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

Excipients: sodium chloride 8.6 mg, 7.5 mg and 7.1 mg, respectively, 2 M sodium hydroxide solution and / or 2 M hydrochloric acid solution to adjust the pH to 4.0 - 6.0, water for injection up to 1 , 0 ml.

Description:

A clear, colorless solution.

Characteristic

Drug solution Naropin® is a sterile isotonic aqueous solution, contains no preservatives and is intended for single use only. pKa of ropivacaine 8.1; the partition coefficient is 141 (n-octanol / phosphate buffer pH 7.4 at 25 ° C).

Pharmacotherapeutic group:Local anesthetic

ATX: & nbsp

N.01.B.B Amides

N.01.B.B.09 Ropivacaine

Pharmacodynamics:

Ropivacaine is the first local anesthetic of the long-acting amide type, which 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. Reversibly blocking the potential-dependent sodium channels, prevents the generation of pulses in the endings of the sensory nerves and impulses along nerve 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:

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 are linear, the maximum concentration (C_max) is proportional to the administered dose.

After epidural administration ropivacaine completely absorbed. Absorption is biphasic, half-life (T_1/2) 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 T_1/2 after epidural administration compared with intravenous administration.

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, T_1/2 1.8 hours. Ropivacaine intensively binds to blood plasma proteins (mainly with a 1-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, while the concentration of unrelated, pharmacologically active form of ropivacaine in blood plasma varies much less than the total concentration of ropivacaine.

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

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-hydroxyropivacaine, 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 evidence of racemisation of ropivacaine in vivo.

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. Kupirovanie acute pain syndrome:

- prolonged epidural infusion or a periodic bolus administration, for example,for elimination of postoperative pain or anesthesia of childbirth;

- blockade of individual nerves and infiltration anesthesia;

- prolonged blockade of peripheral nerves;

- intraarticular injection.

Kupirovanie acute pain in pediatrics:

- caudal epidural blockade in newborns and children up to 12 years of age, inclusive;

- prolonged epidural infusion in newborns and children up to 12 years of age, inclusive.

Contraindications:

Hypersensitivity to the components of the drug.

Known hypersensitivity to local anesthetics of the amide type.

Carefully:

Weakened elderly patients or patients with severe concomitant diseases, such as blockade of intracardiac conductivity of II and III degrees (sinoatrial, atrioventricular, intraventricular), progressive liver disease, severe hepatic insufficiency, severe chronic renal failure, with hypovolemic shock therapy. 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 recommendedpre-optimize the patient's condition, and adjust the dose of anesthetic. Caution should be exercised when injecting local anesthetics in the head and neck area, due to the possible increased incidence of serious side effects. 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.

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

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.

Naropin® can be used during pregnancy only,if the expected benefit for the mother exceeds the potential risk for the fetus (in obstetrics use of the drug for anesthesia or analgesia is well justified).

Studies of the effect of the drug on reproductive function were carried out on animals. In studies on rats ropivacaine did not affect fertility and reproduction in two generations. When maximum doses of ropivacaine were administered to pregnant rats, the mortality of offspring increased in the first three days after delivery, which may be explained by the toxic effect of ropivacaine on the mother,leading to a violation of the maternal instinct.

Studies of teratogenicity in rabbits and rats have not shown the side effects of ropivacaine on organogenesis or fetal development in the early stages. Also, during the perinatal and postnatal studies in rats receiving the maximum tolerated dose of the drug, there were no side effects at late stages of fetal development, labor, lactation, viability, or growth in offspring.

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 received by the newborn is presumed to be 4% of the dose given to the mother (concentration of the drug in milk / plasma concentration of the drug). The total dose of ropivacaine affecting the baby during breastfeeding is significantly less than the dose that can get into the Fetus with the introduction of an anesthetic mother during 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:

Naropin® should only be used by specialists who have sufficient experience in conducting local anesthesia, or under their supervision.

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.

The doses indicated in Table 1,are considered sufficient to achieve a reliable blockade and are indicative when using the drug in adults, since there is an individual variability in the rate of development of the blockade and its duration.

