Ropivacaine Kabi (Solution) Instructions for Use

ATC Code

N01BB09 (Ropivacaine)

Active Substance

Ropivacaine

Clinical-Pharmacological Group

Local anesthetic

Pharmacotherapeutic Group

Local anesthetic agent

Pharmacological Action

A long-acting amide-type local anesthetic, which is a pure enantiomer. It has both anesthetic and analgesic effects.

By reversibly blocking voltage-gated Na⁺ channels, it prevents the generation of impulses in the endings of sensory nerves and the conduction of impulses along nerve fibers.

High concentrations of the drug are used for local anesthesia during surgical interventions. Entering the systemic circulation in low concentrations, it can cause a sensory block (analgesia) with minimal and non-progressive motor block; entering in excessive amounts, it has a depressant effect on the CNS and myocardium (reduces its excitability, automaticity and conductivity). Epinephrine has practically no effect on the duration and intensity of the blockade caused by ropivacaine.

Signs of CNS toxicity precede signs of cardiovascular system toxicity, as they are observed at lower plasma concentrations of the drug.

Ropivacaine has a wide therapeutic range (the range between doses that have therapeutic and toxic effects). In vivo animal studies have shown that Ropivacaine has less toxic effect on the myocardium compared to bupivacaine.

Indirect cardiovascular effects (arterial hypotension, bradycardia) may occur after epidural administration of ropivacaine and are due to the resulting sympathetic blockade.

The onset and duration of anesthesia with Ropivacaine Kabi depend on the concentration and site of administration of the drug.

Pharmacokinetics

The concentration of ropivacaine in plasma depends on the dose, route of administration and the degree of vascularization of the injection area.

Pharmacokinetics is linear, C_max is proportional to the administered dose. After epidural administration, Ropivacaine is completely absorbed into the blood.

Absorption is biphasic, T_1/2 for each phase is 14 min and 4 h, respectively. The slowdown in the elimination of ropivacaine is determined by slow absorption, which explains the longer T_1/2 after epidural administration compared to IV administration.

The total plasma clearance of ropivacaine is 440 ml/min, the plasma clearance of the unbound substance is 8 L/min, renal clearance is 1 ml/min, V_d at steady state is 47 L, the hepatic extraction index is about 0.4, T_1/2 is 1.8 h.

Ropivacaine is intensively bound to plasma proteins (mainly to alpha1-acid glycoproteins), the unbound fraction of ropivacaine is about 6%.

Prolonged epidural administration of ropivacaine after surgical operations leads to an increase in the plasma concentration of the drug, which is due to an increase in the concentration of acid glycoproteins in the blood, while the concentration of the unbound, pharmacologically active form of ropivacaine in plasma changes to a much lesser extent than the total concentration of ropivacaine.

Ropivacaine penetrates the placental barrier well with rapid achievement of equilibrium in the unbound fraction.

Binding to plasma proteins in the fetus is less than in the mother, which leads to lower concentrations of the drug in the fetal plasma compared to the total concentration of the drug in the maternal plasma.

Ropivacaine is actively metabolized in the body, mainly by aromatic hydroxylation.

The main metabolites are: 3-hydroxyropivacaine, 4-hydroxyropivacaine, N-dealkylated metabolites and 4-hydroxydealkylated Ropivacaine. 3-hydroxyropivacaine (conjugated and unconjugated) is detected in plasma. 3-hydroxy- and 4-hydroxyropivacaine have a weaker local anesthetic effect compared to ropivacaine.

After IV administration, 86% of ropivacaine is excreted in the urine (only 1% unchanged). About 37% of 3-hydroxyropivacaine, the main metabolite of ropivacaine, is excreted in the urine (mainly in conjugated form).

1-3% of ropivacaine is excreted in the urine as metabolites: 4-hydroxyropivacaine, N-dealkylated metabolites and 4-hydroxydealkylated ropivacaine. There are no data on the racemization of ropivacaine in vivo.

