eltrombopag

Therapeutic Classification: antithrombocytopenics

Pharmacologic Classification: thrombopoietin receptor agonists

REMS

Persistent or chronic immune thrombocytopenic in patients who have had an inadequate response to corticosteroids, immunoglobulins or splenectomy (should only be used in patients with an ↑ risk of bleeding).
Thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy.
Severe aplastic anemia in patients who have had an inadequate response to immunosuppressive therapy.
First-line treatment of severe aplastic anemia (in combination with standard immunosuppressive therapy).

Increases platelet production by initiating proliferation and differentiation of megakaryocytes from bone marrow progenitor cells.

Therapeutic effects:

Increased blood counts.

Absorption: 52% absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Extensively metabolized; 59% eliminated in feces, 20% as unchanged drug; 31% excreted in urine as metabolites.

Half-Life: 21–35 hr.

(effect on platelet count)

ROUTE	ONSET	PEAK	DURATION
PO	1 wk	2 wk	1 wk

Contraindicated in:

Lactation: Lactation.

Use Cautiously in:

Myelodysplastic syndromes (may ↑ risk of hematologic malignancy);
Hepatic impairment (lower initial dose required);
Patients of East-/Southeast-Asian ancestry (may require lower doses);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Children <1 yr (safety and effectiveness not established);
Geri: Older adults may be more sensitive to drug effects; ↑ dose cautiously, consider age-related ↓ in renal and hepatic function, concurrent disease states and drug therapy.

CV: THROMBOEMBOLISM

EENT: development/worsening of cataracts

GI: HEPATOTOXICITY

Drug-drug:

↓availability and absorption of iron, calcium, aluminum, magnesium, seleniumand zinc by chelation; give eltrombopag ≥2 hr before or 4 hr after medications containing these and other polyvalent cations.
Concomitant use with ribavirin and interferon may ↑ risk of hepatic decompensation

Drug-Food:

↓availability and absorption of iron, calcium, aluminum, magnesium, selenium, and zinc by chelation; do not administer within 4 hr of foods containing these and other polyvalent cations.

Persistent or Chronic Immune Thrombocytopenia

PO (Adults and Children ≥6 yr): 50 mg once daily, may be ↑ to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 75 mg/day); Patients of East-/Southeast-Asian ancestry—25 mg once daily initially, may be ↑ to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 75 mg/day).
PO (Children 1–5 yr): 25 mg once daily, may be ↑ to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 75 mg/day).

Hepatic Impairment

(Adults ): Mild, moderate, or severe hepatic impairment (Child Pugh Class A, B, C): 25 mg once daily initially, may be ↑ to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 75 mg/day);Patients of East-/Southeast-Asian ancestry with mild, moderate, or severe hepatic impairment (Child Pugh Class A, B, C)—12.5 mg once daily initially, may be ↑ to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 75 mg/day).

Chronic Hepatitis C-Associated Thrombocytopenia

PO (Adults ): 25 mg once daily; may be ↑ by 25 mg every 2 wk to achieve the target platelet count required to initiate antiviral therapy; during antiviral therapy, adjust dose to avoid dose ↓ of peginterferon (not to exceed 100 mg/day) .

First-Line Treatment of Severe Aplastic Anemia

PO (Adults and Children ≥12 yr): 150 mg once daily for 6 mo; Patients of East-/Southeast-Asian ancestry—75 mg once daily for 6 mo.
PO (Children 6–11 yr): 75 mg once daily for 6 mo; Patients of East-/Southeast-Asian ancestry—37.5 mg once daily for 6 mo.
PO (Children 2–5 yr): 2.5 mg/kg once daily for 6 mo; Patients of East-/Southeast-Asian ancestry—1.25 mg/kg once daily for 6 mo.

Hepatic Impairment

PO (Adults and Children ≥12 yr): Mild, moderate, or severe hepatic impairment (Child Pugh Class A, B, C): 75 mg once daily for 6 mo.

Hepatic Impairment

PO (Adults and Children 6–11 yr): Mild, moderate, or severe hepatic impairment (Child Pugh Class A, B, C): 37.5 mg once daily for 6 mo.

Hepatic Impairment

PO (Adults and Children 2–5 yr): Mild, moderate, or severe hepatic impairment (Child Pugh Class A, B, C): 1.25 mg/kg once daily for 6 mo.

Refractory Severe Aplastic Anemia

PO (Adults ): 50 mg once daily; may be ↑ by 50 mg every 2 wk to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 150 mg/day);Patients of East-/Southeast-Asian ancestry—25 mg once daily; may be ↑ by 50 mg every 2 wk to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 150 mg/day).

