Revolade Dosage/Direction for Use

Dosage: REVOLADE dosing regimens must be individualised based on the patient's platelet counts. In most patients, measurable elevations in platelet counts take 1-2 weeks (see Pharmacology: Pharmacodynamics: Clinical trials under Actions).
Chronic ITP: Use the lowest dose of REVOLADE to achieve and maintain a platelet count ≥ 50 x 10⁹/L as necessary to reduce the risk for bleeding. Dose adjustments are based upon the platelet count response. Do not use REVOLADE in an attempt to normalise platelet counts. In clinical studies, platelet counts generally increased within 1 to 2 weeks after starting REVOLADE and decreased within 1 to 2 weeks after discontinuation.
Initial Dose Regimen: Adults and Paediatric Patients Aged 6 to 17 years: The recommended starting dose of REVOLADE is 50 mg once daily.
For adult and paediatric patients aged 6-17 years of East-/Southeast-Asian ancestry, REVOLADE should be initiated at a reduced dose of 25 mg once daily (see Pharmacology: Pharmacokinetics: Special Patient Populations under Actions).
Paediatric Patients Aged 1 to 5 years: The recommended starting dose of REVOLADE is 25 mg once daily. A lower starting dose (12.5 mg) followed by up-titration can be administered on a case-per-case basis after assessing the risk/benefit.
Monitoring and dose adjustment: Adults and Paediatric Patients Aged 1 to 17 years: After initiating REVOLADE, adjust the dose to achieve and maintain a platelet count ≥ 50 x 10⁹/L as necessary to reduce the risk for bleeding (see Table 10). Do not exceed a dose of 75 mg daily. Monitor clinical haematology and liver function tests regularly throughout therapy with REVOLADE and the dose of REVOLADE modified based on platelet counts as outlined in Table 10. During therapy with REVOLADE, full blood counts (FBCs), including platelet count and peripheral blood smears, should be assessed weekly until a stable platelet count (≥ 50 x 10⁹/L for at least 4 weeks) has been achieved. FBCs including platelet count and peripheral blood smears should be obtained monthly thereafter.
The lowest effective dosing regimen to maintain platelet counts should be used as clinically indicated.
The standard dose adjustment, either decrease or increase, would be 25 mg once daily. However, in a few patients a combination of different tablet strengths on different days or less frequent dosing may be required.
After any REVOLADE dose adjustment, platelet counts should be monitored at least weekly for 2 to 3 weeks. Wait for at least 2 weeks to see the effect of any dose adjustment on the patient's platelet response prior to considering another dose adjustment. In patients with liver cirrhosis (i.e. hepatic impairment), wait 3 weeks before increasing the dose (see Special Populations (all indications) as follows, and Precautions). (See Table 10.)

Click on icon to see table/diagram/image

Discontinuation: Adults and Paediatric Patients Aged 1 to 17 years: Treatment with REVOLADE should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after four weeks of REVOLADE therapy at 75 mg once daily.
Chronic hepatitis C associated thrombocytopenia: When REVOLADE is given in combination with antiviral therapies reference should be made to the full product information of the respective coadministered medicinal products for comprehensive details of administration.
Use the lowest dose of REVOLADE to achieve and maintain a platelet count necessary to initiate and optimise antiviral therapy. Dose adjustments are based upon the platelet count response. Do not use REVOLADE in an attempt to normalize platelet counts. In clinical studies, platelet counts generally increased within 1 week of starting REVOLADE.
Initial Dose Regimen: Adults: Initiate REVOLADE at a dose of 25 mg once daily. No dose adjustment is required in chronic HCV patients of East-/Southeast-Asian ancestry.
Monitoring and dose adjustment: Adults: Adjust the dose of REVOLADE in 25 mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy (see Table 11). Monitor platelet counts every week prior to starting antiviral therapy.
During antiviral therapy adjust the dose of REVOLADE as necessary to avoid dose reduction of peginterferon. Monitor platelet counts weekly during antiviral therapy until a stable platelet count is achieved. FBCs, 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 information. (See Table 11.)

Click on icon to see table/diagram/image

Discontinuation: Adults: 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 therapy, REVOLADE therapy should be discontinued.
REVOLADE treatment should be terminated when antiviral therapy is discontinued. Excessive platelet count responses, as outlined in Table 11 or important liver test abnormalities may also necessitate discontinuation of REVOLADE (see Precautions).
Children: The safety and efficacy of REVOLADE in children with chronic HCV have not been established.
First-line severe aplastic anaemia: REVOLADE should be initiated concurrently with standard immunosuppressive therapy (see Table 12).
The initial dose of REVOLADE should not be exceeded.
Initial dose regimen: Adult and adolescent patients aged 12 to 17 years: The recommended initial dose of REVOLADE is 150 mg once daily for 6 months.
For adult and adolescent SAA patients of East-/Southeast-Asian ancestry, REVOLADE should be initiated at a dose of 75 mg once daily for 6 months.
Paediatric patients aged 6 to 11 years: The recommended initial dose of REVOLADE is 75 mg once daily for 6 months.
For paediatric SAA patients of East-/Southeast-Asian ancestry aged 6 to 11 years, REVOLADE should be initiated at a dose of 37.5 mg once daily for 6 months.
Paediatric patients aged 2 to 5 years: The recommended initial dose of REVOLADE is 2.5 mg/kg once daily for 6 months.
For paediatric SAA patients of East-/Southeast-Asian ancestry aged 2 to 5 years, REVOLADE should be initiated at a dose of 1.25 mg/kg once daily for 6 months. (See Table 12.)

