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REVOLADE is a brand name for Eltrombopag, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations REVOLADE is only available as tablets and cannot be used in patients who are unable to swallow REVOLADE tablets whole. Chronic Immune Thrombocytopenia (ITP) REVOLADE (eltrombopag) treatment should be initiated and maintained by a physician who is experienced in the treatment of haematological diseases, who understands the benefits and risks associated with the treatment of ITP, and who is experienced in counselling patients for whom REVOLADE is indicated.
Prior to prescribing REVOLADE, physicians should: Ensure the eligibility of patients to meet the above criteria, Counsel each patient on the risks and benefits of REVOLADE, and Ensure patients are able to swallow the REVOLADE tablets whole (see Administration below).
REVOLADE dosing regimens must be individualized based on th e patient’s platelet counts. The objective of treatment with REVOLADE should not be to normalize platelet counts but to maintain platelet counts above the level for hemorrhagic risk (> 50 x 109/L), and generally below 150 – 200 x 109/L.
Use the lowest effective dosing regimen to maintain platelet counts, as clinically indicated. In most patients, measurable elevations in platelet counts take 1-2 weeks to occur (see 14 CLINICAL TRIALS). Chronic Hepatitis C-related Thrombocytopenia REVOLADE is given in combination with pegylated interferon and ribavirin.
Reference should be Serious Warnings and Precautions REVOLADE should be used with caution in chronic hepatitis C patients with cirrhosis as it may increase the risk of hepatic decompensation and death when administered with pegylated interferon and ribavirin.
Patients with low albumin levels (< 35 g/L) or Model for End-Stage Liver Disease (MELD) score ≥ 10 at baseline had a greater risk of hepatic decompensation. Patients with these characteristics should be closely monitored for signs and symptoms of hepatic decompensation (see 7 Hepatic/Biliary/Pancreatic, Hepatic Decompensation - Use with Interferon).
Revolade® Eltrombopag (as eltrombopag olamine) Page 6 of 67 made to the full Product Monographs for each respective co-administered medicinal product for comprehensive details of administration. The directions regarding the dosage, dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications for pegylated interferon and ribavirin should be followed.
REVOLADE should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy and limits the ability to maintain interferon-based therapy. Use the lowest dose of REVOLADE to achieve and maintain a platelet count necessary to initiate and maintain antiviral therapy.
Dose adjustments are based upon the patient’s platelet count response, see Table 2, below. Do not use REVOLADE to normalize platelet counts. In clinical studies, platelet counts generally increased within 1 week of starting REVOLADE.
1 Adverse Reaction Overview In the adult ITP clinical studies, hemorrhage was the most common serious adverse reaction and most hemorrhage reactions followed discontinuation of REVOLADE (eltrombopag). Other serious adverse reactions included liver test abnormalities and thromboembolic complications.
Based on an analysis of adult chronic ITP patients receiving REVOLADE in 3 controlled and 2 uncontrolled clinical studies, the median duration of exposure to REVOLADE was 379 days and patient year’s exposure was 584 in this study population.
Based on a final analysis of adult chronic ITP patients receiving REVOLADE in one uncontrolled extension study, the median daily dose was 51 mg and the median duration of exposure was 865 days. The safety of REVOLADE in pediatric patients (aged 1 to 17 years) with previously treated chronic ITP has been demonstrated in a pooled safety population of 157 patients, 107 treated with REVOLADE and 50 treated with placebo.
The median exposure to REVOLADE in the randomized period was 91 days. The most common adverse reactions observed with REVOLADE (≥ 10% and greater than placebo) were upper respiratory tract infection and nasopharyngitis. 0%, REVOLADE versus placebo, respectively.
In the HCV clinical studies, the safety of REVOLADE in combination with interferon and ribavirin is supported by a clinical database of 1576 eltrombopag-treated adult patients enrolled in two pivotal, placebo-controlled, phase III studies and one supportive phase II study.
06. The most commonly reported adverse events were fatigue, headache, myalgia, fever, and rigors. The Product Monographs for both pegylated interferon and ribavirin should be consulted for relevant safety information. In the SAA pivotal phase II study (n=43), nausea, fatigue, cough, diarrhea, and headache were the most common adverse reactions reported.
). The reoccurrence of thrombocytopenia is possible upon discontinuation of treatment.
