DIAPHARM

Symptomatic treatment of severe and/or disabling anxiety manifestations.

Prevention and treatment of delirium tremens and other manifestations of alcohol withdrawal.

Pregnancy

Many data from cohort studies have not shown the occurrence of malformative effects during exposure to benzodiazepines during the 1st trimester of pregnancy. However, in some case-control epidemiological studies, an increase in the occurrence of cleft lip-palate has been observed with benzodiazepines. According to these data, the incidence of cleft lip-palate in newborns would be less than 2/1 000 after exposure to benzodiazepines during pregnancy, whereas the expected rate in the general population is 1/1 000.

In case of taking benzodiazepines at high doses during the 2nd and/or 3rd 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 may 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. Furthermore, 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 away 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 diazepam is not recommended during pregnancy regardless of the term.

In case of prescribing diazepam 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 reassess the benefit of the treatment.

At the end of pregnancy, if it proves truly necessary to start treatment with diazepam, 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.

Driving vehicles is formally not recommended given the possible risk of drowsiness.

Association with other sedative medicines should be not recommended or taken into account in case of driving a car or using machines (see section 4.5).

If the duration of sleep is insufficient, the risk of impaired alertness is even increased.

The most frequently reported adverse effects are fatigue, somnolence and muscular weakness. They are dose-dependent. These effects appear mainly at the start of treatment and tend to disappear in case of prolonged administration.

Nervous system disorders

· Ataxia, dysarthria, speech disorders, headaches, tremors, dizziness, decreased alertness.

· Anterograde amnesia may occur at therapeutic doses, the risk increases with the dose. Amnesia may be associated with abnormal behaviour.

Psychiatric disorders

· Paradoxical reactions such as behavioural disorders, agitation, irritability, aggressiveness, delusional ideas, anger, nightmares, hallucinations, psychoses. Abnormal behaviours may occur with the use of benzodiazepines. If these effects occur, treatment must be stopped. They appear more frequently in children and elderly subjects.

· Confusional state, decreased emotions, depression, modification of libido.

· Prolonged use (even at therapeutic doses) may lead to physical dependence with a rebound phenomenon, or a withdrawal syndrome upon discontinuation of treatment.

· Cases of benzodiazepine abuse have been reported in persons abusing several medicinal or non-medicinal substances (See Section 4.4 Special warnings and precautions for use).

Lesions, intoxications and complications related to procedures

· Cases of falls and fractures have been reported in patients treated with benzodiazepine. This risk increases during concomitant use of sedatives (including alcoholic beverages) and in elderly people.

Gastrointestinal disorders

· Nausea, dry mouth or hypersalivation, constipation and other gastrointestinal disorders.

Eye disorders

· Diplopia, blurred vision.

Vascular disorders

· Hypotension.

Investigations

· An increase in alkaline phosphatases and very rare cases of increase in transaminases have been reported.

· Irregular heart rate.

Renal and urinary disorders

· Incontinence, urinary retention.

Skin and subcutaneous tissue disorders

· Skin eruptions.

Ear and labyrinth disorders

· Vertigo.

Cardiac disorders

· Heart failure.

Respiratory disorders

· Respiratory depression including respiratory failure.

Hepatobiliary disorders

· Very rare cases of jaundice.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorisation 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-sante.gouv.fr .