REVOLADE
Contraindications
Hypersensitivity to eltrombopag or to any of the excipients.
Special warnings and precautions for use
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 ≤35g/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.
Risk of hepatotoxicity
Eltrombopag administration can cause abnormal liver function and severe hepatotoxicity, which might be life-threatening.
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.
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. Close monitoring is required when administering to patients with hepatic impairment.
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 cirrhosis may be at risk of hepatic decompensation when receiving alfa interferon therapy. In 2 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 thromboembolic events (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 2 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 preparation for invasive procedures.
In eltrombopag clinical studies in ITP thromboembolic events were observed at low and normal platelet counts. Caution should be used when administering eltrombopag to patients with known risk factors for thromboembolism including but not limited to inherited (e.g. Factor V Leiden) or acquired risk factors (e.g. ATIII deficiency, antiphospholipid syndrome), advanced age, patients with prolonged periods of immobilisation, malignancies, contraceptives and hormone replacement therapy, surgery/trauma, obesity and smoking. Platelet counts should be closely monitored and consideration given to reducing the dose or discontinuing eltrombopag treatment if the platelet count exceeds the target levels. The risk-benefit balance should be considered in patients at risk of TEEs of any aetiology.
No case of TEE was identified from a clinical study in refractory SAA, however the risk of these events cannot be excluded in this patient population due to the limited number of exposed patients. As the highest authorised dose is indicated for patients with SAA (150 mg/day) and due to the nature of the reaction, TEEs might be expected in this patient population.
Eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score ≥5) unless the expected benefit outweighs the identified risk of portal venous thrombosis. When treatment is considered appropriate, caution is required when administering eltrombopag to patients with hepatic impairment.
Bleeding following discontinuation of eltrombopag
Thrombocytopenia is likely to reoccur in ITP patients upon discontinuation of treatment with eltrombopag. Following discontinuation of eltrombopag, platelet counts return to baseline levels within 2 weeks in the majority of patients, which increases the bleeding risk and in some cases may lead to bleeding. This risk is increased if eltrombopag treatment is discontinued in the presence of anticoagulants or anti-platelet agents. It is recommended that, if treatment with eltrombopag is discontinued, ITP treatment be restarted according to current treatment guidelines. Additional medical management may include cessation of anticoagulant and/or anti-platelet therapy, reversal of anticoagulation, or platelet support. Platelet counts must be monitored weekly for 4 weeks following discontinuation of eltrombopag.
In HCV clinical studies, a higher incidence of gastrointestinal bleeding, including serious and fatal cases, was reported following discontinuation of peginterferon, ribavirin, and eltrombopag. Following discontinuation of therapy, patients should be monitored for any signs or symptoms of gastrointestinal bleeding.
Bone marrow reticulin formation and risk of bone marrow fibrosis
Eltrombopag may increase the risk for development or progression of reticulin fibres within the bone marrow. The relevance of this finding, as with other thrombopoietin receptor (TPO-R) agonists, has not been established yet.
Prior to initiation of eltrombopag, the peripheral blood smear should be examined closely to establish a baseline level of cellular morphologic abnormalities. Following identification of a stable dose of eltrombopag, full blood count (FBC) with white blood cell count (WBC) differential should be performed monthly. If immature or dysplastic cells are observed, peripheral blood smears should be examined for new or worsening morphological abnormalities (e.g. teardrop and nucleated red blood cells, immature white blood cells) or cytopenia(s). If the patient develops new or worsening morphological abnormalities or cytopenia(s), treatment with eltrombopag should be discontinued and a bone marrow biopsy considered, including staining for fibrosis.
Progression of existing myelodysplastic syndrome (MDS)
There is a theoretical concern that TPO-R agonists may stimulate the progression of existing haematological malignancies such as MDS. TPO-R agonists are growth factors that lead to thrombopoietic progenitor cell expansion, differentiation and platelet production. The TPO-R is predominantly expressed on the surface of cells of the myeloid lineage. For TPO-R agonists there is a concern that they may stimulate the progression of existing haematopoietic malignancies such as MDS.
In clinical studies with a TPO-R agonist in patients with MDS, cases of transient increases in blast cell counts were observed and cases of MDS disease progression to acute myeloid leukaemia (AML) were reported.
The diagnosis of ITP or SAA in adults and elderly patients should be confirmed by the exclusion of other clinical entities presenting with thrombocytopenia, in particular the diagnosis of MDS must be excluded. Consideration should be given to performing a bone marrow aspirate and biopsy over the course of the disease and treatment, particularly in patients over 60 years of age, those with systemic symptoms, or abnormal signs such as increased peripheral blast cells.
The effectiveness and safety of REVOLADE have not been established for the treatment of thrombocytopenia due to MDS. REVOLADE should not be used outside of clinical studies for the treatment of thrombocytopenia due to MDS.
Cytogenetic abnormalities and progression to MDS/AML in patients with SAA
Cytogenetic abnormalities are known to occur in SAA patients. It is not known whether eltrombopag increases the risk of cytogenetic abnormalities in patients with SAA. In the phase II refractory SAA clinical study with eltrombopag with a starting dose of 50 mg/day (escalated every 2 weeks to a maximum of 150 mg/day) (ELT112523), the incidence of new cytogenetic abnormalities was observed in 17.1% of adult patients [7/41 (where 4 of them had changes in chromosome 7)]. The median time on study to a cytogenetic abnormality was 2.9 months.