Chronic Hepatitis C-related Thrombocytopenia Adults (≥ 18 years of age):
REVOLADE should be initiated at a dose of 25 mg once daily. No dosage adjustment is necessary for HCV patients of East-/Southeast-Asian ancestry or patients with mild hepatic impairment. The dose of REVOLADE should be adjusted in 25 mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy (see Table 2).
Platelet counts should be monitored every week prior to starting antiviral therapy. During antiviral therapy, the dose of REVOLADE should be adjusted as necessary to avoid dose reduction of peginterferon. Platelet counts should be monitored weekly during antiviral therapy until a stable platelet count is achieved.
CBC’s, including platelet counts and peripheral blood smears should be obtained monthly thereafter. Do not exceed a dose of 100 mg REVOLADE once daily. For specific dosage instructions for peginterferon alfa or ribavirin, refer to their respective Product Monographs.
Table 2 Dose adjustments of REVOLADE in HCV patients during antiviral therapy Platelet Count Result Dose Adjustment or Response < 50 x 109/L following at least 2 weeks of therapy Increase daily dose by 25 mg increments every 2 weeks as necessary to a maximum of 100 mg / day.
For patients taking 25 mg once every other day, increase the dose to 25 mg once daily before increasing the dose amount by 25 mg. ≥ 50 x 109/L to ≤ 150 x 109/L Maintain the lowest dose of REVOLADE to achieve these values so as to avoid dose reductions of peginterferon.
> 150 x 109/L to ≤ 200 x 109/L Decrease the daily dose by 25 mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. For patients taking 25 mg REVOLADE once daily, consideration should be given to dosing at 25 mg once every other day.
REVOLADE (eltrombopag) is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) (see 7 Hepatic/Biliary/Pancreatic, Hepatic Impairment and Hepatotoxicity). REVOLADE (eltrombopag) is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container For a complete listing of excipients (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).
In patients with chronic hepatitis C virus (HCV) infection, the Product Monographs for both pegylated interferon and ribavirin should be consulted for relevant contraindications associated with the use of these products. Revolade® Eltrombopag (as eltrombopag olamine) Page 5 of 67
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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The safety and efficacy of REVOLADE have not been established in combination with direct acting antiviral agents used in the treatment of chronic hepatitis C virus infection. Severe Aplastic Anemia (SAA) Use the lowest dose of REVOLADE to achieve and maintain a hematologic response.
Dose adjustments are based upon the platelet count. Do not use REVOLADE to normalize platelet counts (see 7 Hematologic, Thrombotic or thromboembolic complications). 1 Severe Aplastic Anemia). 2 Recommended Dose and Dosage Adjustment Chronic Immune Thrombocytopenia (ITP) Initial Dose Regimen Adults and Pediatric Patients Aged 6 years and above: The recommended starting dose of REVOLADE is 50 mg once daily.
For ITP patients of East- /Southeast-Asian ancestry aged 6 and above, initiate REVOLADE at a reduced dose of 25 mg once daily (see 4 DOSAGE AND ADMINISTRATION).
Pediatric Patients Aged 1 to < 6 years:
The recommended starting dose of REVOLADE is 25 mg once daily. g. 50 x 109/L), the dose may be increased to a maximum of 75 mg once daily (see Table 1). Revolade® Eltrombopag (as eltrombopag olamine) Page 7 of 67 A dose reduction should be considered with platelet counts increasing to over 150 x 109/L.
At platelet counts over 200 x 109/L dose reduction is recommended (see Table 1). REVOLADE should be interrupted if platelet counts increase to > 300 x 109/L. Once the platelet count is < 150 x 109/L; reinitiate therapy at a reduced dose.
If platelet counts remain at > 300 x 109/L after 2 weeks of therapy of the lowest dose of REVOLADE, discontinue treatment (see Table 1). Table 1 Dose Adjustments of REVOLADE in ITP patients Platelet Count Result Dose Adjustment or Response < 50 x 109/L following at least 2 weeks of REVOLADE Increase daily dose by 25 mg to a maximum of 75 mg/day For patients taking 25 mg once every other day, increase dose to 25 mg once daily.
≥ 50 x 109/L to ≤ 200 x 109/L Use lowest dose of REVOLADE and/or concomitant ITP treatment to maintain platelet counts that avoid or reduce bleeding. > 200 x 109/L to ≤ 300 x 109/L at any time Decrease the daily dose by 25 mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments For patients taking 25 mg once daily, consideration should be given to dosing at 25 mg once every other day.
