Ropivacaine - instructions for use, dose, side effects, contraindications

Excipients: sodium chloride - 8.6 mg, sodium hydroxide solution of 2 M and / or hydrochloric acid solution of 2 M to adjust the pH to 4.0 - 6.0, water for injection - up to 1.0 ml.

Dosage: 5 mg / ml

Composition per ml:

Active substance: ropivacaine hydrochloride monohydrate in terms of ropivacaine hydrochloride 5.0 mg;

Excipients: sodium chloride - 8.0 mg, sodium hydroxide solution of 2 M and / or hydrochloric acid solution of 2 M to adjust the pH to 4.0 - 6.0, water for injection - up to 1.0 ml.

Dosage: 7.5 mg / ml

Composition per ml:

Active substance: ropivacaine hydrochloride monohydrate in terms of ropivacaine hydrochloride - 7.5 mg;

Excipients: sodium chloride - 7.5 mg, sodium hydroxide solution of 2 M and / or hydrochloric acid solution of 2 M to adjust the pH to 4.0 - 6.0, water for injection - up to 1.0 ml.

Dosage: 10 mg / ml

Composition per ml:

Active substance: ropivacaine hydrochloride monohydrate in terms of ropivacaine hydrochloride - 10.0 mg;

Excipients: sodium chloride - 7.1 mg, sodium hydroxide solution of 2 M and / or hydrochloric acid solution of 2 M to adjust the pH to 4.0 - 6.0, water for injection - up to 1.0 ml.

Description:A clear, colorless solution.

Pharmacotherapeutic group:Local anesthetic

ATX: & nbsp

N.01.B.B Amides

N.01.B.B.09 Ropivacaine

Pharmacodynamics:

Solution of the drug Ropivacaine is a sterile isotonic aqueous solution, contains no preservatives and is intended for single use only, ropivacaine 8.1 pKa; distribution coefficient - 141 (n-octanol / phosphate buffer pH 7.4 at 25^FROMFROM).

Ropivacaine is a local long-acting amide type anesthetic that is a pure enantiomer. Has both anesthetic and analgesic effect. High doses of ropivacaine are used for local anesthesia in surgical interventions, low doses of the drug provide analgesia (sensory block) with a minimal and non-progressive motor block.The duration and intensity of the blockade caused by ropivacaine, the addition of epinephrine is not affected. By reversibly blocking the potential-dependent sodium channels, it prevents the generation of pulses in the endings of the sensory nerves and impulses along the nervous fibers.

Like other local anesthetics, it can affect other excitable cell membranes (for example, in the brain and myocardium). If an excessive amount of local anesthetic reaches the systemic blood flow in a short period of time, signs of systemic toxicity may appear. Signs of toxicity from the central nervous system precede signs of toxicity from the cardiovascular system, as observed at lower concentrations of ropivacaine in plasma (see section "Overdose").

Direct action of local anesthetics on the heart includes a slowing of conduction, a negative inotropic effect and, in severe overdose, arrhythmias and cardiac arrest. Intravenous administration of high doses of ropivacaine leads to the same effects on the heart.

Intravenous infusions of ropivacaine to healthy volunteers showed its good tolerability.

Indirect cardiovascular effects (decrease in blood pressure, bradycardia), which can occur after epidural administration of ropivacaine, are due to the emerging sympathetic blockade.

Pharmacokinetics:

Absorption:

The concentration of ropivacaine in the blood plasma depends on the dose, the route of administration and the degree of vascularization of the injection site. The pharmacokinetics of ropivacaine is linear, the maximum concentration (Cmax) is proportional to the administered dose.

After epidural administration ropivacaine completely absorbed. Absorption is biphasic, the half-life period (T1 / 2) for the two phases is 14 minutes and 4 hours, respectively. The slowing down of the elimination of ropivacaine is determined by slow absorption, which explains the longer T1/ 2 after epidural administration compared with intravenous administration.

