Ropivacaine Cabi 2 mg/ml 100 ml, 5 pcs.

A long-acting local anesthetic of the amide type, which is a pure enantiomer. It has both anesthetic and analgesic effect. By reversibly blocking potential-dependent Na+-channels it prevents generation of impulses in the endings of sensitive nerves and conduction of impulses along the nerve fibers.

Indications

At concentrations of 7.5 mg/1 ml and 10 mg/1 ml, Ropivacaine Cabi is used v adults and children over 12 years of age for the following indications:

Anesthesia in surgical procedures:

• epidural blockade in surgical procedures, including cesarean section;
• blockade of major nerves and nerve plexuses;
• blockade of individual nerves and infiltration anesthesia.

Intraarticular injection in knee arthroscopy.

At a concentration of 2 mg/1 ml, Ropivacaine Kabi is used for the following indications:

Capitation of acute pain syndrome in adults and children over 12 years of age.

• prolonged epidural infusion or intermittent bolus administration, such as for postoperative pain or labor pain;
• extended peripheral nerve block by infusion or bolus injections (for postoperative pain).

Acute pain management in children from 1 to 12 years (inclusive):

Single and prolonged peripheral nerve blockade.

In newborns and children under 12 years of age (inclusive);

• caudal epidural block;
• extended epidural infusion.

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Active ingredient

Ropivacaine

How to take, the dosage

The drug is used for perineural administration (spinal and conduction anesthesia).

Ropivacaine Kabi should only be administered by or under the supervision of professionals with sufficient experience in local anesthesia and with resuscitation equipment and medications available.

Adults and children over 12 years of age

In general, higher doses and more concentrated solutions of the drug are required for anesthesia in surgical procedures than are used for anesthetic purposes. For analgesia (e.g., epidural administration to suppress acute pain), lower concentrations and doses are recommended and a dose of 2 mg/1 ml is usually recommended. For intraarticular administration, a dose of 7.5 mg/1 ml is recommended. Ropivacaine Kabi 10 mg/1 mL is recommended for epidural anesthesia when complete motor blockade is necessary for surgery.

The following tables are a guide to dosage selection for the more commonly used blockades. A minimum dosage sufficient to form an effective blockade should be used. The experience of the clinical specialist and knowledge of the patient’s physical condition are important in deciding the dosage.

Table 1. Dosage recommendations for Ropivacaine Cabi for adults and children over 12 years of age

The dosages listed in Table 1 are considered sufficient for a successful blockade and should serve as a guide for use in adult patients, as there are individual variations in the timing and duration of the block. The values in the “Dose” column represent the expected range of averaged doses needed.

Ropivacaine Kabi dosing recommendations for adults and children over 12 years of age:

* The dosage for conduction anesthesia should be specified according to the site of application and the patient’s condition. Lumbar and supraclavicular brachial plexus blocks may result in a higher incidence of adverse reactions regardless of the local anesthetic used.

** Cases of chondrolysis have been reported with postoperative prolonged intra-articular infusion of local anesthetics. Ropivacaine Kabi should not be used for prolonged intra-articular administration.

*** If Roprivacaine Kabi has additionally been used for other types of anesthesia, the maximum dose should not exceed 225 mg.

¹ – Stepwise dosing should be used, with a starting dose of approximately 100 mg (97.55 mg=13 ml, 105 mg=14 ml) and administered within 3-5 minutes. Two additional doses, totaling an additional 50 mg, can be administered as needed.

² – N/A = not valid.

The standard guidelines should be used to familiarize yourself with the factors affecting the method of performing individual blockades and the requirements for specific patient groups.

In order to prevent the anesthetic from entering the vascular stream, aspiration testing should always be performed prior to and during the administration of the drug. If a large dose of the drug must be administered, a test dose of 3-5 ml of lidocaine with epinephrine is recommended. Accidental intravascular injection is recognized by a temporary increase in HR, and accidental intrathecal injection by signs of spinal block. If toxic symptoms occur, the drug administration should be stopped immediately.

Aspiration should be performed prior to and during administration of the main dose, which should be administered slowly or in increments of 25-50 mg/min, while carefully observing the patient’s vital functions and maintaining verbal contact with the patient.

