Section 2
Addition of new text:
Naropin® 7.5 mg/ml:
1 ml solution for injection contains ropivacaine hydrochloride monohydrate equivalent to 7.5 mg ropivacaine hydrochloride.
1 ampoule of 10 ml or 20 ml solution for injection contains ropivacaine hydrochloride monohydrate equivalent to 75 mg and 150 mg ropivacaine hydrochloride respectively.
For excipients, see section 6.1.
Section 3
Addition of new text:
Clear, colourless solution.
Section 4.2
Under the heading Posology: addition of new text:
Adults and children above 12 years of age:
Also, in the table there is a reference (3) with a footnote at the end of the table for explanation, as follows:
(3) The dose for a major nerve block must be adjusted according to site of administration and patient status. Interscalene and supraclavicular brachial plexus blocks may be associated with a higher frequency of serious adverse reactions, regardless of the local anaesthetic used, (see section 4.4. Special warnings and special precautions for use).
Section 4.3
Addition of new text:
Hypersensitivity to ropivacaine or to other local anaesthetics of the amide type.
And deletion of text:
Naropin solutions are contraindicated in patients with known hypersensitivity to anaesthetics of the amide type.
Section 4.4
Current text:
Regional anaesthetic procedures should always be performed in a properly equipped and staffed area. Equipment and drugs necessary for monitoring and emergency resuscitation should be immediately available. For emergency medication, patients receiving major blocks should have an intravenous line inserted before the blocking procedure. The clinician responsible should be appropriately trained and familiar with diagnosis and treatment of side effects, systemic toxicity and other complications Convulsions have occurred most often after brachial plexus block and epidural block. This is likely to be the result of either accidental intravascular injection or rapid absorption from the injection site.
Certain local anaesthetic procedures, such as injections in the head and neck regions, may be associated with a higher frequency of serious adverse reactions, regardless of the local anaesthetic used. Caution is required to prevent injections in inflamed areas.
Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver disease or severe renal dysfunction require special attention, although regional anaesthesia is frequently indicated in these patients.
Ropivacaine 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. 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.
Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during epidural anaesthesia, regardless of the local anaesthetic used.
Prolonged administration of ropivacaine should be avoided in patients concomitantly treated with strong CYP1A2 inhibitors, such as fluvoxamine and enoxacin, see 4.5.
A possible cross-hypersensitivity with other amide-type local anaesthetics should be taken into account.
New text:
Regional anaesthetic procedures should always be performed in a properly equipped and staffed area. Equipment and drugs necessary for monitoring and emergency resuscitation should be immediately available. Patients receiving major blocks should be in an optimal condition and have an intravenous line inserted before the blocking procedure. The clinician responsible should take the necessary precautions to avoid intravascular injection (see section 4.2 Posology and method of administration) and be appropriately trained and familiar with diagnosis and treatment of side effects, systemic toxicity and other complications (see section 4.8 Undesirable effects and 4.9 Overdose) such as inadvertent subarachnoid injection, which may produce a high spinal block with apnoea and hypotension. Convulsions have occurred most often after brachial plexus block and epidural block. This is likely to be the result of either accidental intravascular injection or rapid absorption from the injection site.
Major peripheral nerve blocks may imply the administration of a large volume of local anaesthetic in highly vascularized areas, often close to large vessels where there is an increased risk of intravascular injection and/or rapid systemic absorption, which can lead to high plasma concentrations.
Certain local anaesthetic procedures, such as injections in the head and neck regions, may be associated with a higher frequency of serious adverse reactions, regardless of the local anaesthetic used. Caution is required to prevent injections in inflamed areas.
Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver disease or severe renal dysfunction require special attention, although regional anaesthesia is frequently indicated in these patients. 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 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. 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.
Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during epidural anaesthesia, regardless of the local anaesthetic used.
Prolonged administration of ropivacaine should be avoided in patients concomitantly treated with strong CYP1A2 inhibitors, such as fluvoxamine and enoxacin, see 4.5.
A possible cross-hypersensitivity with other amide-type local anaesthetics should be taken into account.
This medicinal product contains maximum 3.7 mg sodium per ml. To be taken into consideration by patients on a controlled sodium diet.
Section 4.5
Current text:
Naropin should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, e.g. certain antiarrhythmics, since the toxic effects are additive. Simultaneous use of Naropin with general anaesthetics or opioids may potentiate each others (adverse) effects. Cytochrome P450 (CYP) 1A2 is involved in the formation of 3-hydroxy-ropivacaine, the major metabolite. In vivo, the plasma clearance of ropivacaine was reduced by 70% during co‑administration of fluvoxamine, a selective and potent CYP1A2 inhibitor. Thus strong inhibitors of CYP1A2, such as fluvoxamine and enoxacin given concomitantly during prolonged administration of Naropin, can interact with Naropin. Prolonged administration of ropivacaine should be avoided in patients concomitantly treated with strong CYP1A2 inhibitors, see also 4.4.