In the phase II refractory SAA clinical study with eltrombopag at a dose of 150 mg/day (with ethnic or age related modifications as indicated) (ELT116826), the incidence of new cytogenetic abnormalities was observed in 22.6% of adult patients [7/31 (where 3 of them had changes in chromosome 7)]. All 7 patients had normal cytogenetics at baseline. Six patients had cytogenetic abnormality at Month 3 of eltrombopag therapy and one patient had cytogenetic abnormality at Month 6.
In clinical studies with eltrombopag in SAA, 4% of patients (5/133) were diagnosed with MDS. The median time to diagnosis was 3 months from the start of eltrombopag treatment.
For SAA patients refractory to or heavily pretreated with prior immunosuppressive therapy, bone marrow examination with aspirations for cytogenetics is recommended prior to initiation of eltrombopag, at 3 months of treatment and 6 months thereafter. If new cytogenetic abnormalities are detected, it must be evaluated whether continuation of eltrombopag is appropriate.
Ocular changes
Cataracts were observed in toxicology studies of eltrombopag in rodents. In controlled studies in thrombocytopenic patients with HCV receiving interferon therapy (n=1,439), progression of pre-existing baseline cataract(s) or incident cataracts was reported in 8% of the eltrombopag group and 5% of the placebo group. Retinal haemorrhages, mostly Grade 1 or 2, have been reported in HCV patients receiving interferon, ribavirin and eltrombopag (2% of the eltrombopag group and 2% of the placebo group). Haemorrhages occurred on the surface of the retina (preretinal), under the retina (subretinal), or within the retinal tissue. Routine ophthalmologic monitoring of patients is recommended.
QT/QTc prolongation
A QTc study in healthy volunteers dosed 150 mg eltrombopag per day did not show a clinically significant effect on cardiac repolarisation. QTc interval prolongation has been reported in clinical studies of patients with ITP and thrombocytopenic patients with HCV. The clinical significance of these QTc prolongation events is unknown.
Loss of response to eltrombopag
A loss of response or failure to maintain a platelet response with eltrombopag treatment within the recommended dosing range should prompt a search for causative factors, including an increased bone marrow reticulin.
Paediatric population
The above warnings and precautions for ITP also apply to the paediatric population.
Interference with laboratory tests
Eltrombopag is highly coloured and so has the potential to interfere with some laboratory tests. Serum discolouration and interference with total bilirubin and creatinine testing have been reported in patients taking REVOLADE. If the laboratory results and clinical observations are inconsistent, re-testing using another method may help in determining the validity of the result.
Interaction with other medicinal products and other forms of interaction
Effects of eltrombopag on other medicinal products
HMG CoA reductase inhibitors
Administration of eltrombopag 75 mg once daily for 5 days with a single 10 mg dose of the OATP1B1 and BCRP substrate rosuvastatin to 39 healthy adult subjects increased plasma rosuvastatin Cmax 103% (90% confidence interval [CI]: 82%, 126%) and AUC0-∞ 55% (90% CI: 42%, 69%). Interactions are also expected with other HMG-CoA reductase inhibitors, including atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin. When co-administered with eltrombopag, a reduced dose of statins should be considered and careful monitoring for statin adverse reactions should be undertaken.
OATP1B1 and BCRP substrates
Concomitant administration of eltrombopag and OATP1B1 (e.g. methotrexate) and BCRP (e.g. topotecan and methotrexate) substrates should be undertaken with caution.
Cytochrome P450 substrates
In studies utilising human liver microsomes, eltrombopag (up to 100 µM) showed no in vitro inhibition of the CYP450 enzymes 1A2, 2A6, 2C19, 2D6, 2E1, 3A4/5, and 4A9/11 and was an inhibitor of CYP2C8 and CYP2C9 as measured using paclitaxel and diclofenac as the probe substrates. Administration of eltrombopag 75 mg once daily for 7 days to 24 healthy male subjects did not inhibit or induce the metabolism of probe substrates for 1A2 (caffeine), 2C19 (omeprazole), 2C9 (flurbiprofen), or 3A4 (midazolam) in humans. No clinically significant interactions are expected when eltrombopag and CYP450 substrates are co-administered.
HCV protease inhibitors
Dose adjustment is not required when eltrombopag is co-administered with either telaprevir or boceprevir. Co-administration of a single dose of eltrombopag 200 mg with telaprevir 750 mg every 8 hours did not alter plasma telaprevir exposure.
Co-administration of a single dose of eltrombopag 200 mg with boceprevir 800 mg every 8 hours did not alter plasma boceprevir AUC(0-𝜏), but increased Cmax by 20%, and decreased Cmin by 32%. The clinical relevance of the decrease in Cmin has not been established: increased clinical and laboratory monitoring for HCV suppression is recommended.
Effects of other medicinal products on eltrombopag
Ciclosporin
A decrease in eltrombopag exposure was observed with co-administration of 200 mg and 600 mg ciclosporin (a BCRP inhibitor). The co-administration of 200 mg ciclosporin decreased the Cmax and the AUCinf of eltrombopag by 25% and 18%, respectively. The co-administration of 600 mg ciclosporin decreased the Cmax and the AUCinf of eltrombopag by 39% and 24%, respectively. Eltrombopag dose adjustment is permitted during the course of the treatment based on the patient’s platelet count. Platelet count should be monitored at least weekly for 2 to 3 weeks when eltrombopag is co-administered with ciclosporin. Eltrombopag dose may need to be increased based on these platelet counts.
