Ropivacaine Other names: Ropivacaine hydrochloride

Ropivacaine hydrochloride is metabolised in the liver and should therefore be used with caution in patients with severe liver disease. Repeated doses may need to be reduced due to delayed elimination.

Patients treated with anti-arrhythmic drugs class III (e.g. amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive.

Ropivacaine hydrochloride should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, e.g. certain antiarrhythmics, such as lidocaine and mexiletine, since the systemic toxic effects are additive. Simultaneous use of ropivacaine with general anaesthetics or opioids may potentiate each other’s (adverse) effects.

Normally there is no need to modify the dose in patients with impaired renal function when used for single dose or short-term treatment. Acidosis and reduced plasma protein concentration, frequently seen in patients with chronic renal failure, may increase the risk of systemic toxicity.

Apart from epidural administration for obstetrical use, there are no adequate data on the use of ropivacaine in human pregnancy. Experimental animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.

There is no data available concerning the excretion of ropivacaine into human breast milk.

Fertility

There are no data available concerning the fertility.

No studies on the effects on the ability to drive and use machines have been performed. Depending on the dose, local anaesthetics may have a minor influence on mental function and coordination even in the absence of overt CNS toxicity and may temporarily impair locomotion and alertness.

The adverse reaction profile for Ropivacaine is similar to those for other long acting local anaesthetics of the amide type. Adverse drug reactions should be distinguished from the physiological effects of the nerve block itself e.g. hypotension and bradycardia during spinal/epidural block, and events caused by needle puncture (e.g., spinal haematoma, postdural puncture headache, meningitis and epidural abscess).

The most frequently reported adverse reactions, nausea, vomiting and hypotension, are very frequent during anaesthesia and surgery in general and it is not possible to distinguish those caused by the clinical situation from those caused by the medicinal product or the block.

The percentage of patients that can be expected to experience adverse reactions varies with the route of administration of Ropivacaine. Systemic and localised adverse reactions of Ropivacaine usually occur because of excessive dosage, rapid absorption, or inadvertent intravascular injection.

The frequency of undesirable effects listed below is defined using the following convention: 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), Not known (cannot be estimated from the available data).

Psychiatric disorders

Uncommon: Anxiety

Nervous system disorders

Common: Headache, paraesthesia, dizziness

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^a

Common: Hypertension

Uncommon: Syncope

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Gastrointestinal disorders

Very common: Nausea

Common: Vomiting^b

Renal and urinary disorders

Common: Urinary retention

General disorders and administration site conditions

Common: Chills

Uncommon: Hypothermia

Rare: Allergic reactions (anaphylactic reactions, angioneurotic oedema and urticaria)

Musculoskeletal and Connective Tissue

Common: Back pain

^* These symptoms usually occur because of inadvertent intravascular injection, overdose or rapid absorption.
^a Hypotension is less frequent in children (>1/100).
^b Vomiting is more frequent in children (>1/10).

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 vascularised areas. CNS reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the active substance, both quantitatively and qualitatively.

Central nervous system

Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. Initially symptoms such as visual or auditory disturbances, perioral numbness, dizziness, light-headedness, tingling 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 an underlying neurological disease. Unconsciousness and tonic-clonic (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 active substance from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the medicinal product have been injected.

Cardiovascular 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 hydrochloride 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 medicinal products such as benzodiazepines or barbiturates.

Paediatric population

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults except for hypotension which happens less often in children (<1 in 10) and vomiting which happens more often in children (>1 in 10).

In children, early signs of local anaesthetic toxicity may be difficult to detect since they may not be able to verbally express them.