Indications

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

Anesthesia for surgical interventions

• Epidural blockade for surgical interventions, including caesarean section;
• Blockade of large nerves and nerve plexuses;
• Blockade of individual nerves and infiltration anesthesia.

Intra-articular injection for knee arthroscopy.

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

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

• Prolonged epidural infusion or intermittent bolus administration, for example, to relieve postoperative pain or labor analgesia;
• Blockade of individual nerves and infiltration anesthesia;
• Prolonged peripheral nerve blockade by infusion or bolus injections (for postoperative pain).

Relief of acute pain syndrome in children from 1 year to 12 years (inclusive)

• Single and prolonged peripheral nerve blockade.

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

• Caudal epidural blockade;
• Prolonged epidural infusion.

ICD codes

Dosage Regimen

Solution

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

Ropivacaine Kabi should only be administered by specialists with sufficient experience in local anesthesia or under their supervision, with equipment and drugs for resuscitation available.

Adults and children over 12 years of age

In general, for anesthesia during surgical interventions, higher doses and more concentrated solutions of the drug are required than when using an anesthetic for analgesia. For analgesia (for example, epidural administration for acute pain relief), lower concentrations and doses are recommended and a dose of 2 mg/1 ml is usually recommended. For intra-articular 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 for dosing the more commonly used blocks. The minimum dosage sufficient to produce an effective block should be used. When deciding on the dose, the clinical specialist’s experience and knowledge of the patient’s physical condition are important.

Table 1. Dosing recommendations for the drug Ropivacaine Kabi for adults and children over 12 years of age

The dosages given in Table 1 are considered sufficient to perform a successful block and should serve as a guide for use in adult patients, as there are individual variations in the time of block onset and its duration. The values in the “Dose” column reflect the expected range of average required doses.

Dosing recommendations for the drug Ropivacaine Kabi 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. Interscalene and supraclavicular blocks of the brachial plexus may lead to a higher frequency 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 long-term intra-articular administration.

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

¹ – Stepwise dosing should be used, an initial dose of about 100 mg (97.55 mg=13 ml, 105 mg=14 ml) and administered over 3-5 min. Two additional doses, totaling an additional 50 mg, may be administered if necessary.

²– N/A = not applicable.

Standard guidelines should be used to familiarize with the factors influencing the method of performing individual blocks and the requirements for specific patient groups.

To prevent the anesthetic from entering the vascular bed, an aspiration test must be performed before and during the administration of the drug. If a large dose of the drug is required, it is recommended to administer a test dose of 3-5 ml of lidocaine with epinephrine. Accidental intravascular administration is recognized by a temporary increase in heart rate, and accidental intrathecal administration is recognized by signs of spinal block. If toxic symptoms occur, the administration of the drug should be stopped immediately.

Aspiration should be performed before and during the administration of the main dose, which must be administered slowly or in steps, at a rate of 25-50 mg/min, carefully monitoring the patient’s vital functions and maintaining verbal contact with him/her.

A single administration of the drug Ropivacaine Kabi for epidural blockade for surgical intervention in a dose of up to 250 mg is usually well tolerated by patients.

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

When using prolonged blockade, either by continuous infusion or by repeated bolus administration, the risks of reaching a toxic plasma concentration or the occurrence of local nerve damage should be taken into account. Administration of ropivacaine over 24 hours in a total dose of up to 800 mg for surgical interventions and for postoperative analgesia, as well as prolonged epidural infusion after surgery at a rate of up to 28 mg/h for 72 hours, is well tolerated by adult patients.

The following method is recommended for the relief of postoperative pain: if an epidural catheter was not installed during the operation, after its installation, an epidural block is performed with a bolus injection of Ropivacaine Kabi 7.5 mg/1 ml. Analgesia is maintained by infusion of Ropivacaine Kabi 2 mg/1 ml. In most cases, for the relief of 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 (when using this technique, a significant reduction in the need for opioid analgesics was observed). For postoperative analgesia, Ropivacaine Kabi 2 mg/1 ml can be administered continuously as an epidural infusion for 72 hours without fentanyl or in combination with it (1-4 mcg/ml). When using the drug Ropivacaine Kabi 2 mg/1 ml (6-14 ml/h), adequate pain relief was provided in most patients.

