PRISDAL

RISPERDAL is indicated for the treatment of schizophrenia.

RISPERDAL is indicated for the treatment of moderate to severe manic episodes associated with bipolar disorders.

RISPERDAL is indicated for the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others.

RISPERDAL is indicated for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from 5 years of age and adolescents with subaverage intellectual functioning or mental retardation diagnosed in accordance with DSM-IV criteria, in whom the severity of aggressive or other disruptive behaviors require pharmacological treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment program, including psychosocial and educational interventions. It is recommended that risperidone be prescribed by a specialist in child neurology and child and adolescent psychiatry or physicians familiar with the treatment of conduct disorder of children and adolescents.

Pregnancy

There are no adequate data on the use of risperidone during pregnancy.

Risperidone has not shown teratogenic effects in studies conducted in animals but other types of reproductive toxicity have been observed (see section 5.3). The potential risk in humans is unknown.

Newborns exposed to antipsychotics (including RISPERDAL) during the third trimester of pregnancy present a risk of adverse reactions including extrapyramidal symptoms and/or withdrawal symptoms, which may vary in terms of severity and duration after childbirth. The following reactions have been reported: agitation, hypertonia, hypotonia, tremors, somnolence, respiratory distress, feeding disorder. Consequently, newborns must be closely monitored. RISPERDAL should not be used during pregnancy unless manifestly necessary. When discontinuation is necessary during pregnancy, it must not be carried out suddenly.

Breastfeeding

In animal studies, risperidone and 9-hydroxy-risperidone are excreted in milk. It has been shown that risperidone and 9-hydroxy-risperidone are also excreted in breast milk in small quantities. There are no data available on adverse effects in the breastfed infant. Consequently, the benefits of breastfeeding should be weighed against the potential risks to the child.

Fertility

As with other D2 dopamine receptor antagonists, RISPERDAL increases prolactin levels. Hyperprolactinemia may inhibit hypothalamic GnRH, leading to a decrease in the secretion of pituitary gonadotropins. Subsequently, this may inhibit reproductive function by altering gonadal steroidogenesis in male and female patients.

No relevant effect has been observed in non-clinical studies.

RISPERDAL may have a minor or moderate influence on the ability to drive and use machines due to potential effects on the nervous system and vision (see section 4.8). Consequently, patients must be informed not to drive or use machines until their individual sensitivity is known.

The most frequently reported adverse reactions (frequency ³ 10%) are: Parkinsonism, sedation/somnolence, headache, and insomnia.

Dose-dependent adverse reactions included parkinsonism and akathisia.

The following adverse reactions are all adverse reactions reported with risperidone during clinical trials and post-marketing by frequency category estimated from clinical trials of RISPERDAL. The following terms and frequencies are used: very common ( ³ 1/10), common ( ³ 1/100, <1/10), uncommon ( ³ 1/1 000, <1/100), rare ( ³ 1/10 000, <1/1 000), very rare (<1/10 000), and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

a Hyperprolactinaemia can in some cases lead to gynaecomastia, menstrual disturbances, amenorrhoea, anovulation, galactorrhoea, fertility disorder, decreased libido, erectile dysfunction.

b In placebo-controlled trials, diabetes was reported in 0,18% of subjects treated with risperidone compared to a rate of 0,11% in the placebo group. The overall incidence from all clinical trials was 0,43% in all subjects treated with risperidone.

c Not observed during RISPERDAL clinical studies but observed in the post-marketing environment with risperidone.

d Extrapyramidal disorder may include: Parkinsonism (salivary hypersecretion, musculoskeletal stiffness, parkinsonism, drooling, cogwheel rigidity, bradykinesia, hypokinesia, masked facies, muscle twitching, akinesia, nuchal rigidity, muscle rigidity, parkinsonian gait and abnormal eyelid reflex, resting parkinsonian tremor), akathisia (akathisia, restlessness, hyperkinesia, and restless leg syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis, and myoclonus), dystonia.

Dystonia includes: dystonia, hypertonia, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, oculogyration, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurothotonus, tongue spasm, and trismus. It is noted that a broader spectrum of symptoms is included, which do not necessarily have an extrapyramidal origin.

Insomnia includes: initial insomnia, middle insomnia. Convulsion includes: Grand mal convulsion; menstrual disorder includes: irregular menstruation, oligomenorrhoea; oedema includes: generalised oedema, peripheral oedema, pitting oedema.

Adverse effects observed with paliperidone formulations

Paliperidone is the active metabolite of risperidone, therefore, the adverse effect profiles of these compounds (including both oral and injectable formulations) are applicable to each other. In addition to the above adverse effects, the following adverse effects have been observed with the use of paliperidone-containing products and can be expected with RISPERDAL.

Cardiac disorders: Postural orthostatic tachycardia syndrome

Class effects

As with other antipsychotics, very rare cases of QT prolongation have been reported post-marketing with risperidone. Other class cardiac effects reported with antipsychotics that prolong the QT interval include ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and torsade de pointes.

Venous thromboembolism

Cases of venous thromboembolism, including cases of pulmonary embolism as well as deep vein thrombosis, have been reported with antipsychotics (frequency unknown).

Weight gain

The percentages of adult schizophrenia patients treated with RISPERDAL and placebo meeting the weight gain criterion ³ 7% were compared in a pooled analysis of placebo-controlled trials of 6 to 8 weeks duration, showing a significantly higher incidence of weight gain in the RISPERDAL group (18%) compared to placebo (9%). In a pool of placebo-controlled clinical studies of 3 weeks duration in adults with acute manic episodes, the incidence of weight gain ³ 7% at endpoint was comparable in the RISPERDAL (2,5%) and placebo (2,4%) groups, and was slightly higher in the active control group (3,5%).

In a population of children and adolescents with conduct and other disruptive behaviour disorders, in long-term studies, weight gain was on average 7,3 kg after 12 months of treatment. The expected weight gain for normal children aged 5-12 years is 3 to 5 kg per year. Between 12-16 years, a weight gain of about 3 to 5 kg per year is maintained in girls, while boys gain about 5 kg per year.

Additional information on special populations

Adverse effects that have been reported with a higher incidence in elderly patients with dementia or in paediatric patients than in the adult population are described below:

Elderly patients with dementia

Transient ischaemic attacks and cerebrovascular accidents are adverse effects reported in clinical trials with a respective frequency of 1,4% and 1,5%, in elderly patients with dementia. The following adverse effects have also been reported with a frequency ³ 5% in elderly patients with dementia and with a frequency at least double the frequency observed in other adult populations: urinary tract infection, peripheral oedema, lethargy, and cough.

Paediatric population

As a general rule, it can be assumed that adverse effects in children are similar in nature to those observed in adults.

The following adverse effects were reported with a frequency of ³ 5% in pediatric patients (5 to 17 years) and with a frequency at least double the frequency observed in clinical trials conducted in adults: somnolence/sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infections, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, and enuresis.

The effect of long-term treatment with risperidone on sexual maturation and height has not been adequately studied (see section 4.4, subsection “Pediatric population”).

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorization of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: www.signalement.social-sante.gouv.fr .