Polyvalent cations (chelation)
Eltrombopag chelates with polyvalent cations such as iron, calcium, magnesium, aluminium, selenium and zinc. Administration of a single dose of eltrombopag 75 mg with a polyvalent cation-containing antacid (1524 mg aluminium hydroxide and 1425 mg magnesium carbonate) decreased plasma eltrombopag AUC0-∞ by 70% (90% CI: 64%, 76%) and Cmax by 70% (90% CI: 62%, 76%). Eltrombopag should be taken at least two hours before or four hours after any products such as antacids, dairy products or mineral supplements containing polyvalent cations to avoid significant reduction in eltrombopag absorption due to chelation.
Lopinavir/ritonavir
Co-administration of eltrombopag with lopinavir/ritonavir may cause a decrease in the concentration of eltrombopag. A study in 40 healthy volunteers showed that the co-administration of a single 100 mg dose of eltrombopag with repeat dose lopinavir/ritonavir 400/100 mg twice daily resulted in a reduction in eltrombopag plasma AUCinf by 17% (90% CI: 6.6%, 26.6%). Therefore, caution should be used when co-administration of eltrombopag with lopinavir/ritonavir takes place. Platelet count should be closely monitored in order to ensure appropriate medical management of the dose of eltrombopag when lopinavir/ritonavir therapy is initiated or discontinued.
CYP1A2 and CYP2C8 inhibitors and inducers
Eltrombopag is metabolised through multiple pathways including CYP1A2, CYP2C8, UGT1A1, and UGT1A3. Medicinal products that inhibit or induce a single enzyme are unlikely to significantly affect plasma eltrombopag concentrations, whereas medicinal products that inhibit or induce multiple enzymes have the potential to increase (e.g. fluvoxamine) or decrease (e.g. rifampicin) eltrombopag concentrations.
HCV protease inhibitors
Results of a drug-drug pharmacokinetic (PK) interaction study show that co-administration of repeat doses of boceprevir 800 mg every 8 hours or telaprevir 750 mg every 8 hours with a single dose of eltrombopag 200 mg did not alter plasma eltrombopag exposure to a clinically significant extent.
Medicinal products for treatment of ITP
Medicinal products used in the treatment of ITP in combination with eltrombopag in clinical studies included corticosteroids, danazol, and/or azathioprine, intravenous immunoglobulin (IVIG), and anti-D immunoglobulin. Platelet counts should be monitored when combining eltrombopag with other medicinal products for the treatment of ITP in order to avoid platelet counts outside of the recommended range.
Food interaction
The administration of eltrombopag tablet or powder for oral suspension formulations with a high-calcium meal (e.g. a meal that included dairy products) significantly reduced plasma eltrombopag AUC0-∞ and Cmax. In contrast, the administration of eltrombopag 2 hours before or 4 hours after a high-calcium meal or with low-calcium food [<50 mg calcium] did not alter plasma eltrombopag exposure to a clinically significant extent.
Administration of a single 50 mg dose of eltrombopag in tablet form with a standard high-calorie, high-fat breakfast that included dairy products reduced plasma eltrombopag mean AUC0-∞ by 59% and mean Cmax by 65%.
Administration of a single 25 mg dose of eltrombopag as powder for oral suspension with a high-calcium, moderate-fat and moderate-calorie meal reduced plasma eltrombopag mean AUC0-∞ by 75% and mean Cmax by 79%. This decrease of exposure was attenuated when a single 25 mg dose of eltrombopag powder for oral suspension was administered 2 hours before a high-calcium meal (mean AUC0-∞ was decreased by 20% and mean Cmax by 14%).
Food low in calcium (<50 mg calcium), including fruit, lean ham, beef and unfortified (no added calcium, magnesium or iron) fruit juice, unfortified soya milk and unfortified grain, did not significantly impact plasma eltrombopag exposure, regardless of calorie and fat content.
Fertility, pregnancy and lactation
Pregnancy
There are no or limited amount of data from the use of eltrombopag in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.
REVOLADE is not recommended during pregnancy.
Women of childbearing potential / Contraception in males and females
REVOLADE is not recommended in women of childbearing potential not using contraception.
Breast-feeding
It is not known whether eltrombopag/metabolites are excreted in human milk. Studies in animals have shown that eltrombopag is likely secreted into milk; therefore a risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to continue/abstain from REVOLADE therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
Fertility was not affected in male or female rats at exposures that were comparable to those in humans. However a risk for humans cannot be ruled out.
Effects on ability to drive and use machines
Eltrombopag has negligible influence on the ability to drive and use machines. The clinical status of the patient and the adverse reaction profile of eltrombopag, including dizziness and lack of alertness, should be borne in mind when considering the patient’s ability to perform tasks that require judgement, motor and cognitive skills.
Undesirable effects
Summary of the safety profile
Immune thrombocytopenia in adult and paediatric patients
The safety of REVOLADE was assessed using the pooled double-blind, placebo-controlled studies TRA100773A and B, TRA102537 (RAISE) and TRA113765, in which 403 patients were exposed to REVOLADE and 179 to placebo, in addition to data from the completed open-label studies TRA108057, TRA105325 (EXTEND) and TRA112940. 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 and increased alanine aminotransferase.