Hepatic Impairment

(Adults ): Mild, moderate, or severe hepatic impairment (Child Pugh Class A, B, C): 25 mg once daily; may be ↑ by 50 mg every 2 wk to achieve a platelet count of ≥50 × 10⁹/L (not to exceed 150 mg/day).

Powder for oral suspension: 12.5 mg/pkt; 25 mg/pkt
Tablets: 12.5 mg; 25 mg; 50 mg; 75 mg

Monitor for unusual bleeding and bruising, thromboembolic events (deep vein thrombosis, pulmonary embolus, stroke, myocardial infarction) and signs of hepatotoxicity during therapy. If thromboembolic events occur, discontinue eltrombopag but continue horse antithymocyte globulin (h-ATG) and cyclosporine.
Monitor for signs and symptoms of cataracts. Perform baseline ocular examination prior to administration and periodically during therapy.

Lab Test Considerations:

For Chronic Immune Thrombocytopenia: Monitor CBC with differential and platelet count weekly until platelet count is stable. Goal is platelet count ≥50 × 10⁹/L. Modify dose based on platelet count. If platelet count <50 × 10⁹/L following at least 2 wk of therapy, ↑ daily dose by 25 mg; maximum 75 mg/day. For patients taking 12.5 mg once daily, ↑ dose to 25 mg daily before ↑ dose by 25 mg. If platelet count is ≥200 × 10⁹/L to ≤400 × 10⁹/L,↓ dose by 25 mg. For patients taking 25 mg/day, ↓ dose to 12.5 mg/day. Wait 2 wk to assess effects of dose adjustment. If platelet count >400 × 10⁹/L, stop eltrombopag, ↑ monitoring of platelet to twice weekly. Once platelet count is <150 × 10⁹/L, reinitiate therapy at dose reduced by 25 mg/day. For patients taking 25 mg/day, reinitiate at dose of 12.5 mg/day.If platelet count >400 × 10⁹/L after 2 wk of therapy at lowest dose, permanently discontinue eltrombopag. Discontinue eltrombopag if platelet count does not ↑ to a level sufficient to avoid clinically important bleeding after 4 wk of therapy at maximum daily dose of 75 mg.
- Chronic Hepatitis C-Associated ThrombocytopeniaMonitor platelet counts every wk prior to starting antiviral therapy. Goal is to achieve and maintain platelet count necessary to initiate and maintain antiviral therapy with pegylated interferon and ribavirin. Modify dose based on platelet count. Adjust dose in 25-mg increments every 2 wks as necessary for target platelet count required to initiate antiviral therapy. During antiviral therapy, adjust dose to avoid dose reductions of peginterferon. Monitor CBC with differentials, including platelet counts, weekly during antiviral therapy until stable platelet count is achieved. Monitor platelet counts monthly thereafter. If platelet count <50 × 10⁹/L following at least 2 wk of therapy, ↑ daily dose by 25 mg; maximum 100 mg/day. If platelet count is ≥200 × 10⁹/L to ≤400 × 10⁹/L,↓ dose by 25 mg. Wait 2 wk to assess effects of dose adjustment. If platelet count >400 × 10⁹/L, stop eltrombopag, ↑ monitoring of platelet to twice weekly. Once platelet count is <150 × 10⁹/L, reinitiate therapy at dose reduced by 25 mg/day. For patients taking 25 mg/day, reinitiate at dose of 12.5 mg/day.If platelet count >400 × 10⁹/L after 2 wk of therapy at lowest dose, permanently discontinue eltrombopag. Discontinue eltrombopag when antiviral therapy is discontinued.
- Aplastic AnemiaGoal is platelet count >50 × 10⁹/L. Modify dose based on platelet count. If platelet count <50 × 10⁹/L following at least 2 wk of therapy, ↑ daily dose by 50 mg. If patient taking 25 mg/day, ↑ dose to 50 mg before increasing by 50 mg; maximum 150 mg/day. If platelet count is ≥200 × 10⁹/L to ≤400 × 10⁹/L,↓ dose by 50 mg. Wait 2 wk to assess effects of dose adjustment. If platelet count >400 × 10⁹/L, stop eltrombopag, for 1 wk. Once platelet count is <150 × 10⁹/L, reinititate therapy at dose ↓ by 50 mg/day. If platelet count >400 × 10⁹/L after 2 wk of therapy at lowest dose, permanently discontinue eltrombopag. If no hematologic response after 16 wks of therapy, discontinue therapy.
- When switching between oral suspension and tablet, assess platelet counts weekly for 2 wks, then follow standard monthly monitoring.
- Monitor AST, ALT, and serum bilirubin prior to therapy, every 2 wk during dose adjustment, and monthly following stable dose. If bilirubin is ↑, perform fractionation. Evaluate abnormal liver tests with repeat testing in 3–5 days. If abnormalities are confirmed, monitor serum liver tests weekly until resolved, stabilize, or return to baseline. Discontinue eltrombopag if ALT levels ≥3× upper limit of normal (ULN) in patients with normal liver function or ≥3× baseline or >5× ULN and progressively increasing, or persistent for ≥4 wk, or accompanied by ↑ direct bilirubin, or accompanied by symptoms of liver injury or hepatic decompensation.
- First line treatment of aplastic anemiaMeasure ALT, AST, and bilirubin before starting therapy, every other day while hospitalized for hATG therapy, and then every 2 wks during therapy. Do not start eltrombopag if AST or ALT levels ≥6 × upper limit of normal (ULN). If <5 × ULN, restart at same dose. If AST and ALT >6 × ULN after restarting, discontinue therapy and monitor ALT or AST at least every 3 to 4 days. If ALT or AST < 5 × ULN, restart eltrombopag at dose reduced from previous dose by 25 mg daily. If AST or ALT >6 × ULN with reduced dose, reduce dose by 25 mg until AST or ALT <5 × ULN. In pediatric patients under 12 yrs, reduce daily dose by ≥15% to nearest dose that can be administered.

