preserving [50,000/mm:<150,000/mm 3 . 1 If the platelet count is persistently elevated (e.g., >400,000/mm 3 after 2 weeks at the lowest dosage), discontinue eltrombopag permanently. 1 Prescribing Limits Adults Idiopathic Thrombocytopenic Purpura Oral Maximum daily dosage: 75 mg. 1 Do not give more often than once daily. 1 Special Populations Hepatic Impairment In patients with moderate or severe hepatic impairment, decrease initial dosage to 25 mg daily. 1 8 9 (See Hepatotoxicity under Cautions and also Laboratory Monitoring under Cautions.) East Asian Ancestry In patients of East Asian ancestry (e.g., Chinese, Japanese, Taiwanese, Korean), decrease initial dosage to 25 mg daily. 1 (See East Asian Ancestry under Cautions.) Cautions for Eltrombopag Contraindications The manufacturer states that there are no known contraindications to the use of eltrombopag. 1 Warnings/Precautions Warnings Hepatotoxicity Risk of hepatic and biliary impairment. 1 Abnormalities in serum ALT, AST, and bilirubin concentrations, predominantly grade 2 or less in severity, reported. 1 Grade 4 elevations in serum liver enzymes, as well as worsening of underlying cardiopulmonary disease and subsequent death, reported in one patient. 1 Discontinue eltrombopag if serum ALT levels increase to ≥3 times the ULN and are progressive, persistent (≥4 weeks), or are accompanied by an increased direct bilirubin concentration or clinical symptoms of hepatotoxicity or hepatic decompensation. 1 (See Laboratory Monitoring under Cautions.) Retreatment with eltrombopag after discontinuance for hepatotoxicity is not recommended. 1 However, may consider retreatment if the anticipated clinical benefit of eltrombopag outweighs the potential risk of hepatotoxicity. 1 If treatment is reinitiated, evaluate serum ALT, AST, and bilirubin concentrations weekly during the dosage adjustment phase. 1 If abnormal liver function tests persist, worsen, or recur, permanently discontinue eltrombopag. 1 General Precautions Bone Marrow Reticulin Deposition and Bone Marrow Fibrosis Thrombopoietin (TPO)-receptor agonists increase the risk of development or progression of reticulin fiber deposition within the bone marrow, thereby increasing the risk for bone marrow fibrosis or myelofibrosis. 1 Risk for bone marrow fibrosis with cytopenias in patients receiving eltrombopag not excluded in clinical studies. 1 Evaluate a peripheral blood smear prior to starting eltrombopag therapy and monthly thereafter once a stable dosage has been achieved. 1 Examination of the peripheral blood smear should include establishment of a baseline level of cellular morphologic abnormalities; monthly evaluations should include examinations for new or worsening morphologic abnormalities (e.g., teardrop or nucleated erythrocytes, immature leukocytes). 1 Perform CBC monthly to evaluate new or worsening cytopenias. 1 If a new or worsening morphologic abnormality or cytopenia develops, discontinue eltrombopag and consider a bone marrow biopsy, with additional staining for fibrosis. 1 Thrombocytopenia and Hemorrhage Following Eltrombopag Discontinuance Risk of thrombocytopenia, which may be more severe than prior to therapy, after discontinuance of eltrombopag. 1 May result in increased risk of bleeding, especially if eltrombopag is discontinued while the patient is receiving concomitant antiplatelet or anticoagulation therapy. 1 Transient decrease in platelet count to levels lower than baseline reported in clinical studies following discontinuance of eltrombopag. 1 Serious hemorrhagic events occurring within 1 month of discontinuance of eltrombopag and requiring the use of additional ITP therapy also reported in patients with severe thrombocytopenia in clinical studies. 1 Perform CBC with platelet count weekly for at least 4 weeks following discontinuance of eltrombopag. 1 Consider additional ITP therapy for worsening thrombocytopenia. 1 Thrombosis/Thromboembolism Risk of thrombosis or a thromboembolic complication as a result of excessive increase in platelet count secondary to excessive dosages of eltrombopag or medication errors resulting in excessive dosages. 1 Thrombosis also may occur even with normal or low platelet counts. 7 Use eltrombopag with caution in patients with known risk factors for thromboembolism (e.g., factor V Leiden, antithrombin III [ATIII] deficiency, antiphospholipid syndrome). 