Revolade
Active
Substance: eltrombopag
olamine
Common Name: eltrombopag
ATC Code: B02BX05
Marketing Authorisation Holder: Novartis Europharm Limited
Active Substance: eltrombopag olamine
Status: Authorised
Authorisation Date: 2010-03-11
Therapeutic Area: Purpura, Thrombocytopenic, Idiopathic
Pharmacotherapeutic Group: Antihaemorrhagics
Therapeutic
Indication
Revolade is
indicated for chronic immune (idiopathic) thrombocytopenic purpura (ITP)
patients aged 1 year and above who are refractory to other treatments (e.g.
corticosteroids, immunoglobulins) (see sections 4.2 and 5.1).
Revolade is
indicated in adult patients with chronic hepatitis C virus (HCV) infection for
the treatment of thrombocytopenia, where the degree of thrombocytopenia is the
main factor preventing the initiation or limiting the ability to maintain
optimal interferon-based therapy (see sections 4.4 and 5.1).
Revolade is
indicated in 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 (see section
5.1).
What is Revolade
and what is it used for?
Revolade is a
medicine that is used for the treatment of:
long-term
immune (idiopathic) thrombocytopenic purpura (ITP), a disease in which the
patient’s immune system destroys the 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. Revolade is used in
patients aged 1 year and above who do not respond to treatment with
medicines such as corticosteroids or immunoglobulins;thrombocytopenia
in adult patients with chronic (long-term) hepatitis C, a disease of the
liver caused by infection with the hepatitis C virus, when the severity of
thrombocytopenia is preventing antiviral therapy;acquired
severe aplastic anaemia (a disease in which the bone marrow does not make
enough blood cells or platelets) in adult patients. Revolade is used in
patients who did not respond to or had received multiple courses of
immunosuppressive therapy (medicines that lower the body’s immune
defences) and cannot receive haematopoietic (blood) stem cell
transplantation.
Revolade
contains the active substance eltrombopag.
How is Revolade
used?
Revolade is
available as tablets (12.5, 25, 50 and 75 mg) and as a powder (25 mg) to
prepare a suspension (a liquid to be taken by mouth). The medicine can only be
obtained with a prescription and treatment should be started and supervised by
a doctor who has experience in treating blood diseases or chronic hepatitis C
and its complications.
The dose depends
on the patient’s age and the disease Revolade is being used to treat; it is
adjusted as needed to maintain the appropriate platelet level. For ITP and
aplastic anaemia, a lower starting dose may be needed in patients of East Asian
descent (such as Chinese, Japanese, Korean or Taiwanese).
Patients should
not take any antacids, dairy products or mineral supplements in the four hours
before and in the two hours after taking Revolade. For more information, see
the package leaflet.
How does
Revolade work?
In the body, a
hormone called ‘thrombopoietin’ stimulates the production of platelets by
attaching to certain targets in the bone marrow. The active substance in
Revolade, eltrombopag, attaches to and stimulates the same receptors as
thrombopoietin. This leads to an increased production of platelets, improving
platelet counts.
What benefits of
Revolade have been shown in studies?
For the
treatment of chronic ITP in adults, Revolade was compared with placebo (a dummy
treatment) in two main studies involving a total of 311 patients who had
previously been treated, but the treatments had not worked or the disease had
come back.
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 effectiveness),
compared with 16% of those who took placebo (6 out of 37). In the second study,
patients taking Revolade were around eight times more likely than those taking
placebo to reach the target platelet count of between 50,000 and 400,000 per
microlitre during the six months of treatment.
In children with
chronic ITP, Revolade was shown to be more effective than placebo in one main
study involving a total of 92 children between 1 and 17 years of age who had
previously received treatment for ITP. This study lasted 13 weeks and looked at
the proportion of patients whose platelet count had increased to at least
50,000 per microlitre for at least 6 out of 8 weeks, between week 5 to 12 of
the study in the absence of rescue medication. This occurred in around 40% of
those taking Revolade (25 out of 63) compared with around 3% (1 out of 29) of
those who took placebo. The study had also an extension phase, in which all
patients received Revolade. This showed that Revolade was also effective at
maintaining adequate levels of platelets in the long term.