PO: Administer on an empty stomach, or with a meal low in calcium (≤50 mg). DNC: Swallow tablets whole; do not crush, break, chew or mix with food/liquids.
- Prepare oral suspension with water only using 40-mL reconstitution vessel and threaded closure with syringe-port capability provided; do not use hot water to prepare the suspension. Powder for suspension is reddish-brown to yellow. Administer suspension immediately after preparation with single-use oral dosing syringe provided. Discard any suspension not administered within 30 minutes after preparation.
- Allow at least 4 hr between eltrombopag and other medications (antacids), calcium-rich foods (containing > 50 mg calcium [dairy products, calcium-fortified juices, certain fruits and vegetables]), and supplements containing polyvalent cations (iron, calcium, aluminum, magnesium, zinc, selenium).

Instruct patient to take eltrombopag as directed. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes. Explain purpose, risks and benefits of therapy to patient. Risks or long term therapy are unknown.
Instruct patient to avoid taking eltrombopag within 4 hr of foods, mineral supplements, and antacids containing iron, calcium, aluminum, magnesium, zinc, and selenium.
Advise patients to avoid activities and medications that may increase risk of bleeding.
Advise patient of need for baseline ocular exam before starting therapy and monitoring for signs and symptoms of cataracts during therapy.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Instruct patient to notify health care professional if symptoms of liver problems (yellowing of skin or whites of eyes, unusual darkening of urine, unusual tiredness, pain in right upper stomach, confusion, swelling of abdomen) occur.
Rep: May cause fetal harm. Advise females of reproductive potential use effective contraception during and for at least 7 days after therapy ended and to notify health care professional promptly if pregnancy is planned or suspected and to avoid breastfeeding.
Emphasize the importance of routine lab tests to determine effectiveness and monitor for side effects.

Increased platelet counts and decreased risk of bleeding. Platelet counts usually increase within 1–2 wk of starting and decrease within 1–2 wk of discontinuing therapy.
Increased blood counts. For patients with aplastic anemia, if no hematologic response after 16 wk of therapy, discontinue therapy

NDC Code

0078- Novartis Pharmaceuticals Corporation
- 0078-0684- PROMACTA
  - 0078-0684-15- 30 TABLET, FILM COATED in 1 BOTTLE (0078-0684-15)

0078- Novartis Pharmaceuticals Corporation
- 0078-0685- PROMACTA
  - 0078-0685-15- 30 TABLET, FILM COATED in 1 BOTTLE (0078-0685-15)

0078- Novartis Pharmaceuticals Corporation
- 0078-0686- PROMACTA
  - 0078-0686-15- 30 TABLET, FILM COATED in 1 BOTTLE (0078-0686-15)

0078- Novartis Pharmaceuticals Corporation
- 0078-0687- PROMACTA
  - 0078-0687-15- 30 TABLET, FILM COATED in 1 BOTTLE (0078-0687-15)

0078- Novartis Pharmaceuticals Corporation
- 0078-0972- PROMACTA
  - 0078-0972-61- 1 CARTON in 1 KIT (0078-0972-61) > 30 PACKET in 1 CARTON (0078-0972-23) > 1 POWDER, FOR SUSPENSION in 1 PACKET (0078-0972-19)

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