1 To minimize the risk for a thrombotic or thromboembolic complication, do not use eltrombopag to normalize platelet counts; use drug only to maintain a platelet count of ≥50,000/mm 3 according to the dosage adjustment guidelines. 1 8 9 (See Idiopathic Thrombocytopenic Purpura under Dosage and Administration.) Thrombosis of the portal venous system reported in patients with chronic liver disease receiving eltrombopag. 8 9 Platelet counts >200,000/mm 3 observed in some patients who received eltrombopag and experienced portal venous thrombosis. 8 9 Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease. 8 9 Malignancy Possible risk of progression to a hematologic malignancy, especially in patients with myelodysplastic syndrome (MDS), secondary to stimulation of the TPO receptor present on the surface of hematopoietic cells by eltrombopag. 1 Do not use eltrombopag to treat or correct thrombocytopenia related to an underlying hematologic cause (e.g., myelodysplasia) or resulting from chemotherapy; use eltrombopag only for thrombocytopenia associated with chronic ITP. 1 Cataracts Development or worsening of cataracts reported. 1 Perform a baseline ocular examination prior to eltrombopag therapy; while on therapy, monitor periodically for signs and symptoms of cataracts. 1 Laboratory Monitoring Obtain CBC, including platelet count and peripheral blood smear, prior to starting therapy, weekly during the dosage adjustment phase, then monthly once a stable dosage has been achieved. 1 Baseline peripheral blood smears should establish the presence and extent of red and white cell abnormalities. 1 Once eltrombopag is discontinued, evaluate CBC with platelet count weekly for at least 4 weeks to monitor for worsening thrombocytopenia. 1 Evaluate serum ALT, AST, and bilirubin concentrations prior to starting therapy and every 2 weeks during the dosage adjustment phase, then monthly once a stable dosage has been achieved. 1 If serum bilirubin is elevated, also obtain a fractionated bilirubin concentration. 1 In patients who develop liver function test abnormalities, repeat these tests within 3 5 days to confirm the results; if an abnormality is confirmed, monitor liver function tests weekly until the abnormality resolves, stabilizes, or returns to baseline. 1 Discontinue eltrombopag therapy if important hepatic abnormalities occur. 1 (See Hepatotoxicity under Cautions.) Specific Populations Pregnancy Category C. 1 Pregnancy registry at 888-825-5249. 1 Lactation Not known whether eltrombopag is distributed into human milk. 1 Discontinue nursing or the drug. 1 Pediatric Use Safety and efficacy not established in pediatric patients> <18 years of age. 1 7 Geriatric Use No substantial differences in safety and efficacy in geriatric patients ≥65 years of age relative to younger adults, but increased sensitivity cannot be ruled out. 1 Hepatic Impairment Decreased clearance; exercise caution, adjust dosage, and monitor closely in patients with moderate or severe hepatic impairment. 1 8 9 (See Hepatic Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.) Thrombosis of the portal venous system reported in patients with thrombocytopenia and chronic liver disease receiving eltrombopag. 8 9 (See Thrombosis/Thromboembolism under Cautions.) Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease. 8 9 To minimize the risk for a thrombotic or thromboembolic complication, do not use eltrombopag to normalize platelet counts; only use the drug to maintain a platelet count of ≥50,000/mm 3 according to the dosage adjustment recommendations. 1 8 9 (See Dosage under Dosage and Administration.) Renal Impairment Safety and efficacy of eltrombopag in patients with varying degrees of impaired renal function have not been established. 1 Closely monitor patients with impaired renal function. 1 East Asian Ancestry Increased eltrombopag exposure reported in patients of East Asian ancestry (e.g., Chinese, Japanese, Taiwanese, Korean); dosage adjustment recommended. 1 Somewhat increased (but qualitatively similar) pharmacodynamic response also reported. 1 (See East Asian Ancestry under Dosage and Administration and also see Special Populations under Pharmacokinetics.) Common Adverse Effects Nausea, 1 vomiting, 1 menorrhagia, 1 myalgia, 1 paresthesia, 1 cataract, 1 dyspepsia, 1 ecchymosis, 1 thrombocytopenia, 1 increased serum transaminases (ALT, AST), 1 conjunctival hemorrhage. 1 In an extension study: headache, upper respiratory tract infection, diarrhea, nasopharyngitis. 