The combination of the drug Ropivacaine Kabi and fentanyl led to improved pain relief, while causing side effects inherent in narcotic analgesics.

The use of the drug Ropivacaine Kabi in a concentration above 7.5 mg/1 ml for caesarean section has not been studied.

Renal failure

As a rule, when administering a single dose or short-term therapy to patients with impaired renal function, no dose adjustment is required.

Hepatic insufficiency

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 suffering from hypovolemia

In patients suffering from hypovolemia, acute and severe hypotension may develop during epidural anesthesia, regardless of the use of a local anesthetic.

Table 2. Dosing recommendations for the drug Ropivacaine Kabi for children from 0 to 12 years of age

^a – Lower doses from the proposed dosing range are recommended for thoracic and epidural blocks, while higher doses are for lumbar and caudal epidural blocks.

^b – Recommended for lumbar epidural blocks. A reduction in the bolus dose is justified for analgesia at the thoracic level.

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

Careful aspiration is recommended before and during injection to prevent intravascular injection. During drug administration, the patient’s vital functions must be carefully monitored. If toxic symptoms occur, 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) provides adequate postoperative analgesia below the T_1/2 level in most patients.

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

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

The use of the drug in a concentration above 5 mg/1 ml, as well as intrathecal use of the drug Ropivacaine Kabi in children has not been studied.

Regardless of the route of administration, the use of ropivacaine has not been studied in premature infants.

Instructions for use of the solution

The solution does not contain preservatives and is intended for single use only.

It must be used immediately after opening the ampoule or “Friflex^®” bag; any unused residue of the drug must be destroyed.

Before use, the medicinal product must be carefully inspected.

The injection solution is only suitable if it is transparent, visible mechanical particles are absent, and the container is not damaged.

Any amount of solution remaining in the container after use must be destroyed. An unopened container with the solution must not be autoclaved. The unopened blister pack ensures the sterility of the external surface of the container and is preferred for use in conditions requiring sterility.

Adverse Reactions

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

Side effects inherent to local anesthetics

Central and peripheral nervous system

Neuropathy and impaired spinal cord function (anterior spinal artery syndrome, arachnoiditis, cauda equina syndrome) are possible, usually associated with the technique of regional anesthesia, not with the drug’s action.

Accidental intrathecal administration of a dose exceeding the recommended one may result in total spinal block. Serious complications are possible with systemic overdose and unintentional intravascular administration of the drug (see the “Overdose” section).

Acute systemic toxicity

Ropivacaine Kabi can cause acute systemic toxic reactions when high doses are used or when its blood concentration rapidly increases due to accidental intravascular administration or overdose (see the “Pharmacological properties” and “Overdose” sections).

Most frequently occurring side effects

Various side effects of the drug have been reported, the vast majority of which were not associated with the effect of the anesthetic used, but with the technique of regional anesthesia.

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

The frequency of adverse effects is presented as follows: very common – >1/10; common – >1/100 to <1/10; uncommon - >1/1000 to <1/100; rare - >1/10,000 to <1/1,000; very rare - <1/10,000; unknown - cannot be estimated from the available data.

Nervous system disorders: common – headache, paresthesia, dizziness; uncommon – anxiety, symptoms of toxic effects on the CNS (convulsions, grand mal seizures, perioral paresthesias, tongue numbness, hyperacusis, tinnitus, visual disturbances, dysarthria, muscle twitching, tremor)*, hypoesthesia.

Cardiac disorders: very common – decreased BP (hypotension); common – bradycardia, tachycardia, increased BP; uncommon – syncope; rare – cardiac arrest, arrhythmias.

Respiratory, thoracic and mediastinal disorders: uncommon – dyspnea, difficult breathing.

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

Renal and urinary disorders: common – urinary retention.

General disorders and administration site conditions: common – back pain, hyperthermia, chills; uncommon – hypothermia; rare – 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).