Distribution:

The total plasma clearance of ropivacaine is 440 ml / min, the plasma clearance of the unbound substance is 8 l / min, the renal clearance is 1 ml / min, the volume of distribution in the equilibrium state is 47 l, the hepatic extraction is about 0.4, T1 / 2- 1.8 h . Ropivacaine intensively binds to blood plasma proteins (mainly with al- acid glycoproteins), the unbound fraction of ropivacaine is about 6%. Long-term epidural infusion of ropivacaine leads to an increase in the total content of the drug in the blood plasma, which is due to an increase in the content of acidic glycoproteins in the blood after surgery, with the concentration unrelated, pharmacologically active form of ropivacaine in blood plasma is changed to a much lesser degree than the total concentration of ropivacaine.

Ropivacaine penetrates well through the placental barrier with rapid achievement of equilibrium over the unbound fraction. The degree of binding to blood plasma proteins in the fetus is less than that of the mother, which leads to lower concentrations of ropivacaine in fetal plasma compared to the total concentration of ropivacaine in the mother's blood plasma.

Metabolism:

Ropivacaine is actively metabolized in the body, mainly by aromatic hydroxylation. 3-hydroxyropivacaine (conjugated + unconjugated) is found in the blood plasma. 3-hydroxy and 4-hydroxypiroquin have a weaker local anesthetic effect compared to ropivacaine.

Elimination:

After intravenous administration, 86% of ropivacaine is excreted in the urine and only about 1% of the urinary excreted is excreted unchanged. About 37% of 3-hydroxypropivacaine, the main metabolite of ropivacaine, is excreted in the urine mainly in conjugated form.

1-3% of ropivacaine is excreted in the urine in the form of the following metabolites: 4-hydroxyropivacaine, N-dealkylated metabolites and 4-hydroxy-dealkylated ropivacaine.

There is no data on the racemization of ropivacaine in vivo.

Indications:

In a concentration of 2 mg / ml Ropivacaine apply according to the following indications:

Coping of acute pain syndrome in adults and children over 12 years of age:

- prolonged epidural infusion or intermittent bolus administration, for example, to eliminate postoperative pain or anesthetic delivery;

- blockade of individual nerves and infiltration anesthesia;

- prolonged blockade of peripheral nerves by infusion or bolus injections (with postoperative pain).

Kupirovanie acute pain syndrome in children from 1 year to 12 years (inclusive):

- single and prolonged blockade of peripheral nerves.

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

- caudal epidural block;

- prolonged epidural infusion.

In a concentration of 5 mg / ml Ropivacaine apply according to the following indications:

Anesthesia in surgical interventions in adults and children over 12 years of age:

- intrathecal blockade.

Kupirovanie acute pain in pediatrics:

- blockade of peripheral nerves in children from 1 year to 12 years inclusive.

At a concentration of 7.5 mg / ml and 10 mg / ml Ropivacaine apply in adults and children over 12 years of age according to the following indications:

Anesthesia during surgical interventions:

- epidural blockade in surgical interventions, including cesarean section;

- blockade of large nerves and nerve plexuses;

- blockade of individual nerves and infiltration anesthesia.

Intra-articular injection with arthroscopy of the knee joint.

Contraindications:

Hypersensitivity to the active substance, to any of the auxiliary substances or other local anesthetics of the amide type.

It is necessary to take into account the general contraindications for each type of anesthesia, regardless of the anesthetic used.

A drug Ropivacaine is contraindicated for intravenous regional anesthesia, a "large" blockade, in patients with hypovolemia and paracervical anesthesia in obstetrics.

In a concentration of 5 mg / ml Ropivacaine has the following contraindications:

In view of the lack of sufficient clinical observations, the use of ropivacaine in children younger than 1 year is not recommended, as is the intrathecal administration of the drug.

Carefully:

Weakened elderly patients or patients with severe concomitant diseases, such as blockade of intracardiac conduction II and III degrees (sinoatrial, atrioventricular, intraventricular), progressive liver disease, severe hepatic insufficiency, severe chronic renal failure, with hypovolemic shock therapy, acute porphyria, childhood, pregnancy and lactation. For these patient groups, regional anesthesia is often preferred. When carrying out "large" blockades in order to reduce the risk of developing severe adverse events, it is recommended to pre-optimize the patient's condition and also adjust the dose of anesthetic.