5 Interactions for Eltrombopag Metabolized by CYP1A2 and CYP2C8; also undergoes glucuronidation by UGT isoenzymes 1A1 and 1A3. 1 Inhibits CYP2C8 and CYP2C9 and the organic anion-transporting polypeptide (OATP) 1B1. 1 Drugs Affecting Hepatic Microsomal Enzymes Moderate to strong inhibitors of CYP1A2 or CYP2C8: potential pharmacokinetic interaction (increased systemic exposure to eltrombopag). 1 Use with caution. 1 Moderate to strong inducers of CYP1A2 or CYP2C8: potential pharmacokinetic interaction (decreased systemic exposure to eltrombopag). 1 Drugs Metabolized by Hepatic Microsomal Enzymes Substrates of CYP2C8 or CYP2C9: potential pharmacokinetic interaction (altered metabolism of CYP2C8 or CYP2C9 substrates). 1 Inhibition or induction of the metabolism of a combination of probe substrates for CYP1A2, CYP2C19, CYP2C9, or CYP3A4) following administration of eltrombopag (75 mg once daily) for 7 days to healthy male individuals not demonstrated. 1 Probe substrates for CYP2C8 not evaluated. 1 Drugs Transported by Organic Anion-transporting Polypeptide 1B1 Substrates of organic anion-transporting polypeptide (OATP) 1B1: Potential pharmacokinetic interaction (increased concentrations of concomitantly administered OATP1BI substrates. 1 Consider reduction of OATP1B1 substrate dosage if manifestations of excessive systemic exposure to these drugs occur. 1 Drugs Affecting or Metabolized by Uridine Diphosphate-glucuronosyltransferase (UGT) Eltrombopag inhibits uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, and 2B15. 1 Substrates of UGTs: Potential pharmacokinetic interaction (increased systemic exposure to multiple UGT substrates. 1 Use with caution. 1 Moderate to strong inhibitors of UGT1A1 or UGT1A3: Potential pharmacokinetic interaction (increased systemic exposure to eltrombopag). 1 Use with caution. 1 Specific Drugs and Foods Drug Interaction Comments Acetaminophen Potential increased systemic exposure to acetaminophen 1 Use with caution 1 Benzylpenicillin Potential increased benzylpenicillin concentrations 1 Consider reduction of benzylpenicillin dosage if manifestations of excessive systemic exposure occur 1 Caffeine Pharmacokinetics of caffeine unlikely to be affected 1 Cations, polyvalent (e.g., iron, calcium, aluminum, magnesium, selenium, zinc) found in food, mineral supplements, and antacids Reduced plasma eltrombopag concentration in patients receiving concomitant antacid therapy containing aluminum hydroxide, magnesium carbonate, and sodium alginate 1 4 Reduced eltrombopag AUC reported in association with high-calcium, high-fat breakfast 4 Avoid medications and foods containing polyvalent cations, including antacids, dairy products, and mineral supplements, for 4 hours before and after each dose of eltrombopag 1 4 Ciprofloxacin Potential increased systemic exposure to eltrombopag 1 Use with caution 1 Flurbiprofen Pharmacokinetics of flurbiprofen unlikely to be affected 1 Fluvoxamine Potential increased systemic exposure to eltrombopag 1 Use with caution 1 Gemfibrozil Potential increased systemic exposure to eltrombopag 1 Use with caution 1 HMG-CoA reductase inhibitors (statins; e.g., atorvastatin, fluvastatin, pravastatin, rosuvastatin) Potential increased statin concentrations 1 Increased AUC and peak plasma concentration of rosuvastatin reported following administration of single 10-mg dose of rosuvastatin in healthy adults receiving 75 mg of eltrombopag daily for 5 days 1 Consider reduction of statin dosage if manifestations of excessive systemic exposure occur 1 Reduction in rosuvastatin dosage by 50% was recommended for patients receiving concomitant eltrombopag in clinical trials 1 Meglitinides (nateglinide, repaglinide) Potential increased meglitinide concentrations 1 Consider reduction of meglitinide dosage if manifestations of excessive systemic exposure occur 1 Methotrexate Potential increased methotrexate concentrations 1 Consider reduction of methotrexate dosage if manifestations of excessive systemic exposure occur 1 Midazolam Pharmacokinetics of midazolam unlikely to be affected 1 NSAIAs Potential increased systemic exposure to NSAIAs 1 Use with caution 1 Omeprazole Potential decreased systemic exposure to eltrombopag; pharmacokinetics of omeprazole unlikely to be affected 1 Opiates Potential increased systemic exposure to opiates 1 Use with caution 1 Rifampin Potential decreased systemic exposure to eltrombopag 1 Potential increased rifampin concentrations 1 1 Consider reduction of rifampin dosage if manifestations of excessive systemic exposure occur 1 Tobacco Potential decreased systemic exposure to eltrombopag 1 Trimethoprim Potential increased systemic exposure to eltrombopag 1 Use with caution 1 Eltrombopag Pharmacokinetics Absorption Bioavailability Peak plasma concentrations occur 2 6 hours following oral administration. 1 Bioavailability of at least 52% reported following a single dose of 75 mg as an oral solution. 1 Onset Increases in platelet counts generally observed within 1 2 weeks after beginning therapy. 1 Duration Decreases in platelet counts generally observed within 1 2 weeks after discontinuance of therapy. 1 Food Food (standard high-fat breakfast) decreases rate and extent of absorption; 1 calcium content of meal may contribute to decreased absorption. 1 4 Distribution Extent Distributes into blood cells; concentrations in blood cells about 50 79% of plasma concentrations. 1 Not known whether eltrombopag is distributed into human milk. 1 Plasma Protein Binding >99%. 1 Elimination Metabolism Extensively metabolized, predominantly through pathways including cleavage, oxidation (CYP1A2 and CYP2C8), and conjugation with glucuronic acid (via UGT1A1 and UGT1A3), glutathione, or cysteine. 1 Metabolites associated with glucuronidation and oxidation detected. 1 Elimination Route Excreted in feces (59%) and urine (31%). 1 Unchanged drug excreted in feces accounts for 20% of the dose; no unchanged drug detectable in urine. 1 Half-life Healthy individuals: 21 32 hours. 1 Patients with ITP: 26 35 hours. 1 Special Populations Compared with healthy individuals, the AUC for eltrombopag was 41% higher in patients with mild hepatic impairment and 80 93% higher in patients with moderate to severe hepatic impairment. 1 A corresponding reduction (50%) in apparent clearance of eltrombopag was reported in patients with moderate or severe hepatic impairment. 1 Prolonged half-life (twofold) of eltrombopag also reported in patients with moderate or severe hepatic impairment. 1 High interpatient variability observed in the impact of hepatic impairment on eltrombopag pharmacokinetics. 1 Increased eltrombopag exposure (approximately 70%) reported in some Asian individuals of Japanese, Chinese, Taiwanese, and Korean ancestry (i.e., East Asian) with ITP as compared with non-Asian subjects (who were predominantly Caucasian). 1 Increased eltrombopag exposure (approximately 40%) reported in healthy African-American individuals in at least one clinical pharmacology study. 1 Clinical importance unknown. 1 Increased apparent eltrombopag clearance (about 27%) after adjustment for body weight difference reported in males compared with females. 1 Stability Storage Oral Tablets 25 C (may be exposed to 15 30 C). 1 Actions Eltrombopag olamine is a small-molecule, nonpeptide, thrombopoietin (TPO)-receptor agonist. 1 2 3 Interacts with the transmembrane domain of the TPO receptor, initiating a cascade of intracellular signaling events leading to proliferation and differentiation of bone marrow progenitor cells within the megakaryocytic lineage and subsequently increasing the production of platelets. 1 2 3 Eltrombopag (up to 150 mg daily for 5 days) did not prolong QT or QT corrected for rate (QT c ) interval in healthy adults. 1 Advice to Patients Importance of understanding that treatment can only be prescribed by a clinician registered with the PROMACTA CARES program; all ITP patients receiving eltrombopag must be enrolled in the PROMACTA CARES program. 1 7 (See Restricted Distribution under Dosage and Administration.) Under the REMS program approved by FDA, medication guide must be dispensed with every prescription for the drug. 10 Importance of carefully reading patient information (medication guide) provided by the manufacturer before initiating therapy, and each time prescription is refilled. 1 7 Importance of informing patients that risks associated with long-term administration of eltrombopag are not known. 1 Importance of understanding the goal of therapy is to achieve and maintain a platelet count of ≥50,000/mm 3 to reduce the risk of bleeding, not to normalize platelet count. 1 7 Risk of hepatic failure; importance of immediately reporting symptoms suggestive of jaundice (e.g., yellowing of skin or eyes), unusual darkening of urine, unusual fatigue, or right-upper quadrant (i.e., stomach area) pain to clinician. 1 7 Risk of worsening thrombocytopenia with possible bleeding shortly following discontinuance of eltrombopag, compared with such risks prior to starting therapy; increased risk if receiving concomitant anticoagulant or antiplatelet drugs. 1 7 Risk of reticulin fiber formation in bone marrow with possible progression to bone marrow fibrosis. 1 7 Increased risk of thrombosis or thromboembolism with high platelet counts resulting from excessive eltrombopag dosage. 1 7 Risk of thrombosis even with normal or low platelet counts. 7 Importance of immediately reporting symptoms suggestive of thrombosis (e.g., swelling, pain, or tenderness in leg) to clinician. 7 Increased risk of developing a hematologic malignancy, especially in patients with myelodysplastic syndrome (MDS). 1 7 Importance of avoiding situations or medications that may increase risk of bleeding. 1 7 Risk of new or worsened cataracts. 1 7 Importance of taking eltrombopag on an empty stomach (i.e., 1 hour before or 2 hours after a meal). 1 7 Importance of avoiding foods, supplements, and drugs that contain polyvalent cations (e.g., iron, calcium, aluminum, magnesium, selenium, zinc) for 4 hours before and after taking eltrombopag. 1 7 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses. 1 7 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 7 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Distribution of eltrombopag is restricted. 1 Eltrombopag Olamine Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablet 25 mg (of eltrombopag) Promacta GlaxoSmithKline 50 mg (of eltrombopag) Promacta GlaxoSmithKline 75 mg (of eltrombopag) Promacta GlaxoSmithKline AHFS DI Essentials. Copyright 2017, Selected Revisions April 6, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. GlaxoSmithKline. Promacta (eltrombopag) tablets prescribing information. Research Triangle Park, NC; 2009 Oct. 2. Bussel JB, Cheng G, Saleh MN et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med . 2007; 357:2237-47. [PubMed 18046028] 3. Bussel JB, Provan D, Shamsi T et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet . 2009; 373:641-8. [PubMed 19231632] 4. Williams DD, Peng B, Bailey CK et al. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: Two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther . 2009; 31:764-76. [PubMed 19446149] 5. Bussel JB, Cheng G, Saleh MN et al. Safety and efficacy of long-term treatment with oral eltrombopag for chronic idiopathic thrombocytopenic purpura. Blood . 2008; 112: Abstract 3420. 6. Fogarty PF, Bussel JB, Cheng G et al. Oral eltrombopag treatment reduces the need for concomitant medications in patients with chronic idiopathic thrombocytopenic purpura. Blood . 2008; 112: Abstract 3424. 7. GlaxoSmithKline. Promacta (eltrombopag) tablets medication guide. Research Triangle Park, NC; 2010 Mar. 8. Food and Drug Administration. Promacta (eltrombopag): portal venous system thromboses in study of patients with chronic liver disease. Rockville, MD; May 12, 2010. From FDA website. 9. Aivado M. Dear healthcare professional letter: Promacta (eltrombopag) notification of safety information: portal venous system thromboses in a study of patients with chronic liver disease (ELEVATE). Collegeville, PA: GlaxoSmithKline; 2010 May 4. From FDA website. 10. GlaxoSmithKline. Promacta (eltrombopag) NDA 22-291 proposed risk evaluation and mitigation strategy (REMS). Collegeville, PA; 2010 Jun 10. Available from FDA website. Accessed 2010 Nov 24. Next Interactions Print this page Add to My Med List More about eltrombopag Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 5 Reviews Add your own review/rating Drug class: platelet-stimulating agents Consumer resources Eltrombopag Eltrombopag Tablets Eltrombopag (Advanced Reading) Professional resources Eltrombopag (Wolters Kluwer) Other brands: Promacta Related treatment guides Idiopathic Thrombocytopenic Purpura Aplastic Anemia Thrombocytopenia Thrombocytopenia Idiopathic> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Platelet-stimulating agents Related Drugs Idiopathic Thrombocytopenic Purpura prednisone , triamcinolone , dexamethasone , Decadron , Deltasone , cortisone , More... Aplastic Anemia Promacta , Leukine , Atgam , sargramostim , lymphocyte immune globulin, anti-thy (equine) , More... Thrombocytopenia Idiopathic triamcinolone , Promacta , Kenalog-40 , More... Thrombocytopenia prednisone , dexamethasone , Decadron , Deltasone , Promacta , More... Eltrombopag Rating 5 User Reviews 8.0 /10 5 User Reviews 8.0 Rate it!} } most desirable
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