The single infusion of Ropivacaine Cabi for surgical epidural block in doses up to 250 mg is generally well tolerated by patients.

In brachial plexus blockade with 40 ml of Ropivacaine Kabi 7.5 mg/1 ml, maximum plasma concentrations of ropivacaine in some patients may reach a value characterized by mild CNS toxicity symptoms. Therefore, the use of a dose higher than 40 ml of Ropivacaine Kabi 7.5 mg/1 ml (300 mg ropivacaine) is not recommended.

When using prolonged blockade either by continuous infusion or by repeated bolus administration, the risks of reaching toxic plasma concentrations or of local nerve damage must be taken into account. Ropnvacaine infusion for 24 hours at a dose of up to 800 mg total for surgical procedures and for postoperative pain relief, as well as extended epidural infusion after surgery at up to 28 mg/h for 72 hours is well tolerated by adult patients.

The following method is recommended for postoperative pain management: if an epidural catheter was not inserted during surgery, an epidural block with a bolus injection of Ropivacaine Kabi 7.5 mg/1 ml is performed after insertion. Analgesia is supported by an infusion of Ropivacaine Kabi 2 mg/1 ml. In most cases for moderate to severe postoperative pain, infusion at a rate of 6-14 ml/h (12-28 mg/h) provides adequate analgesia with minimal non-progressive motor blockade (with this technique, there was a significant reduction in the need for opioid analgesics). For postoperative analgesia, Ropivacaine Kabi 2 mg/1 ml can be administered continuously as an epidural infusion for 72 h without fentanyl or in combination with it (1-4 µg/ml). Ropivacaine Kabi 2 mg/1 mL (6-14 mL/hr) provided adequate analgesia in most patients.

The combination of Ropivacaine Kabi and fentanyl resulted in improved analgesia, while causing side effects common to narcotic analgesics.

The use of Ropivacaine Kabi concentrations greater than 7.5 mg/1 ml in cesarean sections has not been studied.

Renal impairment

In general, no change in dose is necessary when administering a single dose or short-term therapy in patients with impaired renal function.

Hepatic impairment

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

Patients with hypovolemia

Patients with hypovolemia may develop acute and severe hypotension during epidural anesthesia for any reason, regardless of the use of local anesthetic.

Table 2. Dosing recommendations for Ropivacaine Kabi for children 0 to 12 years old

^a – Smaller doses from the suggested dosing interval are recommended for thoracic and epidural blocks, whereas larger doses are recommended for lumbar and caudal epidural blocks.

^b – Recommended for lumbar epidural blockades. A lower bolus dose in the case of thoracic level analgesia is warranted.

The dosages in Table 2 should be considered guidelines for the use of the drug in pediatric practice. At the same time, there is individual variability in the rate at which the block develops and its duration. In overweight children, a gradual reduction of the drug dose is often required, and the patient’s ideal body weight should be considered as the basis. For factors affecting specific block techniques and individual patient requirements, the data given in the standard guidelines should be considered. The volume for a single caudal block and the volume for epidural bolus doses should not exceed 25 ml in any patient.

Before and during injection, careful aspiration is recommended to prevent intravascular injection. The patient’s vital functions should be closely monitored during the administration of the drug. In case of toxic symptoms, the infusion should be stopped immediately. A single caudal epidural injection of ropivacaine at a dose of 2 mg/1 ml (at the rate of 2 mg/kg, solution volume 1 ml/kg) forms adequate postoperative analgesia below T_1/2 in most patients.

Children over 4 years of age tolerate doses of 3 mg/kg well. The amount of epidural solution administered at the caudal level can be varied to achieve different prevalence of sensory block, as described in specialized guidelines.

Whatever the type of anesthesia, bolus administration of the calculated dose is recommended.

The use of the drug in concentrations higher than 5 mg/1 ml as well as intrathecal administration of Ropivacaine Kabi in children has not been studied.

The use of ropivacaine has not been studied in preterm infants regardless of the route of administration.

Interaction

This medicinal product should not be mixed with other medicinal products.

The concomitant use of Ropivacaine Cabi with local anesthetics, drugs structurally similar to local amide anesthetics or drugs depressing the central nervous system (CNS) may increase the toxic effects of the drugs.