> 300 x 109/L Stop REVOLADE. Increase the frequency of platelet monitoring to twice weekly. Once the platelet count is < 150 x 109/L, reinitiate therapy at a daily dose reduced by 25 mg. For patients taking 25 mg once daily, consideration should be given to reinitiating therapy at 25 mg once every other day.
> 300 x 109/L after 2 weeks of therapy at lowest dose of REVOLADE Discontinue REVOLADE The standard dose adjustment, […]
The most common serious adverse events reported were febrile neutropenia, sepsis and viral infection. 2 Clinical Trial Adverse Reactions Clinical trials were conducted under very specific conditions. The adverse reaction rates observed Revolade® Eltrombopag (as eltrombopag olamine) Page 21 of 67 in the clinical trials therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying and approximating rates of adverse drug reactions in the real world use. Adult Chronic Immune Thrombocytopenia (ITP) The safety of REVOLADE has been demonstrated in two randomised, double -blind, placebo controlled studies in 211 adults with previously treated chronic ITP (see 14 CLINICAL TRIALS).
Most adverse reactions associated with REVOLADE were mild to moderate in severity, early in onset and rarely treatment limiting. The most common adver se events were nausea, vomiting, diarrhea and headache. The drug-related adverse events occurring in ≥ 1% of adult patients, and which were more common in the treatment group as compared to placebo in the Phase III, double- blind, placebo-controlled 6 week study, TRA100773B, and 6 month study, RAISE (TRA102537), are presented in Table 5 and Table 6, respectively.
The safety of REVOLADE over long-term dosing was evaluated in one single arm, open-label, extension study, EXTEND (TRA105325), in 302 adult patients with previously treated chronic ITP who were previously enrolled in an eltrombopag study.
Overall, the safety data from this study reflect the known safety profile of REVOLADE. Drug-related adverse events occurring in ≥ 3% of patients are presented in Table 7. Table 5 Drug-Related Adverse Events ≥ 1% in Adult ITP Patients over 6 weeks (Study TRA100773B) Body System/Adverse Event Treatment Group, n (%) REVOLADE N=76 Placebo N=38 Cardiac disorders Sinus tachycardia 1(1) 0 Gastrointestinal Nausea 4(5) 0 Vomiting 2(3) 0 Abdominal distension 1(1) 0 Constipation 1(1) 0 Diarrhea 1(1) 0 Hemorrhoids 1(1) 0 Hepatobiliary disorders Hepatic function abnormal 1(1) 0 General disorders and administration site conditions Fatigue 2(3) 0 Revolade® Eltrombopag (as eltrombopag olamine) Page 22 of 67 Malaise 1(1) 0 Investigations Protein total increased 3(4) 1(3) ALT increased 2(3) 0 AST increased 2(3) 0 Metabolism and nutrition disorders Hypokalemia 1(1) 0 Musculoskeletal and connective tissue disorders Myalgia 3(4) 0 Arthralgia 1(1) 0 Bone pain 1(1) 0 Nervous system disorders Headache 4(5) 1(3) Psychiatric disorders Sleep disorder 1(1) 0 Skin and subcutaneous tissue disorders Alopecia 1(1) 0 Night sweats 1(1) 0 Table 6 Drug-Related Adverse Events ≥ 1% in Adult ITP Patients over 6 months (RAISE) Body System/Adverse Event Treatment Group, n (%) REVOLADE N=135 Placebo N=61 Eye disorders Dry eye 2(1) 0 Gastrointestinal Nausea 6(4) 0 Constipation 3(2) 1(2) Diarrhea 4(3) 0 Dry mouth 3(2) 0 Vomiting 2(1) 0 General Disorders and Administration Site Conditions Revolade® Eltrombopag (as eltrombopag olamine) Page 23 of 67 Body System/Adverse Event Treatment Group, n (%) REVOLADE N=135 Placebo N=61 Feeling hot 2(1) 0 Hepatobiliary disorders Hepatic function abnormal 2(1) 0 Investigations ALT increased 6(4) 2(3) Hemoglobin increased 2(1) 0 Transaminases increased 2(1) 0 Musculoskeletal and connective tissue disorders Arthralgia 2(1) 0 Nervous system disorder Headache 15(11) 5(8) Paraesthesia 3(2) 0 Skin and subcutaneous tissue disorders Hyperhidrosis 3(2) 0 Rash 2(1) 0 EXTEND (TRA105325) Table 7 Drug- Related Adverse Events ≥ 3% in Adult Chronic ITP Patients in EXTEND (Safety Population) Preferred Term Eltrombopag N=302 Any AE; n (%) 133 (44) Headache 30 (10) Alanine aminotransferase increased 16 (5) Aspartate aminotransferase increased 15 (5) Cataract 15 (5) Fatigue 14 (5) Blood bilirubin increased 12 (4) Nausea 11 (4) Revolade® […]
Revolade® Eltrombopag (as eltrombopag olamine) Page 9 of 67 Platelet Count Result Dose Adjustment or Response > 200 x 109/L Stop REVOLADE; increase the frequency of platelet monitoring to twice weekly. Once the platelet count is < 150 x 109/L, reinitiate therapy at a lower daily dose.
