Adverse reactions : תופעות לוואי

4.8 Undesirable effects
General
The adverse reaction profile for Ropivacaine is similar to those for other long acting local anaesthetics of the amide type. Adverse reactions should be distinguished from the physiological effects of the nerve block itself e.g. Hypotension (a decrease in blood pressure), bradycardia during spinal/ epidural block.

Table of adverse reactions
The following frequencies are used for the description of the occurrence of adverse reactions: 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) and not known (cannot be estimated from the available data ).

System organ class            Frequency                    Undesirable effects Immune system disorder          Rare                       Allergic reactions (anaphylactic reactions , angioneurotic oedema and urticaria

Psychiatric Disorders         Uncommon                     Anxiety
Nervous System Disorders      Common                       Paraesthesia, dizziness, headache Uncommon                     Symptoms of CNS toxicity
(convulsions, grand mal convulsions,
seizures, light headedness, circumoral paraesthesia, numbness of the tongue,
hyperacusis, tinnitus, visual disturbances, dysarthria, muscular twitching, tremor)*, hypoaesthesia
Not known                    Dyskinesia
Cardiac Disorders             Common                       Bradycardia, tachycardia 
Rare                         Cardiac arrest, cardiac arrhythmias
Vascular Disorders            Very common                  Hypotension Common                       Hypertension
Dyskinesia
Uncommon                     Syncope
Respiratory, Thoracic and     Uncommon                     Dyspnoea
Mediastinal Disorders
Dyskinesia
Gastrointestinal Disorders Very common                     Nausea
Common                          Vomiting


Musculoskeletal and               Common                           back pain Connective tissue disorders


Renal and Urinary                Common                           Urinary retention Disorders
General Disorders and            Common                           Temperature elevation, Administration Site                                               Chills Conditions
Uncommon                         Hypothermia


*       These symptoms usually occur because of inadvertent intravascular injection, overdose or rapid absorption, see section 4.9.


Class-related adverse reactions
Neurological complications
Neuropathy and spinal cord dysfunction (e.g. anterior spinal artery syndrome, arachnoiditis, cauda equina), which may result in rare cases of permanent sequelae, have been associated with regional anaesthesia, regardless of the local anaesthetic used.

Total spinal block
Total spinal block may occur if an epidural dose is inadvertently administered intrathecally.

Acute systemic toxicity
Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascular system (CVS). Such reactions are caused by high blood concentration of a local anaesthetic, which may appear due to (accidental) intravascular injection, overdose or exceptionally rapid absorption from highly vascularized areas, see also section 4.4. CNS reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the drugs, both quantitatively and qualitatively.

Central nervous system toxicity
Central nervous system toxicity is a graded response with symptoms and signs of escalating severity.
Initially symptoms such as visual or hearing disturbances, perioral numbness, diziness, light-headedness, tingaling and paraesthesia are seen. Dysarthria, muscular rigidity and muscular twitching are more serious and may precede the onset of generalised convulsions. These signs must not be mistaken for neurotic behaviour. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly during convulsions due to the increased muscular activity, together with the interference with respiration. In severe cases even apnoea may occur. The respiratory and metabolic acidosis increases and extends the toxic effects of local anaesthetics.

Recovery follows the redistribution of the local anaesthetic from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the active 
substance have been injected.

Cardiovascular system toxicity
Cardiovascular toxicity indicates a more severe situation. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics. In volunteers the intravenous infusion of ropivacaine resulted in signs of depression of conductivity and contractility.
Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as benzodiazepines or barbiturates.

Treatment of acute systemic toxicity
(See section 4.9)

Reporting of suspected adverse reactions
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 /and emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com.