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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to usePROMACTA safely and effectively. See full prescribing information forPROMACTA. PROMACTA (eltrombopag) tablets, for oral usePROMACTA (eltrombopag) for oral suspensionInitial U.S. Approval: 2008 WARNING: RISK FOR HEPATIC DECOMPENSATION INPATIENTS WITH CHRONIC HEPATITIS C and RISK OFHEPATOTOXICITYSee full prescribing information for complete boxed warning.In patients with chronic hepatitis C, PROMACTA in combination withinterferon and ribavirin may increase the risk of hepatic decompensation.(5.1)PROMACTA may increase the risk of severe and potentially lifethreatening hepatotoxicity. Monitor hepatic function and discontinuedosing as recommended. (5.2)----------------------------RECENT MAJOR CHANGES-------------------------Dosage and Administration, Administration (2.4)4/2020----------------------------INDICATIONS AND USAGE--------------------------PROMACTA is a thrombopoietin receptor agonist indicated: for the treatment of thrombocytopenia in adult and pediatric patients1 year and older with persistent or chronic immune thrombocytopenia(ITP) who have had an insufficient response to corticosteroids,immunoglobulins, or splenectomy. PROMACTA should be used only inpatients with ITP whose degree of thrombocytopenia and clinicalcondition increase the risk for bleeding. (1.1) for the treatment of thrombocytopenia in patients with chronic hepatitisC to allow the initiation and maintenance of interferon-based therapy.PROMACTA should be used only in patients with chronic hepatitis Cwhose degree of thrombocytopenia prevents the initiation of interferonbased therapy or limits the ability to maintain interferon-based therapy.(1.2) in combination with standard immunosuppressive therapy for the firstline treatment of adult and pediatric patients 2 years and older withsevere aplastic anemia. (1.3) for the treatment of patients with severe aplastic anemia who have had aninsufficient response to immunosuppressive therapy. (1.3)Limitations of Use: PROMACTA is not indicated for the treatment of patients withmyelodysplastic syndrome (MDS). (1.4) Safety and efficacy have not been established in combination withdirect-acting antiviral agents used without interferon for treatment ofchronic hepatitis C infection. (1.4)---------------------------DOSAGE AND ADMINISTRATION------------------ Take PROMACTA without a meal or with a meal low in calcium( 50 mg). Take PROMACTA at least 2 hours before or 4 hours after anymedications or products containing polyvalent cations, such as antacids,calcium-rich foods, and mineral supplements. (2.4, 7.1, 12.3) Persistent or chronic ITP: Initiate PROMACTA at 50 mg once daily formost adult and pediatric patients 6 years and older, and at 25 mg once dailyfor pediatric patients aged 1 to 5 years. Dose reductions are needed forpatients with hepatic impairment and some patients of Asian ancestry.Adjust to maintain platelet count greater than or equal to 50 x 109/L. Do notexceed 75 mg per day. (2.1, 8.6, 8.7) Chronic Hepatitis C-associated Thrombocytopenia: InitiatePROMACTA at 25 mg once daily for all patients. Adjust to achieve targetplatelet count required to initiate antiviral therapy. Do not exceed a dailydose of 100 mg. (2.2)First-line Severe Aplastic Anemia: Initiate PROMACTA once daily at 2.5mg/kg (in pediatric patients aged 2 to 5 years old), 75 mg (pediatric