RIVOTRIL

In the treatment of epilepsy in adults and children, either as temporary monotherapy, or in association with another anti-epileptic treatment:

· treatment of generalized epilepsies: clonic, tonic, tonic-clonic, absence, myoclonic, atonic seizures, infantile spasms and Lennox-Gastaut syndrome;

· treatment of partial epilepsies: partial seizures with or without secondary generalization.

Pregnancy

Many data from cohort studies have not shown the occurrence of malformative effects during exposure to benzodiazepines during the 1° trimester of pregnancy. However, in some case-control epidemiological studies, an increase in the occurrence of cleft lip-palate was observed with benzodiazepines. According to these data, the incidence of cleft lip-palate in newborns would be less than 2/1000 after exposure to benzodiazepines during pregnancy whereas the expected rate in the general population is 1/1000.

In case of taking benzodiazepines at high doses during the 2° and/or 3° trimesters of pregnancy, a decrease in active fetal movements and a variability of fetal heart rate have been described. Treatment at the end of pregnancy with benzodiazepines, even at low doses, may be responsible in the newborn for signs of impregnation such as axial hypotonia, sucking disorders leading to low weight gain. These signs are reversible, but can last 1 to 3 weeks depending on the half-life of the prescribed benzodiazepine. At high doses, respiratory depression or apneas, and hypothermia may appear in the newborn. Moreover, a neonatal withdrawal syndrome is possible, even in the absence of signs of impregnation. It is characterized notably by hyperexcitability, agitation and tremors of the newborn occurring at a distance from delivery. The onset delay depends on the elimination half-life of the drug and can be significant when this is long.

Given these data, as a precautionary measure, the use of clonazepam is not recommended during pregnancy regardless of the term.

In case of prescribing clonazepam to a woman of childbearing age, she should be warned of the need to contact her doctor if a pregnancy is planned or has started so that he can re-evaluate the benefit of the treatment.

At the end of pregnancy, if it proves truly necessary to start treatment with clonazepam, avoid prescribing high doses and take into account, for the monitoring of the newborn, the previously described effects.

Breastfeeding

The use of this medicine during breastfeeding is not recommended.

After marketing authorization

Immune system disorders: allergic reactions and very rare cases of anaphylaxis or Quincke's edema.

Psychiatric disorders: mood and emotion disorders, confusion state, disorientation, alteration of consciousness, behaviour disorder.

Depression may occur in patients treated with RIVOTRIL, but it may also be associated with the underlying disease.

The following paradoxical reactions have been observed: irritability, aggressiveness, agitation, nervousness, hostility, anxiety, sleep disorders, delusions, anger, nightmares and abnormal dreams, hallucinations, psychoses, hyperactivity, inappropriate behaviour and other behaviour disorders may occur. These manifestations require discontinuation of treatment and are more likely to occur in children and the elderly.

In rare cases, a change in libido may occur.

Drug dependence even at therapeutic doses and withdrawal or rebound symptoms upon discontinuation of treatment (see section 4.4).

Nervous system disorders: impaired concentration, somnolence, slowed reactions, muscle hypotonia, dizziness, ataxia (see section 4.4).

Headaches have been observed in rare cases.

Generalized convulsive seizures have been observed very rarely.

Reversible disorders such as dysarthria, motor incoordination, gait disorder (ataxia) and nystagmus (see section 4.4).

Anterograde amnesia (which may occur at therapeutic doses, the risk increasing proportionally to the dose) and amnestic effects that may be associated with inappropriate behaviour (see section 4.4).

Increased frequency of seizures in certain forms of epilepsy (see section 4.4). Seizures may also appear during prolonged treatment due to decreased efficacy of clonazepam.

Eye disorders: reversible vision disorders (diplopia, blurred vision) (see section 4.4).

Common: nystagmus.

Cardiac disorders: heart failure, including cardiac arrest.

Respiratory, thoracic and mediastinal disorders: respiratory depression (see section 4.4).

Gastrointestinal disorders: the following effects have been reported in rare cases: nausea, epigastric disorders, hypersalivation.

Hepatic manifestations: some cases of increased liver enzymes have been reported.

Skin and subcutaneous tissue disorders: the following effects may occur in rare cases: urticaria, pruritus, rash, transient hair loss, pigmentation changes.

Musculoskeletal and systemic disorders: muscle weakness, muscle hypotonia (see section 4.4).

Renal and urinary disorders: in rare cases, urinary incontinence or urinary retention may occur.

Reproductive system and breast disorders: in rare cases, erectile dysfunction may occur.

General disorders and administration site abnormalities: fatigue, lassitude (see section 4.4).

Injuries, intoxications and complications related to procedures: an increase in the risk of falls and fractures has been reported in patients treated with benzodiazepines. This risk increases during concomitant use of sedatives (including alcoholic beverages) and in elderly people.

Investigations: in rare cases, thrombocytopenia, leucopenia and exceptionally anaemia may occur.

Paediatric population

Endocrine disorders: isolated cases of reversible development of early secondary sexual characteristics (incomplete precocious puberty) .

Respiratory, thoracic and mediastinal disorders: in infants and young children, increase in saliva production and bronchial secretion (see section 4.4).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions 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 reaction 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 .