The safety of REVOLADE in paediatric patients (aged 1 to 17 years) with previously treated ITP has been demonstrated in two studies. PETIT2 (TRA115450) was a 2-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 3-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) 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=253). 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. 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.
Severe aplastic anaemia in adult patients
The safety of eltrombopag in severe aplastic anaemia was assessed in a single-arm, open-label study (N=43) in which 11 patients (26%) were treated for >6 months and 7 patients (21%) were treated for >1 year. The most important serious adverse reactions were febrile neutropenia and sepsis/infection. The most common adverse reactions occurring in at least 10% of patients included headache, dizziness, cough, oropharyngeal pain, nausea, diarrhoea, abdominal pain, transaminases increased, arthralgia, pain in extremity, fatigue and pyrexia.
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 SAA studies (N=43) and post-marketing reports are listed below by MedDRA system organ class and by frequency. 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).
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 | |
| Nervous system disorders | Common | Paraesthesia, hypoaesthesia, somnolence, migraine |
| Uncommon | Tremor, balance disorder, dysaesthesia, hemiparesis, migraine with aura, neuropathy peripheral, peripheral sensory neuropathy, speech disorder, toxic neuropathy, vascular headache | |
| Eye disorders | Common | Dry eye, vision blurred, eye pain, visual acuity reduced |
| Uncommon | Lenticular opacities, astigmatism, cataract cortical, lacrimation increased, retinal haemorrhage, retinal pigment epitheliopathy, visual impairment, visual acuity tests abnormal, blepharitis, keratoconjunctivitis sicca | |
| Ear and labyrinth disorders | Common | Ear pain, vertigo |
| Cardiac disorders | Uncommon | Tachycardia, acute myocardial infarction, cardiovascular disorder, cyanosis, sinus tachycardia, electrocardiogram QT prolonged |
| Vascular disorders | Common | Deep vein thrombosis, haematoma, hot flush |
| Uncommon | Embolism, thrombophlebitis superficial, flushing | |
| Respiratory, thoracic and mediastinal disorders | Very common | Cough♦ |
| Common | Oropharyngeal pain, rhinorrhoea♦ | |
| Uncommon | Pulmonary embolism, pulmonary infarction, nasal discomfort, oropharyngeal blistering, sinus disorder, sleep apnoea syndrome | |
| Gastrointestinal disorders | Very common | Nausea, diarrhoea♦ |
| Common | Mouth ulceration, toothache♦, vomiting, abdominal pain*, mouth haemorrhage, flatulence *Very common in paediatric ITP | |
| Uncommon | Dry mouth, glossodynia, abdominal tenderness, faeces discoloured, food poisoning, frequent bowel movements, haematemesis, oral discomfort | |
| Hepatobiliary disorders | Very common | Alanine aminotransferase increased† |
| Common | Aspartate aminotransferase increased†, hyperbilirubinaemia, hepatic function abnormal | |
| Uncommon | Cholestasis, hepatic lesion, hepatitis, drug-induced liver injury | |
| Skin and subcutaneous tissue disorders | Common | Rash, alopecia, hyperhidrosis, pruritus generalised, petechiae |
| Uncommon | Urticaria, dermatosis, cold sweat, erythema, melanosis, pigmentation disorder, skin discolouration, skin exfoliation | |
| Musculoskeletal and connective tissue disorders | Common | Myalgia, muscle spasm, musculoskeletal pain, bone pain, back pain |
| Uncommon | Muscular weakness | |
| Renal and urinary disorders | Common | Proteinuria, blood creatinine increased, thrombotic microangiopathy with renal failure‡ |
| Uncommon | Renal failure, leukocyturia, lupus nephritis, nocturia, blood urea increased, urine protein/creatinine ratio increased | |
| Reproductive system and breast disorders | Common | Menorrhagia |
| General disorders and administration site conditions | Common | Pyrexia*, chest pain, asthenia *Very common in paediatric ITP |
| Uncommon | Feeling hot, vessel puncture site haemorrhage, feeling jittery, inflammation of wound, malaise, sensation of foreign body | |
| Investigations | Common | Blood alkaline phosphatase increased |
| Uncommon | Blood albumin increased, protein total increased, blood albumin decreased, pH urine increased | |
| Injury, poisoning and procedural complications | Uncommon | Sunburn |
Additional adverse reactions observed in paediatric studies (aged 1 to 17 years).
Increase of alanine aminotransferase and aspartate aminotransferase may occur simultaneously, although at a lower frequency.
Grouped term with preferred terms acute kidney injury and renal failure.