In vivo, the plasma clearance of ropivacaine was reduced by 15% during co‑administration of ketoconazole, a selective and potent inhibitor of CYP3A4. However, the inhibition of this isozyme is not likely to have clinical relevance.
In vitro, ropivacaine is a competitive inhibitor of CYP2D6 but does not seem to inhibit this isozyme at clinically attained plasma concentrations.
New text
Naropin 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 Naropin with general anaesthetics or opioids may potentiate each others (adverse) effects. Specific interaction studies with ropivacaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution is advised (see also section 4.4 Special warnings and special precautions for use).
Cytochrome P450 (CYP) 1A2 is involved in the formation of 3-hydroxy-ropivacaine, the major metabolite. In vivo, the plasma clearance of ropivacaine was reduced by up to 77% during co‑administration of fluvoxamine, a selective and potent CYP1A2 inhibitor. Thus strong inhibitors of CYP1A2, such as fluvoxamine and enoxacin given concomitantly during prolonged administration of Naropin, can interact with Naropin. Prolonged administration of ropivacaine should be avoided in patients concomitantly treated with strong CYP1A2 inhibitors, see also 4.4.
In vivo, the plasma clearance of ropivacaine was reduced by 15% during co‑administration of ketoconazole, a selective and potent inhibitor of CYP3A4. However, the inhibition of this isozyme is not likely to have clinical relevance.
In vitro, ropivacaine is a competitive inhibitor of CYP2D6 but does not seem to inhibit this isozyme at clinically attained plasma concentrations.
Section 4.6
Addition of new text under heading: Pregnancy
Current text
Apart from obstetrical use, there are no adequate data on the use of ropivacaine in pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fœtal development, parturition or postnatal development (see section 5.3).
New text:
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/fœtal development, parturition or postnatal development (see section 5.3 Preclinical safety data).
Section 4.8
Addition of new text within Table of adverse drug reactions
Common (>1/100) General Disorder and Administration Site Conditions back pain
Addition of next text - as follows
Uncommon (>1/1,000) Psychiatric Disorders Anxiety
Nervous System Disorders 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.
Vascular Disorders Syncope
Respiratory, Thoracic and Dyspnoea
Mediastinal Disorders
General Disorders and Hypothermia
Administration Site
Conditions
Rare (>1/10,000)
Deletion of Psychiatric Disorders – Anxiety
And
Deletion of Nervous System Disorders – Convulsions
Addition of Cardiac Disorders Cardiac arrest, cardiac arrhythmias
Addition of General Disorder and Allergic reactions (anaphylactic reactions, angioneurotic
Administration Site oedema and urticaria)
Conditions
Addition of new text for footnote to asterisked comment – as follows
* These symptoms usually occur because of inadvertent intravascular injection, overdose or rapid absorption, see section 4.9
Section 4.8 addition and deletion of text
Current text:
Class-related adverse drug reactions:
Allergic reactions
Allergic reactions (in the most severe instances anaphylactic shock) to local anaesthetics of the amide type are rare.
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.
Acute systemic toxicity
Naropin may cause acute toxic effects following high doses or if very rapidly rising blood levels occur due to accidental intravascular injection or overdose. (See 4.9 Overdose.)
Total spinal block
Total spinal block may occur if an epidural dose is inadvertently administered intrathecally, or if a too large intrathecal dose is administered.
New text
Class-related adverse drug 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
Section 4.9
Addition and deletion of text
Current text
Symptoms:
Acute systemic toxicity
Accidental intravascular injections of local anaesthetics may cause immediate toxic effects. In the event of overdose, peak plasma concentrations may not be reached for one to two hours, depending on the site of the injection, and signs of toxicity may thus be delayed. Systemic toxic reactions may involve the central nervous system and the cardiovascular system.
New text
Symptoms:
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 drug, both quantitatively and qualitatively.
Accidental intravascular injections of local anaesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions. In the event of overdose, peak plasma concentrations may not be reached for one to two hours, depending on the site of the injection, and signs of toxicity may thus be delayed.
Section 5.1
Addition of new text after words Pharmacotherapeutic group “Anaesthetics, local, Amides”
Section 6.3
Addition of new text after the words “3 years” …
Shelf life after first opening:
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2–8°C.
Section 6.4
Addition of new text after the words “Do not freeze” …
For storage after opening, see section 6.3.
Section 10
New revision date of text
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