Patients on a diet with sodium restriction must take into account the sodium content in the preparation.

Caution should be exercised when injecting local anesthetics in the head and neck area, due to the possible increased incidence of serious side effects.

Caution should be used when using Ropivacaine 2 mg / ml, 7.5 mg / ml and 10 mg / ml in the following categories of patients:

With intraarticular administration of the drug, caution should be exercised if there is a suspected recent extensive injury to the joint or a surgical operation with the opening of extensive joint surfaces, due to the possibility of increased absorption of the drug and a higher concentration of the drug in the plasma.

Particular attention should be paid to the use of the drug in children under 6 months due to immaturity of organs and functions.

Pregnancy and lactation:

Pregnancy:

There was no evidence of the effect of ropivacaine on fertility and reproductive function, as well as teratogenic effects. There have been no studies to evaluate the possible effect of ropivacaine on fetal development in women.

Ropivacaine can be used in pregnancy only if the expected benefit for the mother exceeds the potential risk to the fetus (in obstetrics use of the drug for anesthesia oranalgesia is well founded).

Lactation:

The isolation of ropivacaine or its metabolites with breast milk has not been studied. Based on the experimental data, the dose of the drug given to the newborn is presumably 4% of the dose given to the mother (ie, the total dose of ropivacaine affecting the baby during breastfeeding is significantly less than the dose that can be given to the newborn when the mother's anesthetic is administered childbirth). If you need to use the drug during breastfeeding, consider the ratio of potential benefits to the mother and the possible risk to the baby.

Dosing and Administration:

The drug is used for epidural, spinal, infiltration and conduction anesthesia.

Ropivacaine should be used only by specialists with sufficient experience in local anesthesia, or under their supervision, with equipment and medications for resuscitation. Prior to the execution of large blockades, intravenous catheters should be installed.

Adults and children over 12 years of age:

In general, anesthesia in surgical interventions requires higher doses and more concentrated solutions of the drug than with the use of an anesthetic for analgesia. When using an anesthetic for analgesia, a dose of 2 mg / ml is usually recommended. For intraarticular administration, a dose of 7.5 mg / ml is recommended. Ropivacaine in a dose of 10 mg / ml is recommended for epidural anesthesia, when complete motor blockade is necessary for operations.

The doses indicated in Tables 1 and 2 are considered sufficient to achieve a reliable blockade and are indicative for the use of the drug in adults and children over 12 years of age, since there is an individual variability in the rate of progression of the blockade and its duration.

The data in Tables 1 and 2 are an indicative guide for the dosing of the preparation for the most commonly used blockades. When choosing a dose of the drug should be based on clinical experience, taking into account the physical condition of the patient.

Table 1. Recommendations for dosing the drug Ropivacaine for adults and children over 12 years in concentrations of 2 mg / ml. 7.5 mg / ml and 10 mg / ml:

	Concentration preparation (mg / ml)	Scope solution (ml)	Dose (mg)	Start actions (min)	Duration of action (h)
Anesthesia during surgical interventions:
Epidural anesthesia at the lumbar level:
Surgical interventions	7,5	15-25	113-188	10-20	3-5
Surgical interventions	10,0	15-20	150-200	10-20	4-6
Cesarean section	7,5	15-20	113-150	10-20	3-5
Epidural anesthesia at the thoracic level:
Postoperative pain blockade and surgery	7,5	5-15	38-113	10-20	-
Blockade of major plexus:
For example, blockade of the brachial plexus	7,5	10-40	75 - 300*	10-25	6- 10
Conductor and infiltration anesthesia	7,5	1-30	7,5-225	1-15	2-6
Kupirovanie acute pain syndrome:
Epidural introduction at the lumbar level:
Bolus	2,0	10-20	20-40	10- 15	0,5-1,5
Periodic administration (for example, with anesthetic delivery)	2,0	10-15 (the minimum interval is -30 minutes)	20-30
Extended infusion for:
anesthesia of childbirth	2,0	6-10 ml / hr	12-20 mg / hr	-	-
after operating anesthesia	2,0	6-14 ml / hr	12-28 mg / hr	-	-
Blockade of peripheral nerves:
For example, blockade of the femoral nerve or interstitial blockade (prolonged infusions or repeated injections)	2,0	5-10 ml / hr	10-20 mg / hr	-	-
Epidural introduction at the thoracic level:
Extended infusion (for example, for postoperative analgesia)	2,0	6-14 ml / hr	12-28 mg / hr	-	-
Conducting blockade and infiltration anesthesia	2,0	1 - 100	2-200	1-5	2-6
Intra-articular administration:
Arthroscopy of the knee joint **	7,5	20	150***	-	2-6

