Ropivacaine Kabi solution for injection 5mg/ml 10ml, 5pcs

Pharmacological action

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

High concentrations of the drug are used for local anesthesia during surgical procedures. Getting into the systemic circulation in low concentrations, it can cause sensory block (analgesia) with minimal and non-progressive motor block, getting into excessive amounts, it has a depressing effect on the central nervous system (CNS) and myocardium (reduces its excitability, automatism and conductivity). Epinephrine has virtually no effect on the duration and intensity of the blockade caused by ropivacaine. Signs of toxicity from the central nervous system precede signs of toxicity from the cardiovascular system, since they are observed at lower concentrations of the drug in plasma. Ropivacaine has a wide therapeutic range (the range between therapeutic and toxic doses). In vivo animal studies have shown that ropivacaine has a lower toxic effect on the myocardium compared to bupivacaine. Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural use of ropivacaine and are due to the resulting sympathetic blockade.

The beginning and duration of anesthesia with Ropivacaine Kabi depend on the concentration and place of use of the drug.

Indications

At 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 during surgical procedures:

• epidural blockage for surgical procedures, including Caesarean section;
• blockage of major nerves and nerve plexuses;
• blockage of individual nerves and infiltration anesthesia.

Intra-articular injection for arthroscopy of the knee joint.

At 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 periodic bolus use, for example, to eliminate postoperative pain or analgesia of labor;
• blockage of individual nerves and infiltration anesthesia;
• extended blockage of peripheral nerves 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 blockage of peripheral nerves.

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

• caudal epidural block;
• prolonged epidural infusion.

Contraindications

• hypersensitivity to the Active ingredient, to any of the excipients or other local anesthetics of the amide type;
• it is also necessary to take into account general contraindications for each specific type of anesthesia, regardless of the anesthetic used;
• the drug Ropivacaine Kabi is contraindicated for intravenous regional anesthesia of “large” blockade in patients with hypovolemia and paracervical anesthesia in obstetrics.

With caution

Elderly patients, patients in a weakened state or patients with severe concomitant diseases, including grade II and III intracardiac conduction blockages (sinoatrial, atrioventricular, intraventricular), progressive liver diseases, severe hepatic insufficiency, severe chronic renal failure, acute porphyria, with hypovolemia therapy, weakened patients, the elderly, children, pregnancy and lactation.

For these groups of patients, the use of regional anesthesia is preferable. When performing “large” blockades in order to reduce the risk of severe adverse events, it is recommended to first stabilize the patient’s condition, as well as adjust the dose of anesthetic.

Caution should be exercised when injecting local anesthetics in the head and neck area, due to 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 reactions to other local anesthetics of the amide type. Adverse reactions should be distinguished from the physiological effects of the block itself, such as hypotension and bradycardia during subdural anesthesia, or effects related to the technique of drug use (for example, spinal hematoma, local nerve damage, headache after subdural puncture, meningitis and epidural abscess).

Side effects of local anesthetics

Central and peripheral nervous system disorders

Possible neuropathy and spinal cord dysfunction (anterior spinal artery syndrome, arachnoiditis, ponytail syndrome), usually associated with the technique of regional anesthesia, and not with the action of the drug.

Complete spinal block may occur as a result of accidental intrathecal use of a dose exceeding the recommended dose. Serious complications are possible with systemic overdose and unintentional intravascular use of the drug (see the section “Overdose”).

Acute systemic toxicity

Ropivacaine Kabi can cause acute systemic toxic reactions when used at high doses or with a rapid increase in its concentration in the blood with accidental intravascular use of the drug or its overdose (see the section “Pharmacological properties” and “Overdose”).

Most common side effects

Various side effects of the drug were reported, the vast majority of which were related not to the effect of the anesthetic used, but to the technique of regional anesthesia.

The most common side effects (>1%) were those that were considered clinically relevant, regardless of whether a causal relationship was established with the use of an anesthetic: decreased blood pressure*, nausea, bradycardia, vomiting, paresthesia, fever, headache, urinary retention, dizziness, chills, increased blood pressure, tachycardia, hyposthesia, anxiety.

The frequency of occurrence of undesirable effects is presented as follows:  very often – >1/10; often – > > 1/100 to >><1/10; infrequently – >1/1000 to <1/10; infrequently – ><1/100; rarely – >1/10 000 to <1/100; rarely – ><1/1 000; very rarely –

Nervous system disorders:  often-headache, paresthesia, dizziness; infrequently-anxiety, symptoms of toxic effects on the central nervous system (convulsions, large convulsive seizures, paresthesia in the perioral zone, tongue numbness, hyperacusis, tinnitus, visual disturbances, dysarthria, muscle twitching, tremor)*, hypesthesia.

