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Revolade is a brand name for Eltrombopag. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Revolade is indicated for the treatment of adult patients with primary immune thrombocytopenia (ITP) who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) (see sections 4.2 and 5.1). Revolade is indicated for the treatment of paediatric patients aged 1 year and above with primary immune…
Verbatim from this product's EMA label. Tap a section to expand.
Eltrombopag treatment should be initiated by and remain under the supervision of a physician who is experienced in the treatment of haematological diseases or the management of chronic hepatitis C and its complications. Posology Eltrombopag dosing requirements must be individualised based on the patient’s platelet counts.
The objective of treatment with eltrombopag should not be to normalise platelet counts. 2). When switching between the tablet and the powder for oral suspension formulations, platelet counts should be monitored weekly for 2 weeks. Immune (primary) thrombocytopenia The lowest dose of eltrombopag to achieve and maintain a platelet count ≥50 000/μl should be used.
Dose adjustments are based upon the platelet count response. Eltrombopag must not be used to normalise platelet counts. In clinical studies, platelet counts generally increased within 1 to 2 weeks after starting eltrombopag and decreased within 1 to 2 weeks after discontinuation.
Adults and paediatric population aged 6 to 17 years The recommended starting dose of eltrombopag is 50 mg once daily. 2). Paediatric population aged 1 to 5 years The recommended starting dose of eltrombopag is 25 mg once daily. Monitoring and dose adjustment After initiating eltrombopag, the dose must be adjusted to achieve and maintain a platelet count ≥50 000/μl as necessary to reduce the risk for bleeding.
A daily dose of 75 mg must not be exceeded. 4 Clinical haematology and liver tests should be monitored regularly throughout therapy with eltrombopag and the dose regimen of eltrombopag modified based on platelet counts as outlined in Table 1.
During therapy with eltrombopag full blood counts (FBCs), including platelet count and peripheral blood smears, should be assessed weekly until a stable platelet count (≥50 000/μl for at least 4 weeks) has been achieved. FBCs including platelet counts and peripheral blood smears should be obtained monthly thereafter.
Table 1 Dose adjustments of eltrombopag in ITP patients Platelet count Dose adjustment or response <50 000/μl following at least 2 weeks of therapy Increase daily dose by 25 mg to a maximum of 75 mg/day*. 50 000/μl to 150 000/μl Use lowest dose of eltrombopag and/or concomitant ITP treatment to maintain platelet counts that avoid or reduce bleeding.
>150 000/μl to 250 000/μl Decrease the daily dose by 25 mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments♦. >250 000/μl Stop eltrombopag; increase the frequency of platelet monitoring to twice weekly.
1). Patients received study medication for up to 8 years (in EXTEND). The most important serious adverse reactions were hepatotoxicity and thrombotic/thromboembolic events. The most common adverse reactions occurring in at least 10% of patients included nausea, diarrhoea, increased alanine aminotransferase and back pain.
1). PETIT2 (TRA115450) was a two-part, double- blind and open-label, randomised, placebo-controlled study. Patients were randomised 2:1 and received Revolade (n=63) or placebo (n=29) for up to 13 weeks in the randomised period of the study.
PETIT (TRA108062) was a three-part, staggered-cohort, open-label and double-blind, randomised, placebo-controlled study. Patients were randomised 2:1 and received Revolade (n=44) or placebo (n=21), for up to 7 weeks. The profile of adverse reactions was comparable to that seen in adults with some additional adverse reactions, marked ♦ in the table below.
The most common adverse reactions in paediatric ITP patients 1 year and older (≥3% and greater than placebo) were upper respiratory tract infection, nasopharyngitis, cough, pyrexia, abdominal pain, oropharyngeal pain, toothache and rhinorrhoea.
Thrombocytopenia with HCV infection in adult patients ENABLE 1 (TPL103922 n=716, 715 treated with eltrombopag) and ENABLE 2 (TPL108390 n=805) were randomised, double-blind, placebo-controlled, multicentre studies to assess the efficacy and safety of Revolade in thrombocytopenic patients with HCV infection who were otherwise eligible to initiate antiviral therapy.
In the HCV studies the safety population consisted of all randomised patients who received double-blind study medicinal product during Part 2 of ENABLE 1 (Revolade treatment n=450, placebo treatment n=232) and ENABLE 2 (Revolade treatment n=506, placebo treatment n=252).
Patients are analysed according to the treatment received (total safety double-blind population, Revolade n=955 and placebo n=484). The most important serious adverse reactions identified were hepatotoxicity and thrombotic/thromboembolic events.
