5mg/unit-dose
  • 25mg/unit-dose

Chronic Immune Thrombocytopenia

Indicated for treatment of thrombocytopenia in adults and pediatric patients ≥1 yr with chronic immune (idiopathic) thrombocytopenia (ITP) with insufficient response to corticosteroids, immunoglobulins, or splenectomy; use only in patients with ITP whose clinical condition increases bleeding risk

<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

  • First-line treatment, in combination with standard immunosuppressive therapy, for of adult and pediatric patients ≥2 yr with severe aplastic anemia (SAA)
  • <2 years: Safety and efficacy not established
  • 2-5 years: 2.5 mg/kg qDay for 6 months initially
  • 6-11 years: 75 mg PO qDay for 6 months initially
  • ≥12 years: 150 mg PO qDay for 6 months initially
  • Do not exceed initial dose; total duration is 6 months

Dosage Modifications

Dosage adjustment based on platelets

  • Chronic ITP
    • Plt <50 x 10^9/L (following ≥2 weeks of treatment): Increase daily dose by 25 mg; not to exceed 75 mg/day
    • Plt 200 to 400 x 10^9/L at any time: Decrease daily dose by 25 mg; assess effects after 2 weeks
    • Plt >400 x 10^9/L: Withhold eltrombopag; monitor twice weekly; once Plt <150 x 10^9/L, resume and reduce daily dose by 25 mg; (if taking 25 mg qDay, resume with 12.5 mg qDay)
    • Plt >400 x 10^9/L (after 2 weeks at the lowest dose): Discontinue eltrombopag
  • First-line SAA
    • Plt >200 to 400 x 10^9/L: Decrease daily dose by 25 mg q2Weeks to lowest dose that maintains
    • Plt≥50 x 10^9/L; decrease dose by 12.5 mg in pts <12 years
    • Plt >400 x 10^9/L: Discontinue eltrombopag for 1 week; once Plt is <200 x 10^9/L, resume and reduce daily dose by 25 mg; decrease dose by 12.5 mg in pts <12 years

Discontinue treatment

  • Chronic ITP: If Plt fails to respond to a level that avoids clinically important bleeding after 4 weeks at the maximum of 75 mg/day

Elevated ALT/AST (First-line SAA)

  • Increase ALT/AST >6x ULN: Discontinue eltrombopag; once ALT/AST <5x ULN, reinitiate at same dose
  • Increase ALT/AST >6x ULN (after reinitiation): Discontinue treatment and monitor ALT/AST at least q3-4 days; once ALT/AST <5x ULN, reinitiate and reduce daily dose by 25 mg of previous dose
  • If ALT/AST returns to >6x ULN on reduced dose, the reduce daily dose by 25 mg until ALT/AST <5x ULN
  • Patients <12 years: Reduce daily dose by at least 15% to nearest dose that can be administered

Thromboembolic events (First-line SAA)

  • Thromboembolic events (eg, deep vein thrombosis, pulmonary embolus, stroke, myocardial infarction): Discontinue eltrombopag, remain on h-ATG and cyclosporine

Asian ancestry

  • Such as Chinese, Japanese, Taiwanese, or Korean
  • Chronic ITP: Reduce to 25 mg PO qDay
  • First-line SAA: Decrease initial dose by 50%

Hepatic impairment

  • Chronic ITP
    • Mild to severe (Child-Pugh Class A to C): Reduce to 25 mg PO qDay
    • Mild to severe (Child-Pugh Class A to C) and of Asian ancestry: Reduce to 12.5 mg PO qDay
    • Wait 3 weeks before increasing dose after initiation or after any subsequent dosing increase
  • First-line therapy for SAA
    • Mild to severe (Child-Pugh Class A to C)
    • 2-5 years: 1.25 mg/kg qDay for 6 months initially
    • 6-11 years: 37.5 mg PO qDay for 6 months initially
    • ≥12 years: 75 mg PO qDay for 6 months initially

Dosing Considerations

During therapy, assess complete blood cell counts (CBCs) weekly until a stable Plt is achieved; obtain CBCs with differentials, monthly thereafter

When switching between oral suspension and tablet, assess platelets weekly for 2 weeks, and then follow standard monthly monitoring

Limitations of use

  • Not indicated for treatment of myelodysplastic syndrome (MDS)
  • Safety and efficacy not established in combination with direct-acting antiviral agents used without interferon for chronic hepatitis C infection
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Interactions

Interaction Checker

and eltrombopag

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (Chronic ITP)

            Upper respiratory tract infection (7-17%)

            Nasopharyngitis (12%)

            >10% (Chronic Hepatitis C)

            Anemia (40%)

            Pyrexia (30%)

            Fatigue (28%)

            Headache (21%)

            Nausea (19%)

            Diarrhea (19%)

            Decreased appetite (18%)

            Influenza-like illness (18%)