* The dose for blockade of large plexus plexuses should be selected according to the site of administration and the patient's condition. Blockade of the brachial plexus with interlacial and supraclavicular access can be associated with a high incidence of serious adverse reactions, regardless of the local anesthetic used.

** There have been reports of cases of chondrolisis in postoperative prolonged intra-articular infusion of local anesthetics. Ropivacaine should not be used for prolonged intra-articular infusion.

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

Table 2. Recommendations for dosing of the drug Ropivacaine for adults and children over 12 years in a concentration of 5 mg / ml:

	Concentration preparation (mg / ml)	Scope solution (ml)	Dose (mg)	Start actions (min)	Duration of action (h)
Anesthesia during surgical interventions:
Intrathecal blockade:
Surgical interventions	5,0	3-4	15-20	1-5	2-6

To familiarize with the factors influencing the method of execution of individual blockades, and with the requirements for specific groups of patients, standard guidelines should be used.

To prevent an anesthetic from entering the vessel, an aspirate sample must be performed before and during the administration of the preparation. If it is intended to use the drug in a high dose, it is recommended to enter a trial dose of 3-5 ml of lidocaine with epinephrine. A random intravascular injection is recognized by a temporary increase in the heart rate, and a random intrathecal injection is indicated by the spinal block. If toxic symptoms occur, discontinue the drug immediately.

Before and during the administration of Ropivacaine (which should be done slowly or by increasing sequential doses of the drug at a rate of 25-50 mg / min), vital functions must be closely monitored patient and maintain verbal contact with him.

Single administration of ropivacaine in a dose of up to 250 mg with epidural blockade for surgery is usually well tolerated by patients.

When the brachial plexus blockade using 40 ml of the preparation Ropivacaine 7.5 mg / ml, the maximum plasma concentration of ropivacaine in some patients may reach values characterized by mild symptoms of toxicity in the central nervous system.Therefore, the use of a dose above 40 ml of the drug Ropivacaine 7.5 mg / ml (300 mg of ropivacaine) is not recommended.

With prolonged blockade by prolonged infusion or repeated bolus administration, consideration should be given to the possibility of creating toxic concentrations of anesthetic in the blood and local nerve damage. The administration of ropivacaine for 24 hours at a dose of up to 800 mg in total for surgical interventions and for postoperative analgesia, and prolonged epidural infusion after surgery at a rate of up to 28 mg / h for 72 hours is well tolerated by adult patients.

For the relief of postoperative pain, the following regimen is recommended: if the epidural catheter was not installed during surgery, epidural blockade with a bolus injection of Ropivacaine (7.5 mg / ml) is performed after its installation. Analgesia is supported by infusion of the drug Ropivacaine (2 mg / ml). In most cases, to relieve postoperative pain from moderate to severe, infusion at a rate of 6-14 ml / h (12-28 mg / h) provides adequate analgesia with minimal non-progressive motor blockade (using this technique, there was a significant decrease in the need for opioid analgesics ).

For postoperative analgesia, Ropivacaine (2 mg / ml) can be administered continuously as an epidural infusion for 72 hours without fentanyl or in combination with it (1-4 μg / ml). When using the drug Ropivacaine 2 mg / ml (6-14 ml / h), adequate anesthesia was provided in most patients. The combination of the drug Ropivacaine and fentanyl led to an improvement in analgesia, causing side effects inherent in narcotic analgesics.