There is an increased risk for adverse reactions, including potentially fatal hepatic decompensation and thromboembolic events, in thrombocytopenic HCV patients with advanced chronic liver disease, as defined by low albumin levels ≤35 g/l or model for end stage liver disease (MELD) score ≥10, when treated with eltrombopag in combination with interferon-based therapy.
In addition, the benefits of treatment in terms of the proportion achieving sustained virological response (SVR) compared with placebo were modest in these patients (especially for those with baseline albumin ≤35 g/l) compared with the group overall.
Treatment with eltrombopag in these patients should be initiated only by physicians experienced in the management of advanced HCV, and only when the risks of thrombocytopenia or withholding antiviral therapy necessitate intervention.
If treatment is considered clinically indicated, close monitoring of these patients is required. Combination with direct-acting antiviral agents Safety and efficacy have not been established in combination with direct-acting antiviral agents approved for treatment of chronic hepatitis C infection.
8). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin should be measured prior to initiation of eltrombopag, every 2 weeks during the dose adjustment phase and monthly following establishment of a stable dose.
Eltrombopag inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinaemia. If bilirubin is elevated fractionation should be performed. Abnormal serum liver tests should be evaluated with repeat testing within 3 to 5 days.
If the abnormalities are confirmed, serum liver tests should be monitored until the abnormalities resolve, stabilise, or return to baseline levels. Eltrombopag should be discontinued if ALT levels increase (3 times the upper limit of normal [x ULN] in patients with normal liver function, or ≥3 x baseline or >5 x ULN, whichever is the lower, in patients with pre-treatment elevations in transaminases) and are: • progressive, or • persistent for ≥4 weeks, or • accompanied by increased direct bilirubin, or • accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Once the platelet count is ≤ 100 000/μl, reinitiate therapy at a daily dose reduced by 25 mg. * For patients taking 25 mg eltrombopag once every other day, increase dose to 25 mg once daily. 5 mg once daily or alternatively a dose of 25 mg once every other day.
Eltrombopag can be administered in addition to other ITP medicinal products. The dose regimen of concomitant ITP medicinal products should be modified, as medically appropriate, to avoid excessive increases in platelet counts during therapy with eltrombopag.
It is necessary to 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. The standard eltrombopag dose adjustment, either decrease or increase, would be 25 mg once daily.
Discontinuation Treatment with eltrombopag should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks of eltrombopag therapy at 75 mg once daily. Patients should be clinically evaluated periodically and continuation of treatment should be decided on an individual basis by the treating physician.
In non-splenectomised patients this should include evaluation relative to splenectomy. 4). Chronic hepatitis C (HCV) associated thrombocytopenia When eltrombopag is given in combination with antivirals reference should be made to the full summary of product characteristics of the respective coadministered medicinal products for comprehensive details of relevant safety information or contraindications.
5 In clinical studies, platelet counts generally began to increase within 1 week of starting eltrombopag. The aim of treatment with eltrombopag should be to achieve the minimum level of platelet counts needed to initiate antiviral therapy, in adherence to clinical practice recommendations.
During antiviral therapy, the aim of treatment should be to keep platelet counts at a level that prevents the risk of bleeding complications, normally around 50 000-75 000/μl. Platelet counts >75 000/μl should be avoided. The lowest dose of eltrombopag needed to achieve the targets should be used.
Dose adjustments are based upon the platelet count response. Initial dose regimen Eltrombopag should be initiated at a dose of 25 mg once daily. 2). Monitoring and dose adjustment The dose of eltrombopag should be adjusted in 25 mg increments every 2 weeks as necessary to achieve the target platelet count required to initiate antiviral therapy.
Platelet counts should be monitored every week prior to starting antiviral therapy. On initiation of antiviral therapy the platelet count may fall, so immediate eltrombopag dose adjustments should be avoided (see Table 2). During antiviral therapy, the dose of eltrombopag should be adjusted as necessary to avoid dose reductions of peginterferon due to decreasing platelet […]
The most common adverse reactions occurring in at least 10% of patients included headache, anaemia, decreased appetite, cough, nausea, diarrhoea, hyperbilirubinaemia, alopecia, pruritus, myalgia, pyrexia, fatigue, influenza-like illness, asthenia, chills and oedema.
1). The most common adverse reactions occurring in at least 10% of patients included headache, dizziness, cough, oropharyngeal pain, rhinorrhoea, nausea, diarrhoea, abdominal pain, transaminases increased, arthralgia, pain in extremity, muscle spasms, fatigue and pyrexia.