HCV study population (in combination with anti-viral interferon and ribavirin therapy)
| System organ class | Frequency | Adverse reaction |
| Infections and infestations | Common | Urinary tract infection, upper respiratory tract infection, bronchitis, nasopharyngitis, influenza, oral herpes |
| Uncommon | Gastroenteritis, pharyngitis | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Common | Hepatic neoplasm malignant |
| Blood and lymphatic system disorders | Very common | Anaemia |
| Common | Lymphopenia | |
| Uncommon | Haemolytic anaemia | |
| Metabolism and nutrition disorders | Very common | Decreased appetite |
| Common | Hyperglycaemia, abnormal loss of weight | |
| Psychiatric disorders | Common | Depression, anxiety, sleep disorder |
| Uncommon | Confusional state, agitation | |
| Nervous system disorders | Very common | Headache |
| Common | Dizziness, disturbance in attention, dysgeusia, hepatic encephalopathy, lethargy, memory impairment, paraesthesia | |
| Eye disorders | Common | Cataract, retinal exudates, dry eye, ocular icterus, retinal haemorrhage |
| Ear and labyrinth disorders | Common | Vertigo |
| Cardiac disorders | Common | Palpitations |
| Respiratory, thoracic and mediastinal disorders | Very common | Cough |
| Common | Dyspnoea, oropharyngeal pain, dyspnoea exertional, productive cough | |
| Gastrointestinal disorders | Very common | Nausea, diarrhoea |
| Common | Vomiting, ascites, abdominal pain, abdominal pain upper, dyspepsia, dry mouth, constipation, abdominal distension, toothache, stomatitis, gastrooesophagal reflux disease, haemorrhoids, abdominal discomfort, varices oesophageal | |
| Uncommon | Oesophageal varices haemorrhage, gastritis, aphthous stomatitis | |
| Hepatobiliary disorders | Common | Hyperbilirubinaemia, jaundice, drug-induced liver injury |
| Uncommon | Portal vein thrombosis, hepatic failure | |
| Skin and subcutaneous tissue disorders | Very common | Pruritus |
| Common | Rash, dry skin, eczema, rash pruritic, erythema, hyperhidrosis, pruritus generalised, alopecia | |
| Uncommon | Skin lesion, skin discolouration, skin hyperpigmentation, night sweats | |
| Musculoskeletal and connective tissue disorder | Very common | Myalgia |
| Common | Arthralgia, muscle spasms, back pain, pain in extremity, musculoskeletal pain, bone pain | |
| Renal and urinary disorders | Uncommon | Thrombotic microangiopathy with acute renal failure†, dysuria |
| General disorders and administration site conditions | Very common | Pyrexia, fatigue, influenza-like illness, asthenia, chills |
| Common | Irritability, pain, malaise, injection site reaction, non-cardiac chest pain, oedema, oedema peripheral | |
| Uncommon | Injection site pruritus, injection site rash, chest discomfort | |
| Investigations | Common | Blood bilirubin increased, weight decreased, white blood cell count decreased, haemoglobin decreased, neutrophil count decreased, international normalised ratio increased, activated partial thromboplastin time prolonged, blood glucose increased, blood albumin decreased |
| Uncommon | Electrocardiogram QT prolonged |
†Grouped term with preferred terms oliguria, renal failure and renal impairment.
SAA study population
| System organ class | Frequency | Adverse reaction |
| Blood and lymphatic system disorders | Common | Neutropenia, splenic infarction |
| Metabolism and nutrition disorders | Common | Iron overload, decreased appetite, hypoglycaemia, increased appetite |
| Psychiatric disorders | Common | Anxiety, depression |
| Nervous system disorders | Very common | Headache, dizziness |
| Common | Syncope | |
| Eye disorders | Common | Dry eye, cataract, ocular icterus, vision blurred, visual impairment, vitreous floaters |
| Respiratory, thoracic and mediastinal disorders | Very common | Cough, oropharyngeal pain, rhinorrhoea |
| Common | Epistaxis | |
| Gastrointestinal disorders | Very common | Diarrhoea, nausea, gingival bleeding, abdominal pain |
| Common | Oral mucosal blistering, oral pain, vomiting, abdominal discomfort, constipation, abdominal distension, dysphagia, faeces discoloured, swollen tongue, gastrointestinal motility disorder, flatulence | |
| Hepatobiliary disorders | Very common | Transaminases increased |
| Common | Blood bilirubin increased (hyperbilirubinemia), jaundice | |
| Not known | Drug-induced liver injury* *Cases of drug-induced liver injury have been reported in patients with ITP and HCV | |
| Skin and subcutaneous disorders | Common | Petechiae, rash, pruritus, urticaria, skin lesion, rash macular |
| Not known | Skin discolouration, skin hyperpigmentation | |
| Musculoskeletal and connective tissue disorders | Very common | Arthralgia, pain in extremity, muscle spasms |
| Common | Back pain, myalgia, bone pain | |
| Renal and urinary disorders | Common | Chromaturia |
| General disorders and administration site conditions | Very common | Fatigue, pyrexia, chills |
| Common | Asthenia, oedema peripheral, malaise | |
| Investigations | Common | Blood creatine phosphokinase increased |
Description of selected adverse reactions
Thrombotic/thromboembolic events (TEEs)
In 3 controlled and 2 uncontrolled clinical studies among adult ITP patients receiving eltrombopag (n=446), 17 patients experienced a total of 19 TEEs, which included (in descending order of occurrence) deep vein thrombosis (n=6), pulmonary embolism (n=6), acute myocardial infarction (n=2), cerebral infarction (n=2), embolism (n=1).
