RISPERDAL ORO

RlSPERlDONE VIATRIS is indicated for the treatment of schizophrenia.

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

RlSPERlDONE VIATRIS 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.

RlSPERlDONE VIATRIS is indicated for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from the age of 5 years 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 behaviours require pharmacological treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment programme, 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 in pregnant women. Risperidone did not show teratogenic effects in animal studies but other types of reproductive toxicity were observed (see section 5.3). The potential risk for humans is unknown.

Neonates exposed to antipsychotics (including risperidone) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal syndrome and/or withdrawal symptoms that may vary in severity and duration after delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorders. Consequently, neonates should be monitored carefully (see section 4.8).

RlSPERlDONE VIATRIS should not be used during pregnancy unless clearly necessary. If discontinuation is necessary during pregnancy, it should not be done abruptly.

Breastfeeding

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

Fertility

As with other drugs that are antagonists of dopamine D2 receptors, risperidone increases prolactin levels.

Hyperprolactinemia may inhibit hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. Subsequently, this may inhibit reproductive function by impairing gonadal steroidogenesis in both male and female patients.

No relevant effects were observed in non-clinical studies.

RISPERIDONE VIATRIS 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 effects (AEs) (frequency ≥ 10 %) are: parkinsonism, sedation/somnolence, headache, and insomnia.

Adverse effects that appeared dose-dependently included parkinsonism and akathisia.

The following AEs are all the AEs reported during clinical trials and after marketing by category of frequency estimated from clinical trials of risperidone. The following terms and frequencies are used: very frequent (≥ 1/10), frequent (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), and undetermined frequency (cannot be estimated from available clinical trial data).

Within each frequency group, adverse effects are presented in descending order of severity.

a Hyperprolactinaemia may in some cases lead to gynecomastia, menstrual disorders, amenorrhea, anovulation, galactorrhea, fertility disorder, decreased libido and erectile dysfunction.

b In controlled versus placebo 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 in all clinical trials was 0.43 % in all subjects treated with risperidone.

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

d Extrapyramidal disorder may include: parkinsonism (hypersalivation, musculoskeletal rigidity, parkinsonism, salivation, (phenomenon of) cogwheeling, bradykinesia, hypokinesia, frozen facial aspect, muscle contraction, akinesia, neck rigidity, muscle rigidity, parkinsonian gait, and abnormal eyelid reflex), parkinsonian resting tremor, akathisia (akathisia, restlessness, hyperkinesia, and restless legs syndrome), tremor, dyskinesia (dyskinesia, muscle spasm, choreoathetosis, athetosis, and myoclonus), dystonia.

Dystonia includes dystonia, hypertonia, torticollis, involuntary muscle spasms, muscle contracture, blepharospasm, ocular revolution, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurothotonus, tongue spasm, and trismus. It is to be noted that symptoms of a wider spectrum have been included, which do not necessarily have an extrapyramidal origin.

Insomnia includes: initial insomnia, middle of the night insomnia.

Convulsion includes: Grand mal seizure; menstrual disorder includes: irregular menstruation, oligomenorrhea; oedema includes: generalized 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) apply to each other. In addition to the adverse effects above, the following adverse effects have been observed during the use of paliperidone-based products and may be expected with risperidone.

Cardiac disorders: 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 torsades 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 increase

Percentages of adult schizophrenic patients treated with oral risperidone and placebo and reaching the weight gain criterion of ≥ 7 % were compared in a pooled analysis of placebo-controlled trials lasting 6 to 8 weeks, showing a significantly higher incidence of weight gain in the oral risperidone group (18 %) compared to placebo (9 %). In a pool of placebo-controlled clinical studies lasting 3 weeks in adults presenting with an acute manic episode, the incidence of weight gain ≥7 % at the end of the study was comparable in the oral risperidone (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 presenting with conduct disorders and other disruptive behavior 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 the order of 3 to 5 kg per year is maintained in girls, while boys gain approximately 5 kg per year.

Additional information on particular populations

The adverse effects which have been reported with a higher incidence in elderly demented patients or in pediatric patients than in the adult population are described below:

Elderly demented patients

Transient ischemic attacks and strokes are adverse effects reported in clinical trials with a frequency of 1,4 % and 1,5 % respectively, in elderly demented patients. The following adverse effects have also been reported with a frequency ≥ 5 % in elderly demented patients and with a frequency at least double the frequency observed in other adult populations: urinary tract infection, peripheral edema, lethargy and cough.

Pediatric patients

In general, the types of adverse effects expected in children are similar to those observed in adults.

The following adverse effects have been reported with a frequency ≥ 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, sensation of dizziness, cough, pyrexia, tremor, diarrhea and enuresis.

The long-term effects of treatment with risperidone on sexual maturation and height have not been sufficiently studied (see section 4.4 "Pediatric population").

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorisation of the medicinal product is important. It allows continued 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-sante.gouv.fr .