For patients taking 25 mg REVOLADE once daily, consideration should be given to reinitiating therapy at 25 mg once every other day > 200 x 109/L after 2 weeks of therapy at lowest dose of REVOLADE Discontinue REVOLADE Discontinuation When REVOLADE is given in combination with antiviral therapies reference should be made to the full Product Monograph of the respective co-administered medicinal products for comprehensive details of administration.
The directions regarding the dose, dose adjustment guidelines in the event of toxicity and other relevant safety information or contraindications for the respective antiviral medicinal products should be followed. In patients with HCV genotype 1/4/6, independent of the decision to continue interferon therapy, discontinuation of REVOLADE therapy should be considered in patients who do not achieve virological response at week 12.
If HCV-RNA remains detectable after 24 weeks of treatment, REVOLADE therapy should be discontinued. REVOLADE treatment should be terminated when antiviral therap y is discontinued. Excessive platelet count responses, as outlined in Table 2 or important liver test abnormalities may also necessitate discontinuation of REVOLADE (see 7 WARNINGS AND PRECAUTIONS).
Severe Aplastic Anemia (SAA) Adults (≥ 18 years of age):
REVOLADE should be initiated at a dose of 50 mg once daily. For SAA patients of East- /Southeast-Asian ancestry or those with mild or moderate hepatic impairment (Child-Pugh Class A, B), REVOLADE should be initiated at a reduced dose of 25 mg once daily (See 4 DOSAGE AND ADMINISTRATION).
The dose of REVOLADE should be initiated in 50 mg increments every 2 weeks as necessary to achieve the target platelet count ≥ 50 x 109/L. For patients with mild or moderate hepatic impairment or patients of East-/Southeast-Asian ancestry, increase the dose initially by 25 mg to achieve a 50 mg daily dose before considering further dose increases.
Do not exceed a dose of 150 mg daily. Clinical hematology and liver tests should be monitored regularly throughout therapy with REVOLADE and the dosage regimen of REVOLADE should be modified b ased on platelet counts as outlined in Table 3.
Revolade® Eltrombopag (as eltrombopag olamine) Page 10 of 67 Table 3 Dose adjustments of REVOLADE in SAA patients Platelet Count Result Dose Adjustment or Response < 50 x 109/L following at least 2 weeks of REVOLADE Increase daily dose by 50 mg every two weeks as necessary to a maximum of 150 mg/day.
For patients taking 25 mg once daily, increase the dose to 50 mg daily before increasing the dose amount by 50 mg. ≥ 50 x 109/L to ≤ 200 x 109/L Maintain the lowest dose of REVOLADE to achieve these values. e. in the East-/Southeast-Asian ancestry or in patients with liver disease).
Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. > 300 x 109/L Stop REVOLADE for at least one week. Once the platelet count is < 150 x 109/L, reinitiate therapy at a dose reduced by 50 mg. > 300 x 109/L after 2 weeks of therapy at lowest dose of REVOLADE Discontinue REVOLADE.
Tapering for Tri-lineage (white blood cells, red blood cells, and platelets) Responders: Once platelet count is > 50 x 109/L, hemoglobin is > 100 g/L in the absence of red blood cell (RBC) transfusions, and absolute neutrophil count (ANC) is > 1 x 109/L for more than 8 weeks, the dose of REVOLADE should be reduced by up to 50%.
If counts stay stable after 8 weeks at the reduced dose, then REVOLADE should be discontinued and blood counts monitored as clinically indicated. 5 x 109/L, REVOLADE […]