In a placebo-controlled study (n=288, Safety population), following 2 weeks’ treatment in preparation for invasive procedures, 6 of 143 (4%) adult patients with chronic liver disease receiving eltrombopag experienced 7 TEEs of the portal venous system and 2 of 145 (1%) patients in the placebo group experienced 3 TEEs. Five of the 6 patients treated with eltrombopag experienced the TEE at a platelet count >200,000/μl
No specific risk factors were identified in those patients who experienced a TEE with the exception of platelet counts ≥200,000/μl.
In controlled studies in thrombocytopenic patients with HCV (n=1,439), 38 out of 955 patients (4%) treated with eltrombopag experienced a TEE and 6 out of 484 patients (1%) in the placebo group experienced TEEs. Portal vein thrombosis was the most common TEE in both treatment groups (2% in patients treated with eltrombopag versus <1% for placebo). 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.
Hepatic decompensation (use with interferon)
Chronic HCV patients with cirrhosis may be at risk of hepatic decompensation when receiving alfa interferon therapy. In 2 controlled clinical studies in thrombocytopenic patients with HCV, hepatic decompensation (ascites, hepatic encephalopathy, variceal haemorrhage, spontaneous bacterial peritonitis) was reported more frequently in the eltrombopag arm (11%) than in the placebo arm (6%). In patients with low albumin levels (≤35 g/l) or 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. 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.
Hepatotoxicity
In the controlled clinical studies in chronic ITP with eltrombopag, increases in serum ALT, AST and bilirubin were observed.
These findings were mostly mild (Grade 1-2), reversible and not accompanied by clinically significant symptoms that would indicate an impaired liver function. Across the 3 placebo-controlled studies in adults with chronic ITP, 1 patient in the placebo group and 1 patient in the eltrombopag group experienced a Grade 4 liver test abnormality. In two placebo-controlled studies in paediatric patients (aged 1 to 17 years) with chronic ITP, ALT ≥3 x ULN was reported in 4.7% and 0% of the eltrombopag and placebo groups, respectively.
In 2 controlled clinical studies in patients with HCV, ALT or AST ≥3 x ULN was reported in 34% and 38% of the eltrombopag and placebo groups, respectively. Most patients receiving eltrombopag in combination with peginterferon/ribavirin therapy will experience indirect hyperbilirubinaemia. Overall, total bilirubin ≥1.5 x ULN was reported in 76% and 50% of the eltrombopag and placebo groups, respectively.
In the single-arm phase II monotherapy refractory SAA study, concurrent ALT or AST >3 x ULN with total (indirect) bilirubin >1.5 x ULN were reported in 5% of patients. Total bilirubin >1.5 x ULN occurred in 14% of patients.
Thrombocytopenia following discontinuation of treatment
In the 3 controlled clinical ITP studies, transient decreases in platelet counts to levels lower than baseline were observed following discontinuation of treatment in 8% and 8% of the eltrombopag and placebo groups, respectively.
Increased bone marrow reticulin
Across the programme, no patients had evidence of clinically relevant bone marrow abnormalities or clinical findings that would indicate bone marrow dysfunction. In a small number of ITP patients, eltrombopag treatment was discontinued due to bone marrow reticulin.
Cytogenetic abnormalities
In the phase II refractory SAA clinical study with eltrombopag with a starting dose of 50 mg/day (escalated every 2 weeks to a maximum of 150 mg/day) (ELT112523), the incidence of new cytogenetic abnormalities was observed in 17.1% of adult patients [7/41 (where 4 of them had changes in chromosome 7)]. The median time on study to a cytogenetic abnormality was 2.9 months.
In the phase II refractory SAA clinical study with eltrombopag at a dose of 150 mg/day (with ethnic or age related modifications as indicated) (ELT116826), the incidence of new cytogenetic abnormalities was observed in 22.6% of adult patients [7/31 (where 3 of them had changes in chromosome 7)]. All 7 patients had normal cytogenetics at baseline. Six patients had cytogenetic abnormality at Month 3 of eltrombopag therapy and one patient had cytogenetic abnormality at Month 6.
Haematologic malignancies
In the single-arm, open-label study in SAA, three (7%) patients were diagnosed with MDS following treatment with eltrombopag, in the two ongoing studies (ELT116826 and ELT116643), 1/28 (4%) and 1/62 (2%) patient has been diagnosed with MDS or AML in each study.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system (WC500139752.doc)
Overdose
In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications. In case of an overdose, consideration should be given to oral administration of a metal cation-containing preparation, such as calcium, aluminium, or magnesium preparations to chelate eltrombopag and thus limit absorption. Platelet counts should be closely monitored. Treatment with eltrombopag should be reinitiated in accordance with dosing and administration recommendations.
In the clinical studies there was one report of overdose where the patient ingested 5000 mg of eltrombopag. Reported adverse reactions included mild rash, transient bradycardia, ALT and AST elevation, and fatigue. Liver enzymes measured between Days 2 and 18 after ingestion peaked at a 1.6-fold ULN in AST, a 3.9-fold ULN in ALT, and a 2.4-fold ULN in total bilirubin. The platelet counts were 672,000/μl on Day 18 after ingestion and the maximum platelet count was 929,000/μl. All events were resolved without sequelae following treatment.
Because eltrombopag is not significantly renally excreted and is highly bound to plasma proteins, haemodialysis would not be expected to be an effective method to enhance the elimination of eltrombopag.
