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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/472922/2012

EMEA/H/C/002105

EPAR summary for the public

Xeplion

paliperidone

This is a summary of the European public assessment report (EPAR) for Xeplion. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Xeplion.

What is Xeplion?

Xeplion is a medicine that contains the active substance paliperidone. It is available as a prolonged-release suspension for injection in pre-filled 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

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(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 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 longterm, 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.

The full EPAR for Xeplion can be found on the Agency's website ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Xeplion, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 07-2012.

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Xeplion

EMA/472922/2012