The data in Table 1 is an indicative guide for dosing the drug 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 of Naropin® for adults:

		Concentration			Scope			Dose			Start			The term
		the			solution			(mg)			actions			the

Anesthesia during surgical interventions:
Epidural anesthesia at the lumbar level:
Surgical interventions		7,5			15-25			113-188			10-20			3-5
		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 anesthetic blockade and surgical interventions	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
Conducting 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, anesthesia childbirth)	2,0			10-15 (minimal interval - 30 min)			20-30
Extended infusion for:
-efficination of childbirth	2,0			6-10 ml / hr			12-20 mg / hr
-after surgical analgesia	2,0			6-14 ml / hr			12 to 28 mg / hr
Blockade of peripheral nerves:
For example, blockade femoral nerve or interlace blockade (extended infusion or repeated injections)	2,0			5-10 ml / hr			10-20 mg / hr
Epidural administration at the thoracic level:
Prolonged infusion (for example, for postoperative th anesthesia)			2,0			6-14 ml / hr			12-28 mg / hr
Conductive blockade and infiltration anesthesia			2,0			1 -100			2-200			1-5			2-6
Intra-articular administration
Arthroscopy 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. Naropin® should not be used for prolonged intra-articular infusion.

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

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 Naropin® (which should be done slowly or by increasing sequential doses of the drug at a rate of 25-50 mg / min), the vital functions of the patient must be closely monitored and verbal contact maintained.

Single administration of ropivacaine in a dose of up to 250 mg with epidural blockade for surgery is usually well tolerated by patients.With blockade of the brachial plexus with 40 ml of the drug Naropin® 7.5 mg / ml, the maximum plasma concentrations of ropivacaine in some patients can reach a value characterized by mild symptoms of toxicity from the central nervous system. Therefore, the use of a dose above 40 ml of the drug Naropin® 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 scheme of drug use is recommended: if an epidural catheter was not installed during surgery, epidural blockage with a bolus injection of Naropin® (7.5 mg / ml) is performed after its installation.Analgesia is maintained by the infusion of Naropin® (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 consumption in opioid analgesics).

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

The use of Naropin® in concentrations above 7.5 mg / ml with caesarean section has not been studied.

Table 2. Recommendations for dosing of Naropin® for children under 12:

	Concentration of the preparation (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
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.

The doses indicated in Table 2 are the guide to the use of the drug in pediatric practice. At the same time, there is an individual variability in the rate of development of the block 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 (at a rate of 2 mg / kg solution volume of 1 ml / kg) for postoperative caudal analgesia provides adequate analgesia below the level Th_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 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 intrathecal use of the drug Naropin® in children has not been studied. The use of Naropin® in preterm infants has not been studied.

Instructions for use of the solution

The solution does not contain preservatives and is intended for single use only. Any amount of solution left in the container after use should be destroyed.

The unopened container with the solution must not be autoclaved.

Unopened blister pack provides sterility of the outer surface container and is preferred for use in conditions requiring sterility.

Side effects:

Undesirable reactions to Naropin® are similar to reactions with 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 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

Naropin® can cause acute systemic toxic reactions when using 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.

Most frequently (> 1%), the following side effects were noted, which were regarded as having clinical significance, regardless of whether the cause-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 (> 1/10 000, <1/1 000); Very rarely (<1/10 000), including individual messages.

Often	From the cardiovascular system: a decrease in blood pressure * From the side of the gastrointestinal tract (GIT): nausea
Often	From the side of the nervous system: paresthesia, dizziness, headache From the cardiovascular system: bradycardia, tachycardia, increased blood pressure From the digestive tract: vomiting ** On the part of the genitourinary system: retention of urination General: back pain, chills, fever
Infrequently	From the nervous system: anxiety, symptoms of toxicity from the side of the central nervous system (seizures, large convulsive seizures,paresthesia in the perioral zone, dysarthria, numbness of the tongue, visual impairment, ringing in the ears, hyperacusia, tremor, muscle cramps), hypoesthesia From the side of the vascular system: a syncope From the respiratory system: shortness of breath, difficult breath General: hypothermia
Rarely	From the cardiovascular system: arrhythmia, cardiac arrest General: allergic reactions (anaphylactic reactions, angioedema, urticaria)

* Decrease in blood pressure occurs in children often.

** Vomiting is very common in children.

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.