FAQs
What is eltrombopag olamine used for? ›
A drug used to treat thrombocytopenia (a low blood platelet count) in adults and children with chronic immune thrombocytopenic purpura that did not get better with other treatment. Eltrombopag olamine is also used to treat severe aplastic anemia.
Is eltrombopag a chemotherapy drug? ›Eltrombopag, is US Food and Drug Administration (FDA) approved for treatment of non-chemotherapy related disorders of low platelets like chronic immune thrombocytopenia (ITP).
What are the common side effects of Revolade? ›The most common side effects of Revolade when used to treat adult patients with chronic ITP include headache, anemia, decreased appetite, insomnia, cough, nausea, diarrhea, alopecia, pruritus, myalgia, pyrexia, fatigue, influenza-like illness, asthenia, chills and peripheral edema.
Is eltrombopag toxic to the liver? ›Eltrombopag administration can cause abnormal liver function and severe hepatotoxicity, which might be life-threatening.
How long can you take eltrombopag for? ›Interim results from this study showed that treatment with eltrombopag was safe, well-tolerated, and effective in maintaining platelet counts in the desired range for most of the 299 patients treated for up to 3 years. This final study report describes up to 8 years of continuous treatment with eltrombopag.
How long does it take for Revolade to work? ›In clinical studies, platelet counts generally increased within 1 to 2 weeks after starting eltrombopag and decreased within 1 to 2 weeks after discontinuation. The recommended starting dose of eltrombopag is 50 mg once daily.
What foods to avoid while taking eltrombopag? ›Too much calcium (more than 50 mg) stops PROMACTA from working properly. So you need to be careful to avoid eating calcium-rich foods such as dairy products (yogurt, cheese, milk, ice cream), calcium-fortified foods (some orange juice, dry cereal, and bread), and leafy green vegetables (spinach, collard greens).
How much is eltrombopag cost? ›Pay $ 12,830 chevron_right at Costco with a GoodRx discount. That's 3% off the retail price of $13188. Pay $ 12,213 chevron_right at Rite Aid with a GoodRx discount. That's 7% off the retail price of $13188.
What happens when you stop taking eltrombopag? ›Eltrombopag oral tablet is used for long-term treatment. It comes with serious risks if you don't take it as prescribed. If you stop taking the drug suddenly or don't take it at all: Your platelet counts may decrease. If your platelet level drops dangerously low, it can cause bleeding.
How effective is Revolade? ›Revolade was shown to be more effective than placebo: in the first study, 59% of the patients who took Revolade (43 out of 73) achieved a platelet count of at least 50,000 per microlitre (a platelet level considered adequate to prevent the risk of bleeding complications) after six weeks (the main measure of ...
What are the benefits of Revolade? ›
Revolade is a medicine that is used for the treatment of: • primary immune thrombocytopenia (ITP), a disease in which the patient's immune system destroys platelets (components in the blood that help it to clot). Patients with ITP have low platelet counts in the blood (thrombocytopenia) and are at risk of bleeding.
Is eltrombopag a steroid? ›Conclusion: Eltrombopag is effective as a rapidly acting corticosteroid sparing therapy for patients with ITP associated with SLE.
When is the best time to take Revolade? ›Take REVOLADE at least 2 hours before or at least 4 hours after antacids, dairy products or some mineral supplements such as iron, calcium, magnesium, aluminium, selenium and zinc. One way to avoid issues with these products would be to take them in the morning and REVOLADE in the evening.
When should I stop eltrombopag? ›Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered.
What type of drug is Revolade? ›Eltrombopag belongs to the class of medications called thrombopoietin receptor agonists. It is used to increase the number of platelets in the blood for adults and children with chronic (long-term) immune thrombocytopenia purpura (ITP).
What is the success rate of eltrombopag? ›A pooled analysis of both trials showed that 62% of the patients treated for six weeks with eltrombopag achieved a response compared to 24% of the placebo group. Response was defined as an increase in platelet count of at least 50 × 109/L. Bleeding risk was significantly lower with eltrombopag than with placebo [18].
How long does it take for 50 mg of eltrombopag to increase platelet count? ›Among patients who were receiving the two highest doses of eltrombopag, more than 80% had increased their platelet count by day 15: this increment allowed platelets to approach their normal range, and was seen in 88% and 81% of patients receiving a daily dose of 50 or 75 mg respectively, with the median platelet counts ...
Is Revolade an immunosuppressant? ›Revolade is used in adult patients whose disease is not controlled by immunosuppressive therapy (medicines that lower the body's immune defences) and cannot receive haematopoietic stem cell transplantation (where the patient's bone marrow is replaced by stem cells from a donor to form new bone marrow).
What are the side effects of Revolade 25 mg? ›In some cases, Revolade 25mg Tablet 7's can cause common side effects like nausea, diarrhoea, headache, muscle pain, tiredness, loss of appetite, fever, anaemia (lack of blood cells), cough and tingling numbness. These side effects are not familiar to everyone who take Revolade 25mg Tablet 7's and vary individually.
Is eltrombopag hazardous? ›Ecotoxical effects: · Remark: Very toxic for fish · Additional ecological information: · General notes: Water hazard class 3 (Self-assessment): extremely hazardous for water Do not allow product to reach ground water, water course or sewage system, even in small quantities.