Contraindications

• Hypersensitivity to the active substance, to any of the excipients or to other amide-type local anesthetics;
• General contraindications for each specific type of anesthesia, regardless of the anesthetic used, must also be considered;
• The drug Ropivacaine Kabi is contraindicated for IV regional anesthesia “Bier’s block” in patients with hypovolemia and for paracervical block in obstetrics.

With caution

Elderly patients, debilitated patients, or patients with severe comorbidities, including grade II and III cardiac conduction blocks (sinoatrial, atrioventricular, intraventricular), progressive liver disease, severe hepatic insufficiency, severe chronic renal failure, acute porphyria, during hypovolemia therapy, debilitated patients, elderly age, children, pregnancy and lactation period.

For these patient groups, regional anesthesia is preferred. When performing “major” blocks to reduce the risk of severe adverse events, it is recommended to stabilize the patient’s condition beforehand and adjust the anesthetic dose.

Caution should be exercised when injecting local anesthetics in the head and neck area, due to a possible increased frequency of serious adverse events.

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

Use in Pregnancy and Lactation

No direct or indirect adverse effects on the course of pregnancy, embryonic/fetal development, childbirth, and postnatal development have been identified. Ropivacaine Kabi can be used during pregnancy only if the potential benefit justifies the possible risk to the fetus.

Currently, there are no clinical data regarding the excretion of ropivacaine in breast milk in nursing mothers. Based on experimental data, the dose of the drug received by the newborn is approximately 4% of the dose administered to the mother (i.e., the total dose of ropivacaine affecting the child during breastfeeding is significantly less than the dose that could be received by the newborn when the anesthetic is administered to the mother during childbirth). If it is necessary to use the drug during breastfeeding, the ratio of potential benefit for the mother and possible risk for the infant should be considered.

Use in Hepatic Impairment

Ropivacaine is metabolized in the liver and, therefore, should be used with caution in patients with serious liver diseases.

Use in Renal Impairment

As a rule, when administering a single dose or short-term therapy to patients with impaired renal function, dose adjustment is not required.

Use the drug with caution in patients with severe chronic renal failure.

Pediatric Use

Recommended doses for newborns are based on limited clinical data. When using the drug Ropivacaine Kabi in newborns, monitoring for systemic toxicity (monitoring for signs of CNS toxicity, ECG, monitoring blood oxygenation) and local neurotoxicity is necessary, which should continue after the infusion is completed due to the slow elimination of the drug in newborns.

Children over 4 years of age tolerate doses of 3 mg/kg well. The use of the drug in concentrations above 5 mg/1 ml, as well as intrathecal use of the drug Ropivacaine Kabi in children, has not been studied.

Geriatric Use

Use the drug with caution in elderly patients.

Special Precautions

Anesthesia should be performed by experienced specialists in specially equipped rooms. Equipment and medications for resuscitation must be available. An intravenous catheter must be inserted in the patient before starting conduction blocks.

The specialist must be familiar with the precautions and have appropriate experience in diagnosing and treating possible side effects, systemic toxicity, and other complications, such as irreversible subarachnoid administration, which can cause significant spinal block with apnea and hypotension. Convulsions occur more often after brachial plexus block and epidural block. This is most likely the result of accidental intravascular injection or rapid absorption at the injection site. Blocks of major peripheral nerves can lead to the injection of a significant volume of local anesthetic into a highly vascularized area, often close to large vessels, where there may be an increased risk of intravascular injection and/or rapid systemic absorption, which can lead to high plasma concentrations of the drug. Some local anesthetic procedures, such as injections in the head and neck area, may be associated with an increased frequency of serious adverse reactions, regardless of the anesthetic used. Caution should be exercised to prevent injection into an inflamed area.

Elderly and debilitated patients, patients with grade II and III cardiac conduction blocks, patients with severe renal failure require special attention; however, such patients are often indicated for local anesthesia.

There are isolated reports of cardiac arrest with the use of ropivacaine for epidural anesthesia or peripheral nerve block, especially after accidental intravascular administration to elderly patients and patients suffering from concomitant heart disease.