The use of the drug Ropivacaine in concentrations above 7.5 mg / ml with caesarean section has not been studied.

Renal insufficiency

Typically, with the introduction of a single dose or short-term therapy for patients with impaired renal function, a dose change is not required.

Liver failure

Ropivacaine is metabolized in the liver and, as a result, should be used with caution in patients with serious liver disease. Repeated doses may need to be reduced because of delay in excretion.

Patients, suffering from hypovolaemia

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

Table 3.Recommendations for dosing of the drug Ropivacaine for children from 0 to 12 years in a concentration of 2 mg / ml:

	Concentrations of the drug (mg / ml)	Volume of solution (ml / kg)	Dose (mg / kg)
Kupirovanie acute pain syndrome (intraoperative and postoperative):
Caudal epidural administration:
Blockade in the area below Th_XII in children weighing up to 25 kg	2,0	1	2
Extended epidural infusion in children weighing up to 25 kg
Age from 0 to 6 months:
Bolus *	2,0	0,5-1	1-2
Infusion up to 72 hours	2,0	0.1 ml / kg / h	0.2 mg / kg / h
Age from 6 to 12 months:
Bolus *	2,0	0,5-1	1-2
Infusion up to 72 hours	2,0	0.2 ml / kg / h	0.4 mg / kg / h
Age from 1 to 12 years inclusive:
Bolus **	2,0	1	2
Infusion up to 72 hours	2,0	0,2 ml / kg / h	0.4 mg / kg / h

* Smaller doses from the proposed interval are recommended for epidural administration at the thoracic level, while larger doses are recommended for epidural administration at the lumbar or caudal levels.

** Recommended for epidural administration at the lumbar level. It is reasonable to reduce the bolus dose for epidural analgesia at the thoracic level.

Table 4. Recommendations for dosing the drug Ropivacaine for children from 1 year to 12 years at a concentration of 5 mg / ml:

	Concentrations preparation (mg / ml)	Volume of solution (ml / kg)	Dose (mg / kg)
Pain relief of acute pain syndrome (intraoperative and postoperative):
Blockade peripheral first in children from 1 to 12 years of age inclusive:
For example, for blockade of the ilio-inguinal nerve	5,0	0,6	3

The doses indicated in Tables 3 and 4 are the guide to the use of the drug in pediatric practice. At a certain time, there is an individual variability in the speed of the development of the unit and its duration.

Children with overweight often require a gradual decrease in the dose of the drug; while it is necessary to be guided by the "ideal" body weight of the patient. For background information on the factors that affect the methods of performing individual blockades and the requirements for specific groups of patients, refer to specialized manuals. The volume of the caudal epidural solution and the bolus volume for epidural administration should not exceed 25 ml for any patient.

To prevent unintentional intravascular injection of anesthetic, an aspirate sample should be carefully performed before and during the administration of the preparation.During the administration of the drug, the vital functions of the patient must be closely monitored. If toxic symptoms occur, discontinue the drug immediately.

Single administration of ropivacaine in a dose of 2 mg / ml (2 mg / kg, 1 ml / kg solution volume) for postoperative caudal analgesia provides adequate analgesia below the T levelh_XII in most patients. Children older than 4 years are well tolerated doses up to 3 mg / kg. The volume of the administered solution for epidural administration at the caudal level can be changed to achieve a different the prevalence of the sensory block, as described in the specialized manuals. Regardless of the type of anesthesia, bolus administration of the calculated dose is recommended.

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

Instructions for use of the solution

The solution does not contain preservatives and is intended for single use only.Subject to immediate use, after opening the vial, unused residue of the drug is destroyed.

Before use, the drug should be examined carefully. The solution for injections is only suitable if it is transparent, there are no visible mechanical particles, and the container is not damaged.

Any amount of solution remaining in the vial after use should be destroyed.

In view of the lack of sufficient clinical observations, it is not recommended to apply ropivacaine in a dosage of 5 mg / ml in children under the age of 1 year.