Patients taking class III antiarrhythmic drugs (e.g., amiodarone) should be under constant medical supervision and ECG monitoring, as cardiovascular side effects may occur.

In alkaline solutions, ropivacaine hydrochloride may precipitate because it is weakly soluble at pH >6.0). In vivo, concomitant use of ketoconazole, a potent selective inhibitor of CYP3A4 isoenzyme, decreased plasma clearance of ropivacaine hydrochloride by 15%. However, inhibition of this isoenzyme is unlikely to be clinically significant.

In vitro ropivacaine hydrochloride is a competitive inhibitor of CYP2D6 isoenzyme, while inhibition of this isoenzyme is not achieved at the plasma concentrations of the drug used in practice.

Special Instructions

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Contraindications

• hypersensitivity to the active ingredient, any of the excipients or other local anesthetics of the amide type;
• also the general contraindications for each specific type of anesthesia should be considered, regardless of the anesthetic used;
• The drug Ropivacaine Cabi is contraindicated for intravenous regional “large” blockade anesthesia in patients with hypovolemia and paracervical anesthesia in obstetrics.

With caution

Elderly patients, patients in a weakened state or patients with severe comorbidities, including Grade II and III intracardiac conduction blockages (sinoatrial, atrioventricular, intraventricular), advanced liver disease, severe hepatic failure, severe chronic renal failure, acute porphyria, during therapy of hypovolemia, weakened patients, elderly, childhood, pregnancy and during lactation.

The use of regional anesthesia is preferable for these groups of patients. When performing “large” blocks, in order to reduce the risk of severe adverse events, it is recommended to stabilize the patient’s condition beforehand and to adjust the anesthetic dose.

Caution should be exercised when injecting local anesthetics into the head and neck region because of the possible increased frequency of serious adverse events.

Patients on a sodium-restricted diet should consider the sodium content of the drug.

Side effects

Adverse reactions to Ropivacaine Kabi are similar to those to other amide-type local anesthetics. Adverse reactions must be distinguished from physiological effects of the block itself, such as hypotension and bradycardia during subdural anesthesia, or effects associated with the technique of drug administration (e.g., spinal hematoma, local nerve damage, headache after subdural puncture, meningitis and epidural abscess).

Side effects common to local anesthetics

Central and peripheral nervous system disorders

Neuropathy and spinal cord dysfunction (anterior spinal artery syndrome, arachnoiditis, cauda equina syndrome) are possible, usually related to the technique of regional anesthesia rather than the action of the drug.

The accidental intrathecal administration of a dose in excess of the recommended dose may result in complete spinal block. Serious complications are possible with systemic overdose and unintentional intravascular administration of the drug (see section “Overdose”).

Acute systemic toxicity

Ropivacaine Kabi may cause acute systemic toxic reactions if high doses are used or if its blood concentration rises rapidly if the drug is inadvertently administered intravascularly or in overdose (see “Pharmacological properties” and “Overdose”).

The most frequently reported side effects of the drug

A variety of side effects have been reported, with the vast majority not related to the anesthetic agent used but to the regional anesthetic technique.

The most frequently reported adverse effects (>1%) were the following, which were considered to be clinically significant regardless of whether a causal relationship with anesthetic use was established: decreased BP*, nausea, bradycardia, vomiting, paresthesia, increased body temperature, headache, urinary retention, dizziness, chills, increased BP, tachycardia, hypoesthesia, anxiety.

The incidence of adverse effects is as follows: Very common – >1/10; common – >1/100 to <1/10; infrequent – >1/1000 to <1/100; rare – >1/10 000 to <1/1 000; very rare – <1/10 000; unknown – cannot be determined based on available data.

Nervous system disorders: frequent – headache, paresthesia, dizziness; infrequent – anxiety, symptoms of CNS toxicity (seizures, grand convulsive seizures, peroral paresthesia, tongue numbness, hyperacusis, tinnitus, visual disturbances, dysarthria, muscle twitches, tremor)*, hypoesthesia.

Chronic disorders: very common – decreased BP (hypotension); common – bradycardia, tachycardia, increased BP; infrequent – syncope; rare – cardiac arrest, arrhythmia.

Disorders of the respiratory system, thorax and mediastinum: infrequent – dyspnea, difficulty in breathing.

