o

EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/734452/2012

EMEA/H/C/000471

EPAR summary for the public

Abilify

aripiprazole

This is a summary of the European public assessment report (EPAR) for Abilify. 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 Abilify.

What is Abilify?

Abilify is a medicine that contains the active substance aripiprazole. It is available as tablets (5 mg, 10

mg, 15 mg and 30 mg), orodispersible tablets (tablets that dissolve in the mouth; 10, 15 and 30 mg),

an oral solution (1 mg/ml) and a solution for injection (7.5 mg/ml).

What is Abilify used for?

Abilify is used in patients with the following mental illnesses:

•    schizophrenia, a mental illness with a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (false beliefs). Abilify is used in patients aged 15 years or over;

•    bipolar I disorder, a mental illness in which patients have manic episodes (periods of abnormally high mood), alternating with periods of normal mood. They may also have episodes of depression. Abilify is used in adults to treat moderate to severe manic episodes and to prevent new manic episodes in adults who have responded to the medicine in the past. Abilify is also used for up to 12 weeks to treat moderate to severe manic episodes in patients aged 13 years or over.

The injection is used for the rapid control of agitation or disturbed behaviour in adults, in situations

where it is not appropriate to give the medicine by mouth.

The medicine can only be obtained with a prescription.

7 Westferry Circus • Canary Wharf • London E14 4HB • United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail info@ema.europa.eu Website www.ema.europa.eu

© European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged.

For schizophrenia, the recommended starting dose is 10 or 15 mg by mouth per day in adults, followed by a 'maintenance' dose of 15 mg once a day. In patients aged between 15 and 17 years, the starting dose is 2 mg a day, which is gradually increased to the recommended dose of 10 mg once a day.

For treating manic episodes in bipolar disorder, the recommended starting dose in adults is 15 mg by mouth once a day, either on its own or in combination with other medicines. To prevent manic episodes in adults, the same dose should be continued.

For treating manic episodes in patients aged between 13 and 17 years, the starting dose is 2 mg a day, which is gradually increased to the recommended dose of 10 mg once a day. Treatment must not last longer than 12 weeks.

The oral solution or orodispersible tablets can be used in patients who have difficulty swallowing tablets. The injection is only for short-term use in adults and the usual dose is 9.75 mg as a single injection into the shoulder or buttock muscle, but effective doses range between 5.25 and 15 mg. A second injection can be given from two hours after the first if necessary, but no more than three injections should be given in any 24-hour period.

The dose should be adjusted in patients who are taking other medicines that are broken down in the same way as Abilify. For more information, see the package leaflet.

How does Abilify work?

The active substance in Abilify, aripiprazole, is an antipsychotic medicine. Its exact mechanism of action is unknown, but it attaches to several different receptors on the surface of nerve cells in the brain. This disrupts signals transmitted between brain cells by 'neurotransmitters', chemicals that allow nerve cells to communicate with each other. Aripiprazole is thought to act mainly by being a 'partial agonist' for the receptors for the neurotransmitters dopamine and 5-hydroxytryptamine (also called serotonin). This means that aripiprazole acts like dopamine and 5-hydroxytryptamine by activating these receptors, but less strongly than the neurotransmitters. Since dopamine and 5-hydroxytryptamine are involved in schizophrenia and bipolar disorder, aripiprazole helps to normalise the activity of the brain, reducing psychotic or manic symptoms and preventing them from returning.

How has Abilify been studied?

For the treatment of schizophrenia, there were three main short-term studies lasting four to six weeks, which involved 1,203 adults and compared Abilify tablets with placebo (a dummy treatment). The effectiveness of Abilify in preventing symptoms from returning was assessed in three studies lasting up to a year, two of which used haloperidol (another antipsychotic medicine) as a comparator. Abilify tablets were also compared with placebo in one study involving 302 patients aged between 13 and 17 years. The solution for injection was compared with placebo over a period of two hours in two studies involving 805 adults with schizophrenia or related conditions who were experiencing symptoms of agitation. All of the studies measured the change in the patient's symptoms using a standard scale for schizophrenia.

For the treatment of bipolar disorder, there were eight main studies looking at Abilify taken by mouth in adults. Five of these compared Abilify with placebo over three weeks in a total of 1,900 adults, two of which continued for a further nine weeks to look at the maintenance of the effect and used haloperidol and lithium (another antipsychotic medicine) as comparators. The sixth study compared

Ability with haloperidol over 12 weeks in 347 adults, and the seventh compared Abilify with placebo in the prevention of recurrence in 160 adults whose manic symptoms had already been stabilised using Abilify. The eighth study looked at the effect of adding Abilify or placebo to existing treatment with lithium or valproate (another antipsychotic medicine) in 384 adults. Abilify was also compared with placebo in one study involving 296 children and adolescents.

Abilify solution for injection was compared with lorazepam (another antipsychotic medicine) and placebo over two hours in one study involving 301 patients experiencing symptoms of agitation.

All of these studies looked at the change in symptoms using a standard scale for bipolar disorder or at the number of patients who responded to treatment.

The company also carried out studies looking at the absorption of the orodispersible tablets and oral solution by the body.

What benefit has Abilify shown during the studies?

When used to treat schizophrenia, Abilify was more effective than placebo in the short-term adult studies. In the long-term studies, Abilify was more effective than placebo, and as effective as haloperidol, after up to a year of treatment. Abilify was also more effective than placebo over six weeks in the study of adolescents, and the effect of Abilify was maintained for at least six months in patients aged over 15 years. In both studies of the solution for injection, patients receiving Abilify had a greater reduction in symptoms of agitation than those receiving placebo.

When used to treat bipolar disorder, Abilify was more effective than placebo at reducing manic symptoms in four of the five short-term studies in adults. Abilify also had a similar effect to haloperidol and to lithium over three weeks. This effect was maintained for up to 12 weeks. Abilify was also more effective than placebo at preventing manic episodes returning in previously treated adults for up to 74 weeks, and when it was used as an add-on to existing treatment. In the study in children and adolescents, Abilify was also more effective than placebo at reducing the manic symptoms of bipolar disorder.

Injections of Abilify were also more effective than placebo in reducing the symptoms of agitation, and were of similar effectiveness to lorazepam.

What is the risk associated with Abilify?

In adults, the most common side effects when taking Abilify by mouth (seen in between 1 and 10 patients in 100) are restlessness, insomnia (difficulty sleeping), anxiety, extrapyramidal disorder (uncontrolled twitching or jerking), akathisia (a constant urge to move), tremor (shaking), dizziness, somnolence (sleepiness), sedation (drowsiness), headache, blurred vision, dyspepsia (heartburn), vomiting, nausea (feeling sick), constipation, salivary hypersecretion (increased production of saliva) and fatigue (tiredness). The side effects are similar in adolescents, but somnolence, sedation, extrapyramidal disorder, akathisia and fatigue were reported very commonly (in more than 1 in 10 patients).

The most common side effects with the injection (seen in between 1 and 10 patients in 100) are somnolence, dizziness, headache, akathisia, nausea and vomiting.

For the full list of all side effects and restrictions, see the package leaflet.

The CHMP decided that Abilify'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 Abilify?

A risk management plan has been developed to ensure that Abilify is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Abilify, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Abilify will provide educational materials to be supplied to patients or their caregivers and to doctors to explain the safe use of the medicine in patients between 13 and 17 years.

Other information about Abilify

The European Commission granted a marketing authorisation valid throughout the European Union for Abilify on 4 June 2004.

The full EPAR for Abilify 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 Abilify, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 11-2013.

Abilify

EMA/734452/2012

Page 4/4