Cardiac disorders:  very often-a decrease in blood pressure (hypotension); often-bradycardia, tachycardia, increased blood pressure; infrequently-fainting; rarely-cardiac arrest, arrhythmias.

Respiratory, thoracic and mediastinal disorders:  infrequently – shortness of breath, difficulty breathing.

Gastrointestinal disorders:  very often – nausea; often-vomiting.

Kidney and urinary tract disorders:  often-delayed urination.

General disorders and disorders when administered:  often – back pain, hyperthermia, chills; infrequently-hypothermia; rarely-allergic reactions (anaphylactic reactions. angioedema and urticaria).

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

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

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

Interaction

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

Concomitant use of Ropivacaine Kabi with local anesthetics, drugs structurally similar to local anesthetics of the amide type, or drugs that depress the central nervous system (CNS) may increase the toxic effects of the drugs.

Patients taking Class III antiarrhythmic drugs (for example, amiodarone) should be under constant medical supervision and ECG monitoring, as side effects from the cardiovascular system may occur.

In alkaline solutions of ropivacaine hydrochloride can precipitate, since it is slightly soluble at pH >6.0).

In vivo, plasma clearance of ropivacaine hydrochloride was reduced by 77% when fluvoxamine, a potent selective inhibitor of the CYP1A2 isoenzyme, was co-administered. Thus, strong inhibitors of the CYP1A2 isoenzyme, such as fluvoxamine and enoxacin, when co-administered with Ropivacaine Kabi, may interact with ropivacaine hydrochloride. Long-term use of ropivacaine hydrochloride should be avoided in patients receiving treatment with strong inhibitors of the CYP1A2 isoenzyme.

In vivo, plasma clearance of ropivacaine hydrochloride was reduced by 15% when ketoconazole, a potent selective inhibitor of the CYP3A4 isoenzyme, was co-administered. However, inhibition of this isoenzyme is unlikely to be clinically significant.

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

How to take, course of use and dosage

For perineural use (spinal and conduction anesthesia)

IV catheters should be installed before major blockages are performed.

Ropivacaine Kabi is administered slowly or by increasing sequential doses of the drug at a rate of 25-50 mg / min.

To prevent the anesthetic from entering the vessel, it is necessary to conduct an aspiration test before and during the use of the drug. Random intravascular injection is recognized by a temporary increase in heart rate.

The following table provides guidance on the dosage selection for intrathecal blockage, acute pain relief, and peripheral nerve blockage. A minimum dosage sufficient to form an effective blockade should be used. When deciding on a dose, the experience of a clinical specialist and knowledge of the patient’s physical condition are important.

Recommendations for dosage of Ropivacaine Kabi for adults and children over 12 years of age (see table 2)

Table 2

Recommendations for the dosage of Ropivacaine Kabi for children from 1 year to 12 years (see Table 3)

Table 3

The doses indicated in the table are considered sufficient to achieve reliable blockade and are indicative when using the drug in adults, since there is individual variability in the rate of block development and its duration.

For anesthesia during cesarean section, the intrathecal route of use of ropivacaine hydrochloride has not been studied.

There are individual differences in the beginning of the blockade and its duration.

The values in the Dose column reflect the estimated average range of required dosages. For information on the factors influencing the method of blockade and individual characteristics of patients, please refer to the standard manuals.

Due to the lack of sufficient clinical observations, it is not recommended to use Ropivacaine Kabi in children under 1 year of age.

Overdose

Acute systemic toxicity

Seizures have been reported with accidental intravascular use during nerve plexus blockades or other peripheral blockades.

If the epidural dose of an anesthetic is administered incorrectly intrathecally, a complete spinal block may occur.

Accidental intravascular injection of an anesthetic may cause an immediate toxic reaction.

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

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

Reactions from the central nervous system are similar for all local anesthetics of the amide type, while reactions from the cardiovascular system are more dependent on the drug administered and its dose.

Central nervous system

Manifestations of systemic toxicity from the central nervous system develop gradually: first there are visual disturbances, numbness around the mouth, numbness of the tongue, hyperacusis, ringing in the ears, dizziness. Dysarthria, tremor and muscle twitching are more serious manifestations of systemic toxicity and may precede the appearance of generalized seizures (these signs should not be taken as neurotic behavior of the patient). With the 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. The resulting acidosis, hyperkalemia, and hypocalcemia increase the toxic effects of the anesthetic.

Subsequently, due to the redistribution of the anesthetic from the central nervous system and its subsequent metabolism and excretion, a fairly rapid recovery of functions occurs, unless a large dose of the drug has been administered.