1 for study details). 0%) patients, respectively. Overall, the frequency, type and severity of adverse reactions observed for eltrombopag in paediatric patients with SAA were consistent with those observed in adult patients with SAA.
List of adverse reactions The adverse reactions in the adult ITP studies (N=763), paediatric ITP studies (N=171), the HCV studies (N=1 520), the adult SAA study (N=43), the paediatric SAA study (N=51) and post-marketing reports are listed below by MedDRA system organ class and by frequency (Tables 4, 5 and 6).
Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. The corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); not known (cannot be estimated from the available data).
Table 4 Adverse reactions in the ITP study population System organ class Frequency Adverse reaction Infections and infestations Very common Nasopharyngitis♦, upper respiratory tract infection♦ Common Pharyngitis, influenza, oral herpes, pneumonia, sinusitis, tonsillitis, respiratory tract infection, gingivitis Uncommon Skin infection Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uncommon Rectosigmoid cancer Blood and lymphatic system disorders Common Anaemia, eosinophilia, leukocytosis, thrombocytopenia, haemoglobin decreased, white blood cell count decreased Uncommon Anisocytosis, haemolytic anaemia, myelocytosis, band neutrophil count increased, myelocyte present, platelet count increased, haemoglobin increased Immune system disorders Uncommon Hypersensitivity Metabolism and nutrition disorders Common Hypokalaemia, decreased appetite, blood uric acid increased Uncommon Anorexia, gout, hypocalcaemia Psychiatric disorders Common Sleep disorder, depression Uncommon Apathy, mood altered, tearfulness 17 Nervous system disorders Common […]
Caution is required when administering eltrombopag to patients with hepatic disease. In ITP and SAA patients a lower starting dose of eltrombopag should be used. 2). 9 Hepatic decompensation (use with interferon) Hepatic decompensation in patients with chronic hepatitis C: Monitoring is required in patients with low albumin levels (≤35 g/l) or with MELD score ≥10 at baseline.
Chronic HCV patients with liver cirrhosis may be at risk of hepatic decompensation when receiving alfa interferon therapy. In two controlled clinical studies in thrombocytopenic patients with HCV, hepatic decompensation (ascites, hepatic encephalopathy, variceal haemorrhage, spontaneous bacterial peritonitis) occurred more frequently in the eltrombopag arm (11%) than in the placebo arm (6%).
In patients with low albumin levels (≤35 g/l) or with a MELD score ≥10 at baseline, there was a 3-fold greater risk of hepatic decompensation and an increase in the risk of a fatal adverse event compared to those with less advanced liver disease.
In addition, the benefits of treatment in terms of the proportion achieving SVR compared with placebo were modest in these patients (especially for those with baseline albumin ≤35 g/l) compared with the group overall. Eltrombopag should only be administered to such patients after careful consideration of the expected benefits in comparison with the risks.
Patients with these characteristics should be closely monitored for signs and symptoms of hepatic decompensation. The respective interferon summary of product characteristics should be referenced for discontinuation criteria. Eltrombopag should be terminated if antiviral therapy is discontinued for hepatic decompensation.
Thrombotic/thromboembolic complications In controlled studies in thrombocytopenic patients with HCV receiving interferon-based therapy (n=1 439), 38 out of 955 patients (4%) treated with eltrombopag and 6 out of 484 patients (1%) in the placebo group experienced TEEs.
Reported thrombotic/thromboembolic complications included both venous and arterial events. The majority of TEEs were non-serious and resolved by the end of the study. Portal vein thrombosis was the most common TEE in both treatment groups (2% in patients treated with eltrombopag versus <1% for placebo).
No specific temporal relationship between start of treatment and event of TEE were observed. Patients with low albumin levels (≤35 g/l) or MELD ≥10 had a 2-fold greater risk of TEEs than those with higher albumin levels; those aged ≥60 years had a 2- fold greater risk of TEEs compared to younger patients.
Eltrombopag should only be administered to such patients after careful consideration of the expected benefits in comparison with the risks. Patients should be closely monitored for signs and symptoms of TEE. The risk of TEEs has been found to be increased in patients with chronic liver disease (CLD) treated with 75 mg eltrombopag once daily for 2 weeks in preparation for invasive procedures.
Six of 143 (4%) adult patients with CLD receiving eltrombopag experienced TEEs (all of the portal venous system) and two of 145 (1%) patients in the placebo group experienced TEEs (one in the portal venous system and one myocardial infarction).
Five of the 6 patients treated with eltrombopag experienced the thrombotic complication at a platelet count >200 000/μl and within 30 days of the last dose of eltrombopag. Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease in […]