patientsaged 6 to 11 years old), or 150 mg for patients aged 12 years and olderconcurrently with standard immunosuppressive therapy. Reduce initial dosein patients of Asian ancestry. Modify dosage for toxicity or elevated plateletcounts. (2.3, 8.7)Refractory Severe Aplastic Anemia: Initiate PROMACTA at 50 mg oncedaily. Reduce initial dose in patients with hepatic impairment or patients ofAsian ancestry. Adjust to maintain platelet count greater than 50 x 109/L. Donot exceed 150 mg per day. (2.3, 8.6, 8.7)--------------------------DOSAGE FORMS AND STRENGTHS---------------- Tablets: 12.5 mg, 25 mg, 50 mg, and 75 mg (3) For oral suspension: 12.5 mg and 25 mg IONS--------------------------None. (4)-------------------------WARNINGS AND PRECAUTIONS--------------------- Hepatotoxicity: Monitor liver function before and during therapy. (5.2) Increased Risk of Death and Progression of Myelodysplastic Syndromesto Acute Myeloid Leukemia. (5.3) Thrombotic/Thromboembolic Complications: Portal vein thrombosis hasbeen reported in patients with chronic liver disease receiving PROMACTA.Monitor platelet counts regularly. (5.4)---------------------------------ADVERSE REACTIONS---------------------------Across all indications, the most common adverse reactions ( 20% in anyindication) were: anemia, nausea, pyrexia, alanine aminotransferaseincreased, cough, fatigue, headache, and diarrhea. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact NovartisPharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA1088 or E IN SPECIFIC POPULATIONS------------------- Lactation: Advise women not to breastfeed during treatment. (8.2)See 17 for PATIENT COUNSELING INFORMATION and MedicationGuide.Revised: 2/2021
FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: RISK FOR HEPATIC DECOMPENSATION INPATIENTS WITH CHRONIC HEPATITIS C andRISK OF HEPATOTOXICITY1 INDICATIONS AND USAGE1.1 Treatment of Thrombocytopenia in Patients WithPersistent or Chronic Immune Thrombocytopenia1.2 Treatment of Thrombocytopenia in Patients WithHepatitis C Infection1.3 Treatment of Severe Aplastic Anemia1.4 Limitations of Use2 DOSAGE AND ADMINISTRATION2.1 Persistent or Chronic Immune Thrombocytopenia2.2 Chronic Hepatitis C-associated Thrombocytopenia2.3 Severe Aplastic Anemia2.4 Administration3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Hepatic Decompensation in Patients With ChronicHepatitis C5.2 Hepatotoxicity5.3 Increased Risk of Death and Progression ofMyelodysplastic Syndromes to Acute Myeloid Leukemia5.4 Thrombotic/Thromboembolic Complications5.5 Cataracts6 ADVERSE REACTIONS6.1 Clinical Trials Experience6.2 Postmarketing Experience7 DRUG INTERACTIONS7.1 Polyvalent Cations (Chelation)8101112131416177.2 Transporters7.3 Protease Inhibitors7.4 Peginterferon Alfa-2a/b TherapyUSE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Lactation8.3 Females and Males of Reproductive Potential8.4 Pediatric Use8.5 Geriatric Use8.6 Hepatic Impairment8.7 EthnicityOVERDOSAGEDESCRIPTIONCLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 PharmacokineticsNONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility13.2 Animal Pharmacology and/or ToxicologyCLINICAL STUDIES14.1 Persistent or Chronic ITP14.2 Chronic Hepatitis C-associated Thrombocytopenia14.3 Severe Aplastic AnemiaHOW SUPPLIED/STORAGE AND HANDLING16.1 Tablets16.2 For Oral SuspensionPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information arenot listed.
