Xeplion
Active Substance: paliperidone palmitate
Common Name: paliperidone
ATC Code: N05AX13
Marketing Authorisation Holder: Janssen-Cilag International N.V.
Active Substance: paliperidone palmitate
Status: Authorised
Authorisation Date: 2011-03-04
Therapeutic Area: Schizophrenia
Pharmacotherapeutic Group: Psycholeptics
Therapeutic Indication
Xeplion is indicated for maintenance treatment of
schizophrenia in adult patients stabilised with paliperidone or risperidone.
In selected adult patients with schizophrenia and previous responsiveness to
oral paliperidone or risperidone, Xeplion may be used without prior
stabilisation with oral treatment if psychotic symptoms are mild to moderate
and a long-acting injectable treatment is needed.
What is Xeplion?
Xeplion is a medicine that contains the active
substance paliperidone. It is available as a prolonged-release suspension for
injection in prefilled syringes (25, 50, 75, 100 and 150 mg).
Prolonged-release means that the active substance is released slowly over a few
weeks after being injected.
What is Xeplion used for?
Xeplion is used for the maintenance treatment of
schizophrenia in adults whose disease has already been stabilised on treatment
with paliperidone or risperidone.
Some patients whose symptoms have not yet been
stabilised may still be given Xeplion if they have responded well to oral
paliperidone or risperidone in the past, their symptoms are mild to moderate and
a long-acting injectable treatment is needed.
Schizophrenia is a mental illness that has a number
of symptoms, including disorganised thinking and speech, hallucinations
(hearing or seeing things that are not there), suspiciousness and delusions
(false beliefs).
The medicine can only be obtained with a
prescription.
How is Xeplion used?
Xeplion treatment starts with two injections, one
week apart, to bring the blood levels of paliperidone up, followed by monthly
maintenance injections. The two initial injections are 150 mg on the first
day (day 1) followed by 100 mg on day 8. The monthly maintenance dose
is 75 mg. The dose may be adjusted depending on the medicine’s benefit to
the patient and how the patient tolerates the treatment. The injections on days
1 and 8 are into the upper part of the shoulder (deltoid muscle), while the
maintenance doses can be given in the buttocks or the deltoid muscle. For more
information on the use of Xeplion including how to adjust the doses, see the
summary of product characteristics (also part of the EPAR).
How does Xeplion work?
The active substance in Xeplion, paliperidone, is
an antipsychotic medicine. It is known as an ‘atypical’ antipsychotic because
it is different from the older antipsychotic medicines that have been available
since the 1950s. Paliperidone is an active breakdown product (metabolite) of
risperidone, another antipsychotic medicine that has been used in the treatment
of schizophrenia since the 1990s. In the brain, it attaches to several
different receptors on the surface of nerve cells. This disrupts signals
transmitted between brain cells by ‘neurotransmitters’, chemicals that allow
nerve cells to communicate with each other. Paliperidone acts mainly by
blocking receptors for the neurotransmitters dopamine and 5‑hydroxytryptamine
(also called serotonin), which are involved in schizophrenia. By blocking these
receptors, paliperidone helps to normalise the activity of the brain and reduce
symptoms of the disease.
Paliperidone has been authorised in the European
Union (EU) as Invega since 2007 as an oral treatment for schizophrenia. In
Xeplion, paliperidone has been attached to a fatty acid that allows it to be
released slowly after being injected. This allows for the injection to have a
long duration of action.
How has Xeplion been studied?
Because paliperidone has already been authorised in
the EU as Invega, the company used some of the data from Invega to support the
use of Xeplion.
Six short-term studies were carried out with
Xeplion. Four of the studies, involving 1,774 adults with schizophrenia,
compared Xeplion with placebo (a dummy treatment). Two studies, involving 1,178
patients, compared Xeplion with risperidone long-acting injection (taken with
oral risperidone supplements). The main measure of effectiveness in the studies
was the change in the patients’ symptoms after nine or 13 weeks assessed using
a standard scale for schizophrenia.
Two long-term studies lasting about a year were
carried out with Xeplion. One of the studies, involving 410 adults, compared
Xeplion with placebo. This study looked at how well Xeplion prevented the
relapse of severe symptoms. The second study, involving 749 adults, compared
Xeplion with risperidone long-acting injection (taken with oral risperidone
supplements) and looked at the change in the patients’ symptoms.
What benefit has Xeplion shown during
the studies?
Xeplion was more effective than placebo in reducing
schizophrenia symptoms in the short term. In four short-term studies the
reductions in symptom scores were greater for patients receiving Xeplion than
for those receiving placebo. Xeplion was also shown to be effective in
preventing relapses in the long term, with fewer patients in the Xeplion group
having a relapse compared with the placebo group.
Xeplion was shown to be as effective as risperidone
long-acting injection in reducing schizophrenia in one of the short-term
studies. In two other studies (one long- and one short-term), Xeplion was not
proven to be as effective as risperidone.
What is the risk associated with
Xeplion?
The most frequently reported side effects are
insomnia (difficulty sleeping), headache, anxiety, upper-respiratory-tract
infection (colds), reactions at the site of injection, Parkinsonism
(neurological symptoms including tremor and impaired muscular control),
increased weight, akathisia (restlessness), agitation, somnolence (sleepiness),
nausea, constipation, dizziness, muscle and bone pain, tachycardia (rapid
heartbeat), tremor (shaking), abdominal pain (stomach ache), vomiting
diarrhoea, fatigue (tiredness) and dystonia (involuntary muscle contractions).
Of these, akathisia and somnolence appear to be related to the dose.
For the full list of all side effects reported with
Xeplion, see the package leaflet.
Xeplion must not be given to people who are
hypersensitive (allergic) to paliperidone or any of the other ingredients, or
to risperidone.
Why has Xeplion been approved?
The CHMP noted that the studies comparing Xeplion
with placebo and risperidone showed that the medicine is beneficial to patients
with schizophrenia. Because the medicine is a prolonged-release suspension, it
also has the advantage of being given at monthly intervals. The Committee
decided that Xeplion’s benefits are greater than its risks and recommended that
it be given marketing authorisation.
Other information about Xeplion
The European Commission granted a marketing authorisation
valid throughout the European Union for Xeplion on 4 March 2011.
For more information about treatment with Xeplion,
read the package leaflet (also part of the EPAR) or contact your doctor or
pharmacist.
Source: European Medicines Agency