Side effects:

Unwanted reactions to Ropivacaine are similar to reactions to other local anesthetics of the amide type. They should be distinguished from the physiological effects arising from the blockade of the sympathetic nerves on the background of epidural anesthesia, such as lowering blood pressure, bradycardia, or effects associated with drug administration techniques such as spinal hematoma, local nerve damage, meningitis, post-puncture headache, epidural abscess.

Side effects inherent in local anesthetics

From the central and peripheral nervous system

Possible neuropathy and impaired spinal cord function (anterior spinal artery syndrome, arachnoiditis, horse tail syndrome), are usually associated with the technique of conducting regional anesthesia, and not with the action of the drug.

As a result of a random intrathecal injection of the epidural dose, a complete spinal block can occur.

Serious complications are possible with systemic overdose and unintentional intravascular administration of the drug (see section "Overdose").

Acute Systemic Toxicity

Ropivacaine can cause acute systemic toxic reactions with high doses or with a rapid increase in its concentration in the blood with accidental intravascular administration of the drug or its overdose (see section "Pharmacological properties" and "Overdose").

The most common side effects

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

The most common (> 1%) reported the following side effects, which were are regarded as having clinical significance, regardless of whether a cause-and-effect relationship was established with the use of anesthetic: lowering blood pressure (BP), nausea, bradycardia, vomiting, paresthesia, fever, headache, urinary retention, dizziness, chills, increased blood pressure, tachycardia, hypesthesia, anxiety.

The frequency of undesirable effects is as follows: Very often (> 1/10); Often (> 1/100, <1/10); Infrequently (> 1/1000, <1/100); Rarely (> 1/10000, <1/1000); Very rarely (<1/10000), including individual messages.

From the cardiovascular system: very often - a decrease in blood pressure; often - bradycardia, tachycardia, increased blood pressure; rarely - a syncope; rarely - arrhythmia, cardiac arrest.

From the gastrointestinal tract (GIT): very often - nausea; often vomiting **.

From the nervous system: often - paresthesia, dizziness, headache; infrequent anxiety, symptoms of toxicity from the side of the central nervous system (seizures, large seizures, paresthesia in the perioral zone, dysarthria, numbness of the tongue, visual impairment, ringing in the ears, hyperacia, tremor,muscle twitching) ***, hypoesthesia.

From the genitourinary system: often - urinary retention.

From the respiratory system: infrequent - shortness of breath, shortness of breath.

Are common: often - back pain, chills, fever; infrequently - hypothermia; rarely - allergic reactions (anaphylactic reactions, angioedema, urticaria).

* Decrease in blood pressure occurs in children often.

** Vomiting is very common in children.

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

Overdose:

Acute Systemic Toxicity

In case of accidental intravascular injection, blockages of nerve plexuses or other peripheral blockades were accompanied by seizures.

In the case of an incorrect injection of an epidural dose of an anesthetic intrathecally, a complete spinal block may occur.

A random intravascular injection of an anesthetic can cause an immediate toxic reaction.

When an overdose during regional anesthesia symptoms of systemic toxic reactions appear in a delayed manner 15-60 min after injection due to a slow increase in the concentration of local anesthetic in the blood plasma.Systemic toxicity, in the first place, is 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 result from (accidental) intravascular injection, overdose or exceptionally high adsorption from highly vascularized areas. CNS reactions are similar for all local anesthetics of the amide type, while cardiovascular reactions 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 mistaken for the patient's neurotic behavior). With the progression of intoxication, there may be a loss of consciousness,seizures of seizures lasting from a few seconds to several minutes, accompanied by a violation of breathing, the rapid development of hypoxia and hypercapnia due to increased muscle activity and inadequate ventilation. In severe cases, even stopping breathing may occur. Emerging acidosis, hyperkalemia, hypocalcemia increases the toxic effects of anesthetic.