FULL PRESCRIBING INFORMATIONWARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONICHEPATITIS C and RISK OF HEPATOTOXICITYIn patients with chronic hepatitis C, PROMACTA in combination with interferon and ribavirin mayincrease the risk of hepatic decompensation [see Warnings and Precautions (5.1)].PROMACTA may increase the risk of severe and potentially life-threatening hepatotoxicity. Monitorhepatic function and discontinue dosing as recommended [see Warnings and Precautions (5.2)].1INDICATIONS AND USAGE1.1Treatment of Thrombocytopenia in Patients With Persistent or Chronic ImmuneThrombocytopeniaPROMACTA is indicated for the treatment of thrombocytopenia in adult and pediatric patients 1 year and olderwith persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response tocorticosteroids, immunoglobulins, or splenectomy. PROMACTA should be used only in patients with ITPwhose degree of thrombocytopenia and clinical condition increase the risk for bleeding.1.2Treatment of Thrombocytopenia in Patients With Hepatitis C InfectionPROMACTA is indicated for the treatment of thrombocytopenia in patients with chronic hepatitis C to allowthe initiation and maintenance of interferon-based therapy. PROMACTA should be used only in patients withchronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy orlimits the ability to maintain interferon-based therapy.1.3Treatment of Severe Aplastic Anemia PROMACTA is indicated in combination with standard immunosuppressive therapy (IST) for the first-linetreatment of adult and pediatric patients 2 years and older with severe aplastic anemia. PROMACTA is indicated for the treatment of patients with severe aplastic anemia who have had aninsufficient response to immunosuppressive therapy.1.4 Limitations of UsePROMACTA is not indicated for the treatment of patients with myelodysplastic syndromes (MDS) [seeWarnings and Precautions (5.3)].Safety and efficacy have not been established in combination with direct-acting antiviral agents usedwithout interferon for treatment of chronic hepatitis C infection.2DOSAGE AND ADMINISTRATION2.1Persistent or Chronic Immune ThrombocytopeniaUse the lowest dose of PROMACTA to achieve and maintain a platelet count greater than or equal to 50 x 109/Las necessary to reduce the risk for bleeding. Dose adjustments are based upon the platelet count response. Donot use PROMACTA to normalize platelet counts [see Warnings and Precautions (5.4)]. In clinical trials,platelet counts generally increased within 1 to 2 weeks after starting PROMACTA and decreased within 1 to2 weeks after discontinuing PROMACTA [see Clinical Studies (14.1)].Initial Dose Regimen: Adult and Pediatric Patients 6 Years and Older with ITP: Initiate PROMACTA at a doseof 50 mg once daily, except in patients who are of Asian ancestry (such as Chinese, Japanese, Taiwanese,Korean, or Thai) or who have mild to severe hepatic impairment (Child-Pugh Class A, B, C).For patients of Asian ancestry with ITP, initiate PROMACTA at a reduced dose of 25 mg once daily [see Usein Specific Populations (8.7), Clinical Pharmacology (12.3)].
For patients with ITP and mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), initiatePROMACTA at a reduced dose of 25 mg once daily [see Use in Specific Populations (8.6), ClinicalPharmacology (12.3)].For patients of Asian ancestry with ITP and hepatic impairment (Child-Pugh Class A, B, C), consider initiatingPROMACTA at a reduced dose of 12.5 mg once daily [see Clinical Pharmacology (12.3)].Pediatric Patients with ITP Aged 1 to 5 Years: Initiate PROMACTA at a dose of 25 mg once daily [see Use inSpecific Populations (8.7), Clinical Pharmacology (12.3)].Monitoring and Dose Adjustment: After initiating PROMACTA, adjust the dose to achieve and maintain aplatelet count greater than or equal to 50 x 109/L as necessary to reduce the risk for bleeding. Do not exceed adose of 75 mg daily. Monitor clinical hematology and liver tests regularly throughout therapy withPROMACTA and modify the dosage regimen of PROMACTA based on platelet counts as outlined in Table 1.During therapy with PROMACTA, assess complete blood counts (CBCs) with differentials, including plateletcounts, weekly until a stable platelet count has been achieved. Obtain CBCs with differentials, including plateletcounts, monthly thereafter.When switching between the oral suspension and tablet, assess platelet counts weekly for 2 weeks, and thenfollow standard monthly monitoring.Table 1. Dose Adjustments of PROMACTA in Patients With Persistent or Chronic ImmuneThrombocytopeniaPlatelet Count ResultDose Adjustment or Response 50 x 109/L following at least Increase daily dose by 25 mg to a maximum of 75 mg/day.2 weeks of PROMACTAFor patients taking 12.5 mg once daily, increase the dose to25 mg daily before increasing the dose amount by 25 mg. 200 x 109/L to 400 x109/L at any timeDecrease the daily dose by 25 mg. Wait 2 weeks to assessthe effects of this and any subsequent dose adjustments.For patients taking 25 mg once daily, decrease the dose to12.5 mg once daily. 400 x 109/LStop PROMACTA; increase the frequency of plateletmonitoring to twice weekly.Once the platelet count is 150 x 109/L, reinitiate therapyat a daily dose reduced by 25 mg.For patients taking 25 mg once daily, reinitiate therapy at adaily dose of 12.5 mg. 400 x 109/L after 2 weeks oftherapy at lowest dose ofPROMACTADiscontinue PROMACTA.In patients with ITP and hepatic impairment (Child-Pugh Class A, B, C), after initiating PROMACTA or afterany subsequent dosing increase, wait 3 weeks before increasing the dose.Modify the dosage regimen of concomitant ITP medications, as medically appropriate, to avoid excessiveincreases in platelet counts during therapy with PROMACTA. Do not administer more than one dose ofPROMACTA within any 24-hour period.Discontinuation: Discontinue PROMACTA if the platelet count does not increase to a level sufficient to avoidclinically important bleeding after 4 weeks of therapy with PROMACTA at the maximum daily dose of 75 mg.