            Insomnia (16%)

            Asthenia (16%)

            Cough (15%)

            Pruritus (15%)

            Chills (14%)

            Myalgia (12%)

            >10% (SAA)

            Increased ALT (29%)

            Increased AST (17%)

            Increased blood bilirubin (17%)

            Refractory SAA

            • Nausea (33%)
            • Fatigue (28%)
            • Cough (23%)
            • Diarrhea (21%)
            • Headache (21%)
            • Pain in extremity (19%)
            • Pyrexia (14%)
            • Dizziness (14%)
            • Oropharyngeal pain (14%)
            • Abdominal pain (12%)
            • Muscle spasms (12%)
            • Transaminases increased (12%)
            • Arthralgia (12%)
            • Rhinorrhea (12%)

            1-10% (Chronic ITP)

            Headache (10%)

            Nausea (4-9%)

            Cough (9%)

            Diarrhea (9%)

            Pyrexia (9%)

            Abdominal pain (8%)

            Oropharyngeal pain (8%)

            Toothache (6%)

            Vomiting (6%)

            Urinary tract infection (5%)

            Increased ALT (5-6%)

            Increased AST (4-5%)

            Myalgia (5%)

            Cataract (5%)

            Fatigue (5%)

            Rash (3-5%)

            Increased blood bilirubin (4%)

            Oropharyngeal pain (4%)

            Pharyngitis (4%)

            Rhinorrhea (4%)

            Hyperbilirubinemia (3%)

            Back pain (3%)

            Influenza (3%)

            Paresthesia (3%)

            1-10% (Chronic Hepatitis C)

            Alopecia (10%)

            Peripheral edema (10%)

            1-10% (SAA)

            Rash (8%)

            Skin discoloration including hyperpigmentation (5%)

            Refractory SAA

            • Rash (7%)
            • Hyperbilirubinemia (7%)
            • Cataract (2%)

            Postmarketing Reports

            Skin discoloration including hyperpigmentation and skin yellowing

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            Warnings

            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
            • Monitor hepatic function and discontinue dosing as recommended

            Contraindications

            None

            Cautions

            May increase risk of severe and potentially life-threatening hepatotoxicity (see Black Box Warnings); monitor liver function before and during therapy

            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
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            Pregnancy & Lactation

            Pregnancy

            Available data from published case reports and postmarketing experience with use in pregnant women are insufficient to assess any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Animal data

            • In animal reproduction and developmental toxicity studies, oral administration of eltrombopag to pregnant rats during organogenesis resulted in embryolethality and reduced fetal weights at maternally toxic doses
            • Effects were observed at doses resulting in exposures that were 6 times the human clinical exposure based on AUC in patients with chronic ITP at 75 mg/day, and 3 times the AUC in patients with chronic hepatitis C at 100 mg/day

            Contraception

            • Based on animal reproduction studies, fetal harm may occur when administered to a pregnant woman
            • Use effective contraception in sexually-active females of reproductive during treatment and for at least 7 days after stopping treatment

            Lactation

            No data available regarding presence of eltrombopag or metabolites in human milk, effects on breastfed child, or on milk production

            However, drug was detected in pups of lactating rats 10 days postpartum suggesting potential for transfer during lactation; due to potential for serious adverse reactions in a breastfed child from drug, breastfeeding is not recommended during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Small-molecule thrombopoietin (TPO)-receptor agonist that interacts with human TPO receptor transmembrane domain of human TPO-receptor & initiates signaling cascades that induce proliferation & differentiation of megakaryocytes from bone marrow progenitor cells

            Absorption

            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

            Distribution

            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

            Elimination

            Half-life: 26-35 hr (in patients with ITP)

            Excretion: Feces (59%); urine (31%)

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            Administration

            Oral Suspension Preparation

            Prior to use of oral suspension, ensure patients or caregivers receive training on proper dosing, preparation, and administration of oral suspension

            Prepare suspension with cool or cold water only

            Gently and slowly shake bottle back and forth for a least 20 seconds to mix thoroughly without foaming (ie, do not shake bottle hard)

            Liquid will be dark brown in color

            Transfer mixture into oral syringe

            Oral Administration

            Take on empty stomach 1 hr before or 2 hr after food

            Take foods/medication, calcium-rich foods, or supplements containing polyvalent cations (eg, calcium, iron, zinc, magnesium) 2 hr before or 4 hr after

            Do NOT administer more than 1 dose within a 24-hr period

            Oral suspension

            • Place oral syringe tip into the inside of the child’s cheek
            • Slowly push plunger down to administer entire dose

            Storage

            Powder for oral suspension or tablets: Store at room temperature between 68-77°F (20-25°C)

            Reconstituted oral suspension

            • Store for up to 30 minutes at room temperature between 68-77°F (20-25°C)
            • Discard mixture if not used within 30 minutes; do not throw down the drain
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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.