For the
treatment of thrombocytopenia associated with hepatitis C, two main studies
involving a total of 1,441 adults were carried out. These compared Revolade
with placebo for allowing the starting and maintenance of antiviral treatment
in patients with hepatitis C whose platelet count was initially too low to
allow starting such treatment (less than 75,000 per microlitre). In both
studies, the main measure of effectiveness was the number of patients whose
blood tests did not show any sign of hepatitis C virus 6 months after the end
of treatment.
In these two
studies, a higher proportion of patients who took Revolade tested negative for
hepatitis C, compared with those who took placebo (23% versus 14% in the first
study, and 19% versus 13% in the second study).
For the
treatment of severe aplastic anaemia, Revolade was studied in 43 patients and
it was not compared with any other medicine. The main measure of effectiveness
was the number of patients who responded to Revolade (whose platelet, red or
white blood cell count remained above pre-set levels) after 12 or 16 weeks of
treatment.
In this study,
40% of patients (17 out of 43) responded to treatment after 12 weeks, and 65%
of responders (11 out of 17) either had a platelet count increase of at least
20,000 per microliter or had a platelet count that was stable without need for
blood transfusions. Preliminary data from a supportive study are consistent
with the result of the main study, with 46% of patients responding to treatment
after 12 weeks.
What are the
risks associated with Revolade?
The most common
side effects with Revolade in adults with chronic ITP and hepatitis C (seen in
more than 1 patient in 10) are headache, anaemia (low red blood cell counts),
decreased appetite, insomnia (difficulty sleeping), cough, nausea (feeling
sick), diarrhoea, pruritus (itching), alopecia (hair loss), myalgia (muscle
pain), pyrexia (fever), fatigue (tiredness), influenza (flu)-like illness,
asthenia (weakness), chills and peripheral oedema (swelling, especially of the
ankles and feet). In addition, in children with ITP the most common side
effects also included colds, nasopharyngitis (inflammation of the nose and
throat), rhinitis (inflammation of the lining of the nose), pain in the belly
or in the mouth and throat, toothache, rash, runny nose and abnormal blood
levels of certain liver enzymes (AST).
In adults with
severe aplastic anaemia the most common side effects included headache,
dizziness, insomnia, cough, dyspnoea (difficulty breathing), pain in the belly
or in the mouth and throat, nausea, diarrhoea, joint pain, muscle spasms, pain
in limbs, fatigue, fever, ecchymosis (discoloration of the skin resulting from
bleeding underneath), abnormal blood levels of certain liver enzymes and runny
nose.
In patients with
thrombocytopenia and advanced chronic hepatitis C who are treated with a
medicine called interferon and Revolade liver problems and thromboembolic
complications (problems with clots in blood vessels) are the most important
serious side effects. In these patients Revolade should only be used if
clinically indicated and patients should then be closely monitored. Bleeding
can also come back after the medicine is stopped.
For the full
list of restrictions and side effects with Revolade, see the package leaflet.
Why has Revolade
been approved?
The European
Medicines Agency decided that Revolade’s benefits are greater than its risks
and recommended that it be given marketing authorisation.
What measures
are being taken to ensure the safe and effective use of Revolade?
Recommendations
and precautions to be followed by healthcare professionals and patients for the
safe and effective use of Revolade have been included in the summary of product
characteristics and the package leaflet.
Other
information about Revolade
The European
Commission granted a marketing authorisation valid throughout the European
Union for Revolade on 11 March 2010.
For more
information about treatment with Revolade, read the package leaflet (also part
of the EPAR) or contact your doctor or pharmacist.
Source: European
Medicines Agency