Cardiovascular system

Disorders of the cardiovascular system are signs of more serious complications. Low blood pressure, bradycardia, arrhythmia and, in some cases, even cardiac arrest may occur due to high systemic concentrations of local anesthetics. In rare cases, cardiac arrest is not accompanied by previous symptoms from the central nervous system. In studies on volunteers, intravenous infusion of ropivacaine resulted in inhibition of conduction and contractility of the heart muscle.

Symptoms from the cardiovascular system are usually preceded by manifestations of toxicity from the central nervous system, which may not be noticed if the patient is under sedation (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 the difficulties experienced by children in describing symptoms, or when regional anesthesia is used in combination with general anesthesia.

Treatment of acute toxicity

When the first signs of acute systemic toxicity appear, the drug should be discontinued immediately.

When seizures and symptoms of CNS depression appear, the patient needs adequate treatment, the purpose of which is to maintain oxygenation, stop seizures, and maintain the activity of the cardiovascular system. Oxygenation with oxygen should be provided, and if necessary, the transition to artificial ventilation of the lungs. If the convulsions do not stop after 15-20 seconds, anticonvulsants should be used: thiopental sodium 1-3 mg/kg iv (provides rapid relief of seizures) or diazepam 0.1 mg / kg IV (the effect develops more slowly compared to the effect of sodium thiopental). Suxamethonium 1 mg / kg quickly stops seizures, but its use requires intubation and artificial ventilation of the lungs.

If the activity of the cardiovascular system is inhibited (decreased blood pressure, bradycardia), intravenous use of 5-10 mg of ephedrine is necessary, if necessary, repeat the use after 2-3 minutes. If circulatory failure or cardiac arrest develops, standard resuscitation measures should be initiated immediately. It is vital to maintain optimal oxygenation, ventilation, and blood circulation, as well as correct acidosis. In case of cardiac arrest, longer resuscitation measures may be required.

When treating systemic toxicity in children, it is necessary to adjust the dose according to the patient’s age and body weight.

Special instructions

Anesthesia should be performed by experienced specialists in specially equipped rooms. It is mandatory to have equipment and medicines for resuscitation. An intravenous catheter should be inserted into the patient prior to conducting conduction blockages.

The specialist should be familiar with the precautions and have appropriate experience in the diagnosis and treatment of possible side effects, systemic toxicity, and other complications, such as irreversible subarachnoid use, which can cause severe spinal block with apnea and hypotension.

Seizures are more common after brachial plexus block and epidural block. Most likely, this may be the result of accidental intravascular use or rapid absorption at the injection site.

Performing peripheral nerve blockages may require injecting a large volume of local anesthetic into areas with a large number of vessels, often near large vessels, which increases the risk of intravascular use and / or rapid systemic absorption, which can lead to high plasma concentrations of the drug.

Some local anesthetic procedures, such as head and neck injections, may be associated with an increased frequency of serious adverse reactions, regardless of the anesthetic used.Care should be taken to prevent injection into the inflamed area.

Elderly and debilitated patients, patients with grade II and III intracardiac conduction block, and patients with severe renal insufficiency require special attention, but local anesthesia is often indicated for such patients.

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

In some cases, resuscitation may be difficult. When cardiac arrest occurs, effective resuscitation measures may take a long time.

Ropivacaine 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 with a single or short-term therapy. However, acidosis and decreased plasma protein concentrations, often seen in patients with chronic renal failure, may increase the risk of systemic intoxication.

Spinal anesthesia can lead to a decrease in blood pressure (BP) and bradycardia. The use of vasoconstrictor drugs or an increase in the volume of circulating blood can reduce the risk of such side effects. Arterial hypotension should be corrected in a timely manner by use of 5-10 mg of ephedrine, if necessary, the use can be repeated.

Patients taking Class III antiarrhythmic drugs (for example, amiodarone) should be under constant medical supervision and ECG monitoring, as side effects from the cardiovascular system may occur. Long-term use of ropivacaine should be avoided in patients receiving concomitant treatment with strong CYP1A2 inhibitors, such as fluvoxamine and enoxacin.

Possible cross-hypersensitivity with other amide-type anaesthetics should be taken into account – the type of local anaesthetic should be taken into account.

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

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

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

Indication, if necessary, of special precautions when disposing of unused medicinal products

The unused solution must be disposed of in accordance with the current requirements for drug disposal adopted in this hospital.

Influence on the ability to drive vehicles and mechanisms:

It is necessary to refrain from potentially dangerous activities that require increased attention and speed of psychomotor reactions, as motor functions, coordination of movements and reaction speed are temporarily disrupted.

Storage conditions

Store at a temperature not exceeding 25 °C.

Do not freeze it.

Keep out of reach of children.

Expiration date

Polypropylene ampoules – 3 years.

Do not use the product after the expiration date indicated on the package.

Active ingredient

Ropivacaine

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection