Eltrombopag olamine oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing eltrombopag.
Drugs List
Therapeutic Indications
Uses
Acquired severe aplastic anaemia (SAA)- ineligible for stem cell transplant
Idiopathic thrombocytopenic purpura
Thrombocytopenia in patients with chronic hepatitis C
Treatment of idiopathic thrombocytopenic purpura (ITP) in adult patients who are refractory to other treatments.
Treatment of idiopathic thrombocytopenic purpura (ITP) lasting 6 months or longer from diagnosis in paediatric patients aged 1 year and over who are refractory to other treatments.
Treatment of thrombocytopenia in adult patients with chronic hepatitis C virus (HCV) infection, where the degree of thrombocytopenia is the main factor preventing the initiation or limiting the ability to maintain optimal interferon-based therapy.
Treatment of adult patients with acquired severe aplastic anaemia (SAA) who were either refractory to prior immunosuppressive therapy or heavily pretreated, and are unsuitable for haematopoietic stem cell transplantation.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local protocols for the relevant indication should be consulted.
Adults
Idiopathic thrombocytopenic purpura
Initial dose: 50mg eltrombopag once daily.
For patients of East/Southeast Asian ancestry, eltrombopag should be initiated at a reduced dose of 25mg once daily.
The dose should then be adjusted to achieve and maintain a platelet count equal to or greater than 50,000/microlitre as necessary to reduce the risk of bleeding.
Do not exceed a dose of 75mg daily.
Chronic hepatitis C (HCV) associated thrombocytopenia
Initial dose: 25mg eltrombopag once daily.
The dose should then be adjusted to achieve and maintain a platelet count of around 50,000/microlitre to 75,000/microlitre as necessary to reduce the risk of bleeding.
Do not exceed a dose of 100mg daily.
Severe Aplastic Anaemia
Initial dose: 50mg eltrombopag once daily.
For patients of East/Southeast Asian ancestry, eltrombopag should be initiated at a reduced dose of 25mg once daily.
The dose should then be adjusted to achieve and maintain a platelet count equal to or greater than 50,000/microlitre as necessary to reduce the risk of bleeding.
Do not exceed a dose of 150mg daily.
Children
Idiopathic thrombocytopenic purpura
Children aged 6 to 18 years
Initial dose: 50mg eltrombopag once daily.
For patients of East/Southeast Asian ancestry, eltrombopag should be initiated at a reduced dose of 25mg once daily.
The dose should then be adjusted to achieve and maintain a platelet count equal to or greater than 50,000/microlitre as necessary to reduce the risk of bleeding.
Do not exceed a dose of 75mg daily.
Children aged 1 to 5 years
Initial dose: 25mg eltrombopag once daily.
The dose should then be adjusted to achieve and maintain a platelet count equal to or greater than 50,000/microlitre as necessary to reduce the risk of bleeding.
Do not exceed a dose of 75mg daily.
Patients with Hepatic Impairment
Idiopathic thrombocytopenic purpura
Eltrombopag should not be used in patients with hepatic impairment (Child-Pugh score equal to or greater than 5) unless the expected benefits outweigh the identified risk of portal venous thrombosis. If it is deemed necessary, the starting dose should be 25mg once daily. After initiating the dose in patients with hepatic impairment there should be an interval of three weeks before increasing the dose.
Chronic hepatitis C (HCV) associated thrombocytopenia and Severe Aplastic Anaemia
Patients should initiate eltrombopag at a dose of 25mg once daily. After initiating the dose of eltrombopag wait 2 weeks before increasing the dose.
Additional Dosage Information
Dose adjustments based on platelet count:
Idiopathic thrombocytopenic purpura
Platelets less than 50,000/microlitre following at least 2 weeks of therapy
Increase daily dose by 25mg to a maximum of 75mg/day. (For patients taking 25mg eltrombopag once every other day, increase dose to 25mg once daily).
Platelet count between 50,000/microlitre and 150,000/microlitre
Use lowest dose of eltrombopag and/or concomitant ITP treatment to maintain platelet counts that avoid or reduce bleeding.
Platelet count between 150,000/microlitre and 250,000/microlitre
Decrease the daily dose by 25mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. (For patients taking 25mg eltrombopag once daily, consideration should be given to dosing at 12.5mg once daily or alternatively a dose of 25mg once every other day).
Platelet count greater than 250,000/microlitre
Stop eltrombopag; increase the frequency of platelet monitoring to twice weekly. Once platelet count is equal to or less than 100,000/microlitre, reinitiate therapy at a daily dose reduced by 25mg.
It is recommended to wait for at least 2 weeks to see the effect of any dose adjustment on the patient's platelet response. The standard eltrombopag dose adjustment, either decrease or increase, would be 25mg once daily.
Treatment should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after four weeks of eltrombopag therapy at 75mg once daily.
Chronic hepatitis C (HCV) associated thrombocytopenia
Platelets less than 50,000/microlitre following at least 2 weeks of therapy
Increase daily dose by 25mg to a maximum of 100mg/day.
Platelet count between 50,000/microlitre and 100,000/microlitre
Use lowest dose of eltrombopag as necessary to avoid dose reductions of peginterferon.
Platelet count between 100,000/microlitre and 150,000/microlitre
Decrease the daily dose by 25mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments. (On initiation of antiviral therapy the platelet count may fall, so immediate eltrombopag dose reductions should be avoided).
Platelet count greater than 150,000/microlitre
Stop eltrombopag; increase the frequency of platelet monitoring to twice weekly. Once platelet count is equal to or less than 100,000/microlitre, reinitiate therapy at a daily dose reduced by 25mg. (For patients taking 25mg eltrombopag once daily, consideration should be given to reinitiating dosing at 25mg every other day).
If after 2 weeks of therapy at 100mg the required platelet level to initiate antiviral therapy is not achieved, eltrombopag should be discontinued.
Severe Aplastic Anaemia
Platelets less than 50,000/microlitre following at least 2 weeks of therapy
Increase daily dose by 50mg to a maximum of 150mg/day.
For patients taking 25mg once daily, increase the dose to 50mg daily before increasing the dose amount by 50mg.
Platelet count between 50,000/microlitre and 150,000/microlitre
Use lowest dose of eltrombopag to maintain platelet counts.
Platelet count between 150,000/microlitre and 250,000/microlitre
Decrease the daily dose by 50mg. Wait 2 weeks to assess the effects of this and any subsequent dose adjustments.
Platelet count greater than 250,000/microlitre
Stop eltrombopag; for at least one week. Once platelet count is equal to or less than 100,000/microlitre, reinitiate therapy at a daily dose reduced by 50mg.
Patients who achieve tri-lineage response, including transfusion independence, lasting at least 8 weeks: the dose may be reduced by 50%.
If platelet counts remain stable after 8 weeks at the reduced dose, then discontinue eltrombopag and monitor blood counts. If platelet counts drop to less than 30,000/microlitre, haemoglobin to less than 9g/dL or ANC less than 0.5 x 10 to the power of 9/L, eltrombopag may be reinitiated at the previous effective dose.
If no haematological response has occurred after 16 weeks of therapy with eltrombopag, discontinue therapy. If new cytogenic abnormalities are detected, evaluate whether continuation of eltrombopag is appropriate.
Contraindications
Children under 1 year
Breastfeeding
Cytogenetic abnormalities of chromosome 7 - if treating aplastic anaemia
Pregnancy
Precautions and Warnings
Children aged 1 to 18 years
East/Southeast Asian ancestry
Females of childbearing potential
Patients over 75 years
Predisposition to venous thromboembolism
Decompensated hepatic disease with chronic hepatitis
Hepatic impairment
Myelodysplastic syndrome
Renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Consider reduced dose in patients of East/Southeast Asian ancestry
Treatment to be administered under the supervision of a specialist
Perform baseline LFTs, repeat every 2 weeks if adjusting dose, then monthly
Perform peripheral blood smear prior to and during treatment
Check ocular lens frequently - risk of cataract formation
Investigate patients developing a sudden lack of response to treatment
Monitor blood values and liver function regularly
Monitor for gastrointestinal bleeding following discontinuation of therapy
Monitor for signs and symptoms of thrombosis
Monitor full blood count regularly
Monitor platelet counts for 4 weeks following discontinuation
Monitor platelets
May affect results of some laboratory tests
Discontinue if new or worsening cytopenias develop
Discontinue if new or worsening morphological cell abnormalities develop
Discontinue if transaminases reach > 3 times upper limit of normal
Reduce dose or discontinue if platelets exceed target levels
Bioavailability differs with preparations;caution on changing formulations
Not licensed for all indications in all age groups
Avoid dairy/antacids/mineral supplements 4 hours before/2 hours after dose
Female: Ensure adequate contraception during treatment
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 less than or equal to 35g/litre or model for end stage liver disease (MELD) score greater than or equal to 10, when treated with eltrombopag in combination with interferon-based therapy. Treatment with eltrombopag 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. Close monitoring of these patients is required. Eltrombopag should be terminated if antiviral therapy is discontinued for hepatic decompensation.