Gastrointestinal disorders: very common – nausea; common – vomiting.

River and urinary tract disorders: frequently – urinary retention.

General disorders and disorders with administration: frequently – back pain, hyperthermia, chills; infrequently – hypothermia; rarely – allergic reactions (anaphylactic reactions. angioedema and urticaria).

* These symptoms are usually associated with accidental intravascular administration, overdose, or rapid absorption.

^a – Hypotension in children is common (>1/100).

^b – Vomiting in children is very common (>1/10).

Overdose

Acute systemic toxicity

Inadvertent intravascular administration during plexus blocks or other peripheral blockages has resulted in cases of seizures.

If an intrathecal epidural dose of anesthetic is inappropriately administered, a complete spinal block may occur.

The accidental intravascular administration of anesthetic may cause an immediate toxic reaction.

In case of overdose during regional anesthesia, symptoms of a systemic toxic reaction appear delayed 15-60 minutes after injection due to a slow increase in plasma concentration of the local anesthetic.

Systemic toxicity is primarily manifested by symptoms of the central nervous system (CNS) and cardiovascular system (CVS). These reactions are caused by high concentrations of the local anesthetic in the blood, which may occur due to (accidental) intravascular administration, overdose or exceptionally high adsorption from highly vascularized areas.

CNS reactions are similar for all amide-type local anesthetics, whereas cardiovascular reactions are more dependent on the injected drug and its dose.

Central nervous system

The central nervous system manifestations of systemic toxicity develop gradually: first there are visual disturbances, numbness around the mouth, tongue numbness, hyperacusis, tinnitus, dizziness. Dysarthria, tremors and muscle twitching are more serious manifestations of systemic toxicity and may precede the appearance of generalized seizures (these signs should not be mistaken for the patient’s neurotic behavior). With progression of intoxication there may be loss of consciousness, seizures lasting from several seconds to several minutes, accompanied by respiratory disorders, rapid development of hypoxia and hypercapnia due to increased muscle activity and inadequate ventilation. In severe cases, respiratory arrest may even occur. Arising acidosis, hyperkalemia, hypocalcemia increase toxic effects of anesthetic.

Thereafter, due to redistribution of the anesthetic from the CNS and its subsequent metabolism and excretion, there is a fairly rapid recovery of function, unless a large dose of the drug was administered.

Cardiovascular system

Disorders of the cardiovascular system are signs of more serious complications. Decreased BP, bradycardia, arrhythmias, and in some cases even cardiac arrest can occur due to high systemic concentrations of local anesthetics. In rare cases, cardiac arrest is not accompanied by preceding CNS symptoms. In studies on volunteers, intravenous infusion of ropivacaine resulted in inhibition of conduction and cardiac contractility.

The cardiovascular symptoms are usually preceded by CNS toxicity that may not be seen if the patient is under sedation (benzodiazepines or barbiturates) or general anesthesia.

In children, early signs of systemic toxicity of local anesthetics may be more difficult to detect due to difficulties in describing symptoms in children or when regional anesthesia is combined with general anesthesia.

The treatment of acute toxicity

In case of the first signs of acute systemic toxicity, the drug should be stopped immediately.

In case of convulsions and CNS depression symptoms, the patient requires adequate treatment to maintain oxygenation, arrest convulsions, maintain cardiovascular activity. Oxygenation with oxygen should be provided, and if necessary, transfer to artificial lung ventilation. If seizures do not stop after 15-20 seconds, anticonvulsants should be used: sodium thiopental 1-3 mg/kg IV (provides rapid relief of seizures) or diazepam 0.1 mg/kg IV (action is slower compared to that of sodium thiopental). Suxamethonium 1 mg/kg quickly stops seizures, but intubation and ventilatory support are required.

In case of depressed cardiovascular activity (decreased BP, bradycardia) intravenous injection of 5-10 mg of ephedrine is necessary, repeat the injection after 2-3 minutes if necessary. If circulatory failure or cardiac arrest develops, standard resuscitation measures should be started immediately. It is vital to maintain optimal oxygenation, ventilation and blood circulation, and to correct acidosis. Longer resuscitation interventions may be necessary in cardiac arrest.

In therapy of systemic toxicity in children, doses should be adjusted according to the patient’s age and body weight.