Adverse reactions : תופעות לוואי

4.8    Undesirable effects

The evaluation of undesirable effects is based on the following frequency data: 
Very common                    > 1/10
Common                         > 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
Unknown
Cannot be estimated from the available data

Undesirable effects of diazepam are frequent – depending on the individual sensitivity of the patient and the dose used, and of varying intensity, and appear primarily at the beginning of the treatment. They can often be reduced or avoided by careful individual adjustment of the daily dose or they can decrease in the course of the therapy.

Metabolic and nutritional disorders
Rare:                       Appetite increase

Psychiatric disorders
Common:                        Depression
Uncommon:                      Change in sex drive (increased or decreased libido)

If hallucinations and psychoses occur as well as "paradoxical" reactions, such as acute states of excitation, excitability, irritability, aggressive behavior, restlessness (agitation), nervousness, hostility, anxiety states, suicidality , insomnia, rage attacks, increased muscle spasms, nightmares and vivid dreams, the treatment with diazepam should be terminated (see Section 4.4).

In patients with pre-existing depressive disorder, the symptoms can be enhanced (see Section 4.4).

Diazepam possesses a primary potential for dependency. There is a risk of dependency even with daily use over a few weeks. This applies not only to misuse intake of particularly high doses, but also to the therapeutic dose range (see Section 4.4).

When diazepam therapy is stopped, discontinuation phenomena (e.g. rebound phenomena) or withdrawal symptoms are possible (see Section 4.4).
During treatment with benzodiazepines, it should generally be taken into account that withdrawal symptoms can appear if the patient switches to a benzodiazepine with a markedly shorter elimination half-life.

Nervous system disorders
Common:              Undesirably high daytime sedation such as fatigue (somnolence, lassitude, drowsiness, delayed reaction time), sensation of dizziness, headache,
ataxia, confusion, anterograde amnesia
Uncommon:            Tremor

In the morning following evening administration, hangover effects (concentration disturbances and residual fatigue) can impair the reaction capacity.

Anterograde amnesia can appear during benzodiazepine treatment with therapeutic doses. The risk of appearance of this undesirable effect increases with higher doses.
Amnesic effects may be related to inappropriate behavior (see Section 4.4).

At high doses and during prolonged use of diazepam, reversible disturbances, such as slow or slurred speech (articulation disturbances) and unsteadiness of movement and gait are possible.

Eye disorders
At high doses and during prolonged use of diazepam, reversible visual disturbances (diplopia, blurred vision, nystagmus) can occur.

Ear and labyrinth disorders
Not known:            Vertigo

Cardiac disorders:
Rare:                  Bradycardia
Not known:             Arrhythmia, heart failure including cardiac arrest 
Vascular disorders:
Uncommon:              Hypotension, circulatory collapse

Respiratory, thoratic and mediastinal disorders
Rare:                  Laryngospasm, chest pain, respiratory depression including respiratory arrest.


The respiratory depression effect can appear in a more severe form if there is airway obstruction and in patients with brain injury. This needs to be borne in mind in particular in the case of concomitant combination with other centrally acting substances(see Sections 4.4 and 4.5).

Gastrointestinal disorderss
Uncommon:             Nausea, vomiting, epigastric complaints,
constipation, diarrhea, dry mouth, increased salivation.

Hepatobiliary disorders
Rare:                 Jaundice
Skin and subcutaneous tissue disorders
Uncommon:            Allergic skin reaction (e.g. itching, urticaria, skin rash)

Musculoskeletal and conjunctive tissue disorders
Not known:           Muscle weakness

Renal and urinary disorders
Uncommon:             Urinary retention, incontinence
Reproductive system and breast disorders
Rare:                Menstrual cycle disorders in women

General diorders and administration site conditionsRarely, hypersensitivity reactions caused by benzyl alcohol can occur.

Not known              Risk of falls
In elderly patients on benzodiazepine treatment, an increased risk of falls and fractures was observed.

During long-term and repeated use of diazepam, development of tolerance is possible.

Rapid I.V. administration, can cause a fall in blood pressure, cardiac arrest and respiratory arrest by influencing cardiovascular and respiratory function.

In case of injection into a vein that is too small, irritation of the venous wall (as well as thrombophlebitis) is possible. Especially in the case of a too rapid injection, a burning sensation and pain in the area of the injection site can occur.

In rare cases, intramuscular injections can lead to irritation and pain at the injection site (see Section 4.2).

Tests
Not known               Elevated transaminase and alkali phosphatase values

The following have also appeared during treatment with benzodiazepines: EEG alterations, blood count changes including agranulocytosis, blurred vision, double vision, fever, stupor, orientation disorders and euphoria.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/