Eltrombopag should be discontinued if ALT levels increase to greater than or equal to 3 times the ULN in patients with normal liver function; or greater than or equal to 3 times baseline (or more than 5 times ULN, whichever is lower) in patients with pre-treatment elevations in transaminases and are progressive or persistent for 4 weeks or more or accompanied by increased direct bilirubin or accompanied by the clinical symptoms of liver injury or evidence of hepatic decompensation.
The safety and effectiveness of eltrombopag has not been established for use in other thrombocytopenic conditions including chemotherapy-induced thrombocytopenia and myelodysplastic syndromes.
Complete blood counts including platelet count and peripheral blood smears, should be assessed weekly until a stable platelet count, equal to or greater than 50,000/microlitre for at least 4 weeks, has been achieved. Complete blood counts and peripheral blood smears should be obtained monthly thereafter.
Eltrombopag should be discontinued if antiviral therapy is discontinued for hepatic decompensation.
Platelet counts should be monitored weekly for 2 weeks when switching from between the tablet and oral suspension formulations.
Pregnancy and Lactation
Pregnancy
Eltrombopag is contraindicated during pregnancy.
The manufacturer does not recommend using eltrombopag during pregnancy. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Eltrombopag is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues eltrombopag or discontinues breastfeeding. Animal data reports that eltrombopag is likely to be secreted into milk however the presence in human breast milk is unknown.
Side Effects
Alopecia
Anaemia
Anisocytosis
Anorexia
Anxiety
Apathy
Arthralgia
Asthenia
Cardiovascular disturbances
Cataracts
Changes in hepatic function
Cholestasis
Cough
Cyanosis
Decrease in haemoglobin
Deep vein thrombosis (DVT)
Depression
Disturbances of appetite
Dizziness
Dry eyes
Dysaesthesia
Dysgeusia
Embolism
Eosinophilia
Epistaxis
Eye disorder
Fatigue
Flushing
Gastro-intestinal symptoms
Gingival bleeding
Gingivitis
Glossodynia
Gout
Haematemesis
Haematoma
Haemorrhoids
Headache
Hemiparesis
Hepatitis
Herpes simplex
Hyperbilirubinaemia
Hyperhidrosis
Hypersensitivity reactions
Hypoaesthesia
Hypocalcaemia
Hypokalaemia
Increase in alkaline phosphatase
Increase in blood urea or creatinine
Increase in haemoglobin
Increase in serum ALT/AST
Increased platelet count
Influenza
Leukocytosis
Loss of balance
Malaise
Menorrhagia
Migraine
Mood changes
Muscle spasm
Myalgia
Myelocyte present
Myelocytosis
Myocardial infarction
Neuropathy
Nocturia
Oesophageal varices
Oropharyngeal pain
Pain
Painful extremities
Palpitations
Paraesthesia
Peripheral oedema
Petechiae
Pneumonia
Prolongation of QT interval
Proteinuria
Pulmonary embolism
Pyrexia
Raised neutrophil count
Rectosigmoid cancer
Renal failure
Respiratory tract infection
Rhinorrhoea
Sinusitis
Skin disorder
Skin pigmentation changes
Sleep disturbances
Somnolence
Speech disturbances
Tachycardia
Thrombocytopenia
Thrombophlebitis
Thrombotic microangiopathy
Tooth ache
Tremor
Urinary tract infections
Vertigo
Visual disturbances
Weight changes
White blood cell count decreased
Effects on Laboratory Tests
As eltrombopag is highly coloured, it may interfere with some laboratory tests as serum discolouration and interference with total bilirubin and creatinine testing have been reported. Re-testing using another method may help in concluding that results are correct if laboratory results and clinical observations are inconsistent.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: January 2023
Reference Sources
Summary of Product Characteristics: Revolade 25mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2022.
Summary of Product Characteristics: Revolade 50mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2022.
Summary of Product Characteristics: Revolade 75mg film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2022.
Summary of Product Characteristics: Revolade oral suspension. Novartis Pharmaceuticals UK Ltd. Revised December 2022.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 January 2023
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.