Excessive platelet count responses, as outlined in Table 1, or important liver test abnormalities also necessitatediscontinuation of PROMACTA [see Warnings and Precautions (5.2)]. Obtain CBCs with differentials,including platelet counts, weekly for at least 4 weeks following discontinuation of PROMACTA.2.2Chronic Hepatitis C-associated ThrombocytopeniaUse the lowest dose of PROMACTA to achieve and maintain a platelet count necessary to initiate and maintainantiviral therapy with pegylated interferon and ribavirin. Dose adjustments are based upon the platelet countresponse. Do not use PROMACTA to normalize platelet counts [see Warnings and Precautions (5.4)]. Inclinical trials, platelet counts generally began to rise within the first week of treatment with PROMACTA [seeClinical Studies (14.2)].Initial Dose Regimen: Initiate PROMACTA at a dose of 25 mg once daily.Monitoring and Dose Adjustment: Adjust the dose of PROMACTA in 25-mg increments every 2 weeks asnecessary to achieve the target platelet count required to initiate antiviral therapy. Monitor platelet counts everyweek prior to starting antiviral therapy.During antiviral therapy, adjust the dose of PROMACTA to avoid dose reductions of peginterferon. MonitorCBCs with differentials, including platelet counts, weekly during antiviral therapy until a stable platelet count isachieved. Monitor platelet counts monthly thereafter. Do not exceed a dose of 100 mg daily. Monitor clinicalhematology and liver tests regularly throughout therapy with PROMACTA.For specific dosage instructions for peginterferon or ribavirin, refer to their respective prescribing information.Table 2. Dose Adjustments of PROMACTA in Adults With Thrombocytopenia Due to ChronicHepatitis CPlatelet Count ResultDose Adjustment or Response9 50 x 10 /L following at least Increase daily dose by 25 mg to a maximum of 100 mg/day.2 weeks of PROMACTA 200 x 109/L to 400 xDecrease the daily dose by 25 mg.109/L at any timeWait 2 weeks to assess the effects of this and any subsequent 400 x109/Ldose adjustments.Stop PROMACTA; increase the frequency of plateletmonitoring to twice weekly.Once the platelet count is 150 x 109/L, reinitiate therapy at adaily dose reduced by 25 mg. 400 x 109/L after 2 weeks oftherapy at lowest dose ofPROMACTAFor patients taking 25 mg once daily, reinitiate therapy at adaily dose of 12.5 mg.Discontinue PROMACTA.Discontinuation: The prescribing information for pegylated interferon and ribavirin include recommendationsfor antiviral treatment discontinuation for treatment futility. Refer to pegylated interferon and ribavirinprescribing information for discontinuation recommendations for antiviral treatment futility.PROMACTA should be discontinued when antiviral therapy is discontinued. Excessive platelet countresponses, as outlined in Table 2, or important liver test abnormalities also necessitate discontinuation ofPROMACTA [see Warnings and Precautions (5.2)].2.3Severe Aplastic AnemiaFirst-Line Severe Aplastic AnemiaInitiate PROMACTA concurrently with standard immunosuppressive therapy [see Clinical Studies (14.3)].