In case of an overdose during the regional anesthesia, the symptoms of a systemic toxic reaction appear in a delayed manner 15-60 min after the injection due to a slow increase in the local anesthetic concentration 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 a duration of several 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 contractility of the heart muscle.Symptoms from the cardiovascular system are 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 immediately

stop the drug.

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:

Possible summation of toxic effects with simultaneous administration with other local anesthetics or preparations structurally similar to local anesthetics of the amide type.

The clearance of ropivacaine is reduced to 77% with simultaneous application with fluvoxamine, a potent competitive inhibitor of isoenzyme CYP1A2, Because of the possibility of similar interactions, long-term use of Naropin® should be avoided with fluvoxamine.

Increasing the pH of the solution above 6.0 can lead to the formation of precipitate due to the poor solubility of ropivacaine under the given conditions.

The solution of Naropin® in plastic infusion bags is compatible with the following medicinal products according to its chemical and physical properties:

The concentration of Naropin: 1-2 mg / ml
The solution added	Concentration
Fentanyl	1.0-10.0 μg / ml
Morphine	20.0 - 100.0 μg / ml

Despite the fact that the obtained mixtures retain chemical and physical stability for 30 days at a temperature of no higher than 30 ° C, based on the data on microbiological purity, the resulting mixture of solutions should be used immediately after preparation.

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. Staff providing anesthesia,should be appropriately prepared and familiar with the diagnosis and treatment of possible side effects, systemic toxic reactions and other possible complications (see section "Overdose").

Complication of unintentional subarachnoidal administration may be a spinal block with respiratory arrest and a decrease in blood pressure. Seizures develop more often with blockade of the brachial plexus and epidural block, 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 have been reports of rare cases of cardiac arrest with Naropin® 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. Since Naropin® is 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 underweight patients and patients with hypovolemic shock.

Epidural anesthesia can lead to a decrease in blood pressure and bradycardia. The introduction of vasoconstrictors or an increase in the volume of circulating blood can 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, with. need to repeat the introduction.

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. 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 Naropin® in patients taking potent inhibitors of the CYP1A2 isoenzyme (such as, fluvoxamine, and enoxacin).

Consider the possibility of cross-over-hypersensitivity, while using the drug Naropin® 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 plasma of blood of newborns identified in clinical studies suggest an increased risk of systemic toxicity in this group of patients, especially in continuous epidural infusion.

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

When using ropivacaine in the newborn must monitoring systemic toxicity (toxicity control symptoms from the central nervous system, ECG monitoring blood oxygenation) and local neurotoxicity, which should continue after the end of infusion, due to slow elimination of the drug in the newborn.

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

Naropin® is potentially capable of causing porphyria and can be used in patients diagnosed with acute porphyria 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. Naropin® should not be used for prolonged intra-articular infusion.

Effect on the ability to drive transp. cf. and fur:In addition to the analgesic effect, Naropin® can have a weak transient effect on motor function and coordination. Given the profile of the side effects of the drug, care must be taken when driving vehicles and performing other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

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

Packaging:

Solution for injection 2 mg / ml:

To 20 ml in sealed ampoules from polypropylene. Each ampoule is placed in a contour mesh package. 5 contour mesh packages with instructions for use in a cardboard bundle with the control of the first opening.

100 ml or 200 ml in polypropylene containers (bags), sealed with a butyl rubber stopper and a sheet-shaped aluminum plate.Polypropylene containers (bags) are individually packaged in a polypropylene / paper polypropylene package. For 5 contour packs in a cardboard box with instructions for use.

Solution for injection 7.5 mg / ml and 10 mg / ml:

10 ml in sealed ampoules made of polypropylene. Each ampoule is placed in a contour mesh package. 5 contour mesh packages with instructions for use in a cardboard bundle with the control of the first opening.

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

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014458 / 01

Date of registration:27.01.2010 / 27.03.2017

Expiration Date:Unlimited

The owner of the registration certificate:Aspen Pharma Trading LimitedAspen Pharma Trading Limited

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

ASTRAZENECA, Pty. Ltd. Australia

Representation: & nbspAspen Hells Ltd.Aspen Hells Ltd.

Information update date: & nbsp27.05.2018

Illustrated instructions

Instructions

Naropin® (Naropin®)