In some cases, resuscitation may be difficult. In case of cardiac arrest, effective resuscitation may require a prolonged period.

Ropivacaine Kabi is metabolized in the liver and, therefore, should be used with caution in patients with liver disease: repeated doses may need to be reduced due to delayed elimination.

Usually, there is no need to adjust the dosage in patients with renal and hepatic insufficiency during single or short-term therapy. However, acidosis and decreased plasma protein concentrations, often observed in patients with chronic renal failure, may increase the risk of systemic intoxication.

Spinal anesthesia can lead to decreased BP and bradycardia. Administration of vasoconstrictor drugs or increasing the circulating blood volume can reduce the risk of such side effects.

Arterial hypotension should be corrected promptly by administering 5-10 mg of ephedrine; if necessary, the administration can be repeated. Patients taking class III antiarrhythmic drugs (e.g., amiodarone) should be under constant medical supervision and ECG monitoring, as cardiovascular side effects may occur.

Long-term use of ropivacaine should be avoided in patients concurrently taking strong inhibitors of the CYP1A2 isoenzyme, such as fluvoxamine and enoxacin.

Possible cross-hypersensitivity with other amide-type anesthetics should be taken into account – the type of local anesthetic should be considered.

Patients on a sodium-restricted diet should take into account the sodium content in the drug.

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

The effect of age is expressed in the development and maturity of liver function; clearance reaches its maximum value at the age of about 1-3 years. The T_1/2 of ropivacaine is 5-6 hours in newborns and children aged 1 month compared to 3 hours in older children.

Due to insufficient development of liver functions, systemic exposure to ropivacaine is higher in newborns, moderately higher in children from 1 to 6 months compared to older children.

Significant differences in ropivacaine plasma concentrations in newborns identified in clinical studies suggest an increased risk of systemic toxicity in this patient group, especially during prolonged epidural infusion.

Recommended doses for newborns are based on limited clinical data.

When using the drug Ropivacaine Kabi in newborns, monitoring for systemic toxicity (monitoring for signs of CNS toxicity, ECG, monitoring blood oxygenation) and local neurotoxicity is necessary, which should continue after the infusion is completed due to the slow elimination of the drug in newborns.

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

Ropivacaine Kabi injection solution may have porphyrinogenic properties and may be used in patients diagnosed with acute porphyria only if there is no safer alternative. In case of increased sensitivity in patients, necessary precautions must be taken.

Cases of chondrolysis have been reported with postoperative prolonged intra-articular infusion of local anesthetics. In most described cases, infusion was into the shoulder joint. A causal relationship with the anesthetic has not been established.

Ropivacaine should not be used for prolonged intra-articular infusion.

Information on the possible effect of the medicinal product for medical use on the ability to drive vehicles, machinery

It is necessary to refrain from potentially hazardous activities requiring increased attention and speed of psychomotor reactions, as motor functions, coordination of movements, and reaction speed are temporarily impaired.

Overdose

Acute systemic toxicity

Cases of seizures have been observed with accidental intravascular administration during nerve plexus blocks or other peripheral blocks. If an epidural dose of the anesthetic is incorrectly administered intrathecally, total spinal block may occur.

Accidental intravascular administration of the anesthetic can cause an immediate toxic reaction.

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

Systemic toxicity primarily manifests with symptoms from the CNS and cardiovascular system (CVS). These reactions are caused by high blood concentrations of the local anesthetic, which can occur due to (accidental) intravascular administration, overdose, or exceptionally high absorption from highly vascularized areas.

CNS reactions are similar for all amide-type local anesthetics, while cardiovascular system reactions depend more on the administered drug and its dose.