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

The cardiovascular system

Disorders from the cardiovascular system are signs of more serious complications. Decrease in blood pressure, bradycardia, arrhythmia and, in some cases, even cardiac arrest may occur due to the high systemic concentration of local anesthetics. In rare cases, cardiac arrest is not accompanied by a previous symptomatology of the CNS. In studies on volunteers, intravenous infusion of ropivacaine led to inhibition of conduction and contractile the ability of the heart muscle.Symptoms from the cardiovascular system usually preceded by manifestations of toxicity from the central nervous system, which can be overlooked if the patient is sedated (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 experienced by children in describing symptoms, or in the case of regional anesthesia combined with general anesthesia.

Acute Toxicity Treatment

When the first signs of acute systemic toxicity appear, discontinue the drug immediately.

When there are seizures and symptoms of CNS depression, the patient needs adequate treatment, whose goal is to maintain oxygenation, arrest seizures, maintain the cardiovascular system. It is necessary to provide oxygenation by oxygen, and if necessary - transition to artificial ventilation of the lungs. If after 15-20 seconds of seizures do not stop, anticonvulsants should be used: thiopental sodium 1-3 mg / kg IV (ensures rapid arrest of seizures) or diazepam 0.1 mg / kg IV (the effect develops more slowly compared with the action of sodium thiopental). Suxamethonium 1 mg / kg quickly cures seizures, but requires intubation and artificial ventilation of the lungs.

When oppressing the cardiovascular system (lowering blood pressure, bradycardia), intravenous injection of 5-10 mg of ephedrine is necessary, and if necessary, repeat after 2-3 minutes. With the development of circulatory insufficiency or cardiac arrest, standard resuscitation should begin immediately. It is vitally important to maintain optimal oxygenation, ventilation and circulation of blood, and also to correct acidosis. Heart failure may require longer resuscitation.

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

Interaction:

This drug should not be mixed with other drugs.

Simultaneous use of the drug Ropivacaine with local anesthetics, drugs structurally similar to local anesthetics of the amide type or drugs that depress the central nervous system (CNS) can enhance the toxic effects of 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 ropivacaine may precipitate because it is slightly soluble at a pH above 6.0.

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

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

In vitro ropivacaine hydrochloride is a competitive inhibitor of isoenzyme CYP2D6, At the same time, inhibition of this isoenzyme is not achieved with the concentration of the drug in plasma used in practice.

Special instructions:

Anesthesia should be conducted by experienced specialists. It is necessary to have equipment and medicines for resuscitation. Before starting large blockades, an intravenous catheter should be installed.

Regional and local anesthesia should be carried out by experienced specialists in an appropriately equipped room with availability of ready-to-use equipment and preparations necessary for cardiac monitoring and resuscitation. Personnel performing anesthesia should be qualified and trained in the technique of performing anesthesia, should be familiar with the diagnosis and treatment of systemic toxic reactions, adverse events and reactions, and other complications.

Complications of unintentional subarachnoidal administration may be spinal block with stopping breathing and lowering blood pressure. Seizures develop more often with blockade of the brachial plexus and epidural blockade, probably due to accidental intravascular injection or rapid absorption at the injection site. Execution of peripheral nerve blockages may require the injection of a large volume of local anesthetic into areas with a large number of vessels, often near large vessels, which increases the risk of intravascular injection and / or rapid systemic absorption, which can lead to high plasma concentrations of the drug.

Some procedures associated with the use of local anesthetics, such as injections in the head and neck, may be accompanied by an increased incidence of serious side effects, regardless of the type of local anesthetic used. Care must be taken to prevent injection into the area of inflammation.

Care should be taken when administering the drug to patients with blockade of intracardiac conductance of II and III degrees, patients with severe renal failure, elderly and weakened patients.

There are reports of rare cases of cardiac arrest with the use of the drug Ropivacaine for epidural anesthesia or peripheral nerve blockages, especially after accidental intravascular drug administration, in elderly patients and in patients with concomitant cardiovascular diseases.

In some cases, resuscitation was difficult. Heart failure, as a rule, requires more prolonged resuscitation.

Because the Ropivacaine metabolized in the liver, caution should be exercised when using the drug in patients with severe liver disease; in some cases, because of delayed elimination, it may be necessary to reduce re-injected doses of anesthetic.