Initial Dose Regimen:The recommended initial dose regimen is listed in Table 3. Do not exceed the initial dose of PROMACTA.Table 3. Recommended Initial PROMACTA Dose Regimen in the First-Line Treatment of SevereAplastic AnemiaAgeDose RegimenPatients 12 years and older150 mg once daily for 6 monthsPediatric patients 6 to 11 years75 mg once daily for 6 monthsPediatric patients 2 to 5 years2.5 mg/kg once daily for 6 monthsFor patients with severe aplastic anemia of Asian ancestry (such as Chinese, Japanese, Taiwanese, Korean, orThai) or those with mild, moderate, or severe hepatic impairment (Child-Pugh Class A, B, C), decrease theinitial PROMACTA dose by 50% as listed in Table 4 [see Use in Specific Populations (8.6, 8.7), ClinicalPharmacology (12.3)].If baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST)levels are 6 x upper limit of normal (ULN), do not initiate PROMACTA until transaminase levels are 5 xULN. Determine the initial dose for these patients based on Table 3 or Table 4.Table 4. Recommended Initial PROMACTA Dose Regimen for Patients of Asian Ancestry or Those WithMild, Moderate, or Severe Hepatic Impairment (Child-Pugh Class A, B, C) in the First-Line Treatmentof Severe Aplastic AnemiaAgeDose RegimenPatients 12 years and older75 mg once daily for 6 monthsPediatric patients 6 to 11 years37.5 mg once daily for 6 monthsPediatric patients 2 to 5 years1.25 mg/kg once daily for 6 monthsMonitoring and Dose Adjustment for PROMACTA: Perform clinical hematology and liver tests regularlythroughout therapy with PROMACTA [see Warnings and Precautions (5.2)].Modify the dosage regimen of PROMACTA based on platelet counts as outlined in Table 5.Table 5. Dose Adjustments of PROMACTA for Elevated Platelet Counts in the First-Line Treatment ofSevere Aplastic AnemiaPlatelet Count ResultDose Adjustment or Response 200 x 109/L to 400 x 109/L Decrease the daily dose by 25 mg every 2 weeks to lowestdose that maintains platelet count 50 x 109/L. 400 x 109/LIn pediatric patients under 12 years of age, decrease the doseby 12.5 mg.Discontinue PROMACTA for one week. Once the plateletcount is 200 x 109/L, reinitiate PROMACTA at a daily dosereduced by 25 mg (or 12.5 mg in pediatric patients under 12years of age).Table 6 summarizes the recommendations for dose interruption, reduction, or discontinuation of PROMACTAin the management of elevated liver transaminase levels and thromboembolic events.
Table 6. Recommended Dose Modifications for PROMACTA for ALT or AST Elevations andThromboembolic EventsEventRecommendationALT or AST ElevationsIncrease in ALT or AST 6 x ULNDiscontinue PROMACTA. Once ALT or AST is 5 x ULN,reinitiate PROMACTA at the same dose.Increase in ALT or AST 6 x ULN after reinitiatingPROMACTADiscontinue PROMACTA and monitor ALT or AST at leastevery 3 to 4 days. Once ALT or AST is 5 x ULN, reinitiatePROMACTA at a daily dose reduced by 25 mg compared tothe previous dose.If ALT or AST returns to 6 x ULN on the reduced doseReduce the daily dose of PROMACTA by 25 mg until ALT orAST is 5 x ULN.Thromboembolic events (e.g.,deep vein thrombosis,pulmonary embolus, stroke,myocardial infarction)In pediatric patients under 12 years of age, reduce the dailydose by at least 15% to the nearest dose that can beadministered.Discontinue PROMACTA but remain on horse antithymocyteglobulin (h-ATG) and cyclosporine.Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.The total duration of PROMACTA treatment is 6 months.Refractory Severe Aplastic AnemiaUse the lowest dose of PROMACTA to achieve and maintain a hematologic response. Dose adjustments ar
Take PROMACTA without a meal or with a meal low in calcium ( 50 mg). Take PROMACTA at least 2 hours before or 4 hours after any medications or products containing polyvalent cations, such as antacids, calcium-rich foods, and mineral supplements. (2.4, 7.1, 12.3) Persistent or chronic ITP: I