Central nervous system

Manifestations of systemic CNS toxicity develop gradually: first, visual disturbances, numbness around the mouth, tongue numbness, hyperacusis, ringing in the ears, dizziness appear. Dysarthria, tremor, and muscle twitching are more serious manifestations of systemic toxicity and may precede the onset of generalized convulsions (these signs should not be mistaken for neurotic patient behavior). With the progression of intoxication, loss of consciousness, seizure attacks lasting from several seconds to several minutes, accompanied by respiratory impairment, rapid development of hypoxia and hypercapnia due to increased muscle activity and inadequate ventilation may be observed. In severe cases, respiratory arrest may even occur. The resulting acidosis, hyperkalemia, and hypocalcemia enhance the toxic effects of the anesthetic.

Subsequently, due to the redistribution of the anesthetic from the CNS and its subsequent metabolism and excretion, a fairly rapid recovery of functions occurs, 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, arrhythmia, and, in some cases, even cardiac arrest can occur due to high systemic concentrations of local anesthetics. In rare cases, cardiac arrest is not preceded by CNS symptoms. In volunteer studies, IV infusion of ropivacaine led to depression of conduction and contractility of the heart muscle. Symptoms from the cardiovascular system are usually preceded by manifestations of CNS toxicity, which may go unnoticed if the patient is under the influence of sedatives (benzodiazepines or barbiturates) or under general anesthesia.

In children, early signs of systemic toxicity of local anesthetics are sometimes more difficult to detect due to difficulties children experience in describing symptoms, or in the case of regional anesthesia combined with general anesthesia.

Treatment of acute toxicity

At the first signs of acute systemic toxicity, administration of the drug should be stopped immediately.

If convulsions and symptoms of CNS depression appear, the patient requires adequate treatment aimed at maintaining oxygenation, stopping convulsions, and maintaining cardiovascular system activity. Oxygenation with oxygen should be ensured, and if necessary, transition to artificial ventilation of the lungs. If convulsions do not stop within 15-20 seconds, anticonvulsants should be used: sodium thiopental 1-3 mg/kg IV (provides rapid relief of convulsions) or diazepam 0.1 mg/kg IV (action develops slower compared to sodium thiopental). Succinylcholine 1 mg/kg rapidly stops convulsions, but its use requires intubation and artificial ventilation of the lungs.

In case of depression of cardiovascular system activity (decreased BP, bradycardia), IV administration of 5-10 mg of ephedrine is necessary; if necessary, repeat administration after 2-3 minutes. 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, as well as to correct acidosis. In case of cardiac arrest, prolonged resuscitation may be required.

When treating systemic toxicity in children, doses must be adjusted according to the patient’s age and body weight.

Drug Interactions

Concomitant use of the drug Ropivacaine Kabi with local anesthetics, drugs structurally similar to amide-type local anesthetics, or medicinal products that depress the CNS may enhance 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 vivo, with the concomitant use of fluvoxamine, a potent selective inhibitor of the CYP1A2 isoenzyme, the plasma clearance of ropivacaine hydrochloride decreased by 77%. Thus, strong inhibitors of the CYP1A2 isoenzyme, such as fluvoxamine and enoxacin, when used concomitantly with the drug Ropivacaine Kabi, may interact with ropivacaine hydrochloride. Long-term administration of ropivacaine hydrochloride should be avoided in patients receiving treatment with strong inhibitors of the CYP1A2 isoenzyme.

In vivo, with the simultaneous use of ketoconazole, a potent selective inhibitor of the CYP3A4 isoenzyme, the plasma clearance of ropivacaine hydrochloride decreased by 15%. However, the inhibition of this isoenzyme is unlikely to be clinically significant.

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

In alkaline solutions, ropivacaine hydrochloride may precipitate because it is poorly soluble at pH > 6.0.

The Ropivacaine Kabi solution in plastic infusion bags is chemically and physically compatible with the following medicinal products.

Despite the fact that the resulting mixtures retain chemical and physical stability for 30 days at a temperature not exceeding 30°C (86°F), based on microbiological purity data, the resulting solution mixtures should be used immediately after preparation.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F). Do not freeze!

Shelf Life

The shelf life of polypropylene ampoules is 3 years, for the “Friflex^®” container (bag) – 2 years.

Do not use the drug after the expiration date stated on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.