Click on icon to see table/diagram/image

Monitoring and dose adjustment for eltrombopag: Clinical haematology and liver tests should be performed regularly throughout therapy with REVOLADE.
The dosage regimen of REVOLADE should be modified based on platelet counts as outlined in Table 13.
Table 14 summarizes the recommendations for dose interruption, reduction, or discontinuation of REVOLADE in the management of liver function abnormalities and thrombosis/embolism events. (See Tables 13 and 14.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Discontinuation: The total duration of REVOLADE treatment is 6 months.
Excessive platelet count responses (as outlined in Table 13) or certain adverse events (as outlined in Table 14) also necessitate discontinuation of REVOLADE.
Refractory Severe Aplastic Anaemia: Initial Dose Regimen: Adults: Initiate REVOLADE at a dose of 50 mg once daily. For patients of East-/Southeast-Asian ancestry, REVOLADE should be initiated at a dose of 25 mg once daily (see Pharmacology: Pharmacokinetics under Actions and Special Populations (all indications) as follows).
Monitoring and dose adjustment: Adults: Haematological response requires dose titration, generally up to 150 mg, and may take up to 16 weeks after starting REVOLADE (see Pharmacology: Pharmacodynamics: Clinical trials under Actions). Adjust the dose of REVOLADE in 50 mg increments every 2 weeks as necessary to achieve the target platelet count ≥ 50 x 10⁹/L. Do not exceed a dose of 150 mg daily. Monitor clinical haematology and liver tests regularly throughout therapy with REVOLADE and modify the dosage regimen of REVOLADE based on platelet counts as outlined in Table 15. (See Table 15.)

Click on icon to see table/diagram/image

Tapering for tri-lineage (white blood cells, red blood cells, and platelets) responders: Once platelet count > 50 x 10⁹/L, haemoglobin > 100 g/L in the absence of red blood cell (RBC) transfusion, and absolute neutrophil (ANC) > 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 discontinue REVOLADE and monitor blood counts. If platelet counts drop to < 30 x 10⁹/L, haemoglobin to < 90 g/L or ANC < 0.5 x 10⁹/L, REVOLADE may be reinitiated at the previous dose.
Discontinuation: Adults: If no haematological response has occurred after 16 weeks of therapy with REVOLADE, discontinue therapy. Consider REVOLADE discontinuation if new cytogenetic abnormalities are observed (see Adverse Reactions). Excessive platelet count responses (as outlined in Table 15) or important liver test abnormalities also necessitate discontinuation of REVOLADE (see Precautions).
Children: The safety and efficacy of REVOLADE in children with SAA have not been established.
Special Populations (all indications): Elderly: There are limited data on the use of REVOLADE in patients aged 65 years and older. In the clinical studies of REVOLADE, overall no clinically significant differences in efficacy and safety of REVOLADE were observed between patients aged 65 years and older compared to younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out (see Pharmacology: Pharmacokinetics: Special Patient Populations under Actions).
Paediatric patients: The safety and efficacy of REVOLADE have not been established in paediatric patients with ITP younger than 1 year of age, chronic HCV, refractory SAA, and definitive immunosuppressive therapy-naïve SAA patients younger than 2 years of age (see Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical trials under Actions).
Hepatic Impairment: ITP patients with liver cirrhosis (hepatic impairment, Child-Pugh score ≥ 5) should use REVOLADE with caution and close monitoring (see Precautions and also Pharmacology: Pharmacokinetics: Special Patient Populations under Actions). If the use of REVOLADE is deemed necessary for ITP patients with hepatic impairment the starting dose must be 25 mg once daily. After initiating the dose of REVOLADE in patients with hepatic impairment wait 3 weeks before increasing the dose.
Chronic HCV patients with hepatic impairment and severe aplastic anaemia patients with hepatic impairment should initiate REVOLADE at a dose of 25 mg once daily (see Pharmacology: Pharmacokinetics: Special Patient Populations under Actions).
REVOLADE should not be used in patients with hepatic impairment (Child-Pugh score ≥ 5) unless the expected benefit outweighs the identified risk of portal venous thrombosis (see Precautions).
The risk of thromboembolic events (TEEs) has been found to be increased in patients with chronic liver disease treated with 75 mg REVOLADE once daily for two weeks in preparation for invasive procedures (see Precautions).
In a clinical study in definitive immunosuppressive therapy-naïve severe aplastic anaemia, patients with baseline AST/ALT >5 x ULN were ineligible to participate. The initial dose of REVOLADE in patients with hepatic impairment in the first-line setting should be determined as necessary based on clinical judgement, tolerability, and close monitoring of liver function.
Renal Impairment: No dose adjustment is necessary in patients with renal impairment. Patients with impaired renal function should use REVOLADE with caution and close monitoring; for example, by testing serum creatinine and/or performing urine analysis (see Pharmacology: Pharmacokinetics: Special Patient Populations under Actions).
East-/Southeast-Asian patients: For adult and pediatric patients of East-/Southeast-Asian ancestry, REVOLADE should be initiated at a dose of 25 mg once daily for the treatment of ITP, HCV-associated thrombocytopenia, and refractory SAA. For the treatment of patients with first-line SAA refer to Initial Dose Regimen as previously mentioned.
Administration: Swallow REVOLADE with a glass of water, at least two hours before or four hours after any products such as antacids, dairy products, or mineral supplements containing polyvalent cations (e.g. aluminium, calcium (see paragraph as follows), iron, magnesium, selenium, and/or zinc) (see Pharmacology: Pharmacokinetics: Absorption under Actions, and Interactions).
REVOLADE may be taken with food containing little (< 50 mg) or preferably no calcium (see Interactions, and Pharmacology: Pharmacokinetics under Actions).