Usually, in patients with renal insufficiency, when administering the drug once or when using the drug for a short period of time, it is not necessary to adjust the dose. However, acidosis and a decrease in the concentration of proteins in the blood plasma, often developing in patients with chronic renal insufficiency, may increase the risk of systemic toxic effects of the drug (see section "Method of administration and dose"). The risk of systemic toxicity is also increased when the drug is used in patients with a loweredbody weight and patients with hypovolemic shock. Epidural anesthesia can lead to a decrease in blood pressure and bradycardia. Introduction vasoconstrictors or an increase in the volume of circulating blood may reduce the risk of such side effects. It should be timely corrected the decrease in blood pressure by intravenous injection of 5-10 mg of ephedrine, if necessary, repeat the introduction.

Patients receiving treatment with antiarrhythmic drugs of the III class (for example, amiadorin) should be closely monitored, ECG monitoring is recommended in connection with the risk of increasing cardiovascular effects.

Avoid prolonged use of the drug Ropivacaine in patients taking potent inhibitors of isoenzyme CYP1A2 (such as, fluvoxamine and enoxacin).

Consideration should be given to the possibility of cross-over-hypersensitivity with simultaneous application of the drug Ropivacaine with other local anesthetics of the amide type.

Patients on a diet with sodium restriction must take into account the sodium content in the preparation.

The use of the drug in newborns requires consideration of the possible immaturity of the organs and the physiological functions of the newborn. The clearance of the unbound fraction of ropivacaine and pipeloxylidine (PPK) depends on the body weight and age of the child in the first years of life. The influence of age is expressed in the development and maturity of liver function, the clearance reaches a maximum value at the age of about 1-3 years. The half-life of ropivacaine is 5-6 hours for newborns and children aged 1 month compared with 3 hours in older children. In connection with the insufficient development of liver function system exposure of ropivacaine is higher in newborns, moderately higher - in children from 1 to 6 months compared with older children. Significant differences in the concentrations of ropivacaine in the blood plasma of newborns, identified in clinical studies,suggest an increased risk of systemic toxicity in this group of patients, especially with prolonged epidural infusion.

The recommended doses for newborns are based on limited clinical data.

When using ropivacaine in neonates, monitoring systemic toxicity (control of signs of toxicity from the central nervous system, ECG, control of blood oxygenation) and local neurotoxicity, which should be continued 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 / ml, as well as intrathecal application of the drug Ropivacaine in children it was not investigated.

Ropivacaine may potentially have porphyrinogenic properties and can be used in patients with acute porphyria diagnosis only in cases where there is no safer alternative. In the case of hypersensitivity patients should take the necessary precautions.

There have been reports of cases of chondrolisis in postoperative prolonged intra-articular infusion of local anesthetics. In most of the cases described, an infusion into the shoulder joint was performed.Causal relationship with the use of anesthetics is not established. Ropivacaine Do not use for prolonged intra-articular infusion.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Solution for injection 2 mg / ml, 5 mg / ml, 7.5 mg / ml, 10 mg / ml.

Packaging:

For 10 or 20 ml in bottles of colorless neutral glass I hydrolytic class, sealed with rubber stoppers, with a rolling aluminum caps with a plastic lid type "flip-off". Each label is labeled.

5 bottles are placed in a contour mesh package.

1 contour pack with instructions for use is placed in a pack of cardboard.

Storage conditions:

3 years.

Do not use after the expiry date printed on the package.

Shelf life:

Store at a temperature not exceeding 30 ° C. Do not freeze. Keep out of the reach of children.

Terms of leave from pharmacies:On prescription

Registration number:LP-004182

Date of registration:15.03.2017

Expiration Date:15.03.2022

The owner of the registration certificate:BIOCAD, CJSC BIOCAD, CJSC Russia

Manufacturer: & nbsp

BIOCAD, CJSC Russia

Information update date: & nbsp04.04.2017

Illustrated instructions

Instructions

Ropivacaine (Ropivacaine)