Is Revolade the same as PROMACTA? ›
Eltrombopag, sold under the brand name Promacta among others, is a medication used to treat thrombocytopenia (abnormally low platelet counts) and severe aplastic anemia. Eltrombopag is sold under the brand name Revolade outside the US and is marketed by Novartis.
What vitamins should I avoid with ITP? ›For example, people who are taking blood thinners are advised to avoid vitamin K. Some vitamins and supplements, such as vitamin E and omega-3 fatty acids (fish oil), can make it more difficult for platelets to clot.
Are eggs good for ITP? ›While specific foods might not immediately raise platelet count, nutritious eating can help manage this fatigue. The Association recommends plenty of fruits and vegetables, whole grain bread and other starches, lower-fat dairy, lean meat, fish, eggs, beans, nuts, and seeds.
Can ITP patients drink coffee? ›Although this is something that might warrant further study, most of my ITP patients have reported no increased risk of bleeding (even at very low platelet counts) when they drink coffee.
Does Medicare pay for PROMACTA? ›Do Medicare prescription drug plans cover Promacta? Yes. 100% of Medicare prescription drug plans cover this drug.
How much does Revolade cost? ›| Drug/Comparator | Strength | Price ($) |
|---|---|---|
| Eltrombopag (Revolade)a | 25 mg | 62.50 |
| 50 mg | 125.00 |
Eltrombopag is the generic name for the trade name drug Promacta. In some cases, health care professionals may use the trade name, Promacta, when referring to the generic drug name, eltrombopag.
Should Revolade be taken before or after food? ›Eltrombopag may be taken at any time of the day or night provided patients remember to take eltrombopag at least 2 hours before or 4 hours after certain foods, drinks, and medicines. However, patients may find it easier to remember if they take it at the same time every day.
What class of drug is eltrombopag? ›Eltrombopag is a thrombopoietin receptor agonist used to treat thrombocytopenia or aplastic anemia associated with various etiologies.
Is eltrombopag an immunosuppressant? ›Furthermore, in addition to its direct stimulatory action on hematopoiesis, eltrombopag might contribute to the immunosuppressive effect of ATG plus cyclosporine.
What medication can increase platelets? ›
Medications such as romiplostim (Nplate) and eltrombopag (Promacta) help your bone marrow produce more platelets.
What is long term treatment for ITP? ›Most of ITP patients respond to primary treatment such as glucocorticoids or IVIG, but a significant number of patients eventually require secondary treatment because the maintain of long-term responses are difficult. Such patients may consider medical therapy (TPO-RA, rituximab) or surgical option (splenectomy).
How long does chronic ITP last? ›Chronic ITP lasts 6 months or longer and mostly affects adults. However, some teens and children do get this type of ITP. Chronic ITP affects women two to three times more often than it affects men.
Can eltrombopag cause back pain? ›The most common side effects reported in ITP patients have included nausea, diarrhea, upper respiratory tract infection, vomiting, increased ALT, myalgia, urinary tract infection, oropharyngeal pain, increased AST, pharyngitis, back pain, influenza, paresthesia, and rash.
Does eltrombopag cause anemia? ›The most common side effects of PROMACTA in adults and children include: low red blood cell count (anemia)
What are the ingredients in Revolade? ›Revolade film-coated tablets are round, biconvex, brown, and debossed with 'GS UFU' and '50' on one side. They contain 64 mg of eltrombopag olamine, equivalent to 50 mg of eltrombopag. Revolade tablets contains the active ingredient eltrombopag olamine. Sodium starch glycollate • Titanium dioxide (E171).
Does PROMACTA cause hair loss? ›sleep problems (insomnia), temporary hair loss, or. cold symptoms such as stuffy nose, sneezing, cough, or sore throat.
Is eltrombopag FDA approved? ›Promacta ®/Revolade ® (eltrombopag)
Promacta/Revolade is approved in the US and in the European Union for the treatment of thrombocytopenia in pediatric patients 1 year and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Interactions between your drugs
No interactions were found between Promacta and Tylenol. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.
REVOLADE may be taken with food containing little (< 50 mg) or preferably no calcium (see section 4.5 and section 5.2). 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.
How do I stop Revolade? ›
Don't stop taking Revolade without talking to your doctor. If your doctor advises you to stop treatment, your platelet count will then be checked each week for four weeks. See also 'Bleeding or bruising after you stop treatment' in section 4.
What is the guidance for eltrombopag? ›The dose of eltrombopag should be adjusted in 50 mg increments every 2 weeks as necessary to achieve the target platelet count ≥50,000/µl. For patients taking 25 mg once daily, the dose should be increased to 50 mg daily before increasing the dose amount by 50 mg. A dose of 150 mg daily must not be exceeded.
What is the equivalent of eltrombopag olamine? ›Revolade 12.5 mg film-coated tablets Each film-coated tablet contains eltrombopag olamine equivalent to 12.5 mg eltrombopag.
What is treatment free remission in ITP? ›treatment-free remission with Nplate®. This means their platelet counts reached and stayed above 50,000 so that they were able to stop any ITP treatment for at least 6 months. About half of adults achieved treatment-free remission by about 6 months with Nplate®.
How often is eltrombopag taken? ›Adults and children 6 years of age and older—At first, 50 milligrams (mg) once a day. Some patients may start at a lower dose. Your doctor may adjust your dose as needed. However, the dose is usually not more than 75 mg per day.