Naropin of 2 mg/ml

General characteristics. Structure:

Active agent: ropivakaina hydrochloride monohydrate corresponding of 2,0 mg, 7,5 mg and 10,0 mg of a ropivakain of a hydrochloride.
Excipients: sodium chloride of 8,6 mg, 7,5 mg and 7,1 mg, respectively, 2 M solution of sodium of hydroxide and/or 2 M Acidum hydrochloricum solution for finishing рН to 4,0 - 6,0, water for injections to 1,0 ml.
Description. Transparent colourless solution.
Characteristic
Solution of the drug Naropin® represents sterile isotonic aqueous solution, does not contain preservatives and is intended only for single use. rka of a ropivakain 8,1; a distribution coefficient – 141 (n-oktanol/fosfatny the buffer рН 7,4 at 25 °C).

Pharmacological properties:

Pharmacodynamics. Ropivakain – the first local anesthetic of amide type of long action, being a pure enantiomer. Possesses the action both anesthetizing, and anesthetizing. High doses of a ropivakain are applied to local anesthesia at surgical interventions, low doses of drug provide an analgesia (the touch block) with the minimum and not progressing motor block.
Addition of Epinephrinum does not influence duration and intensity of the blockade caused ropivakainy. Reversibly blocking potentsialzavisimy natrium channels, interferes with generation of impulses in the terminations of sensory nerves and to carrying out impulses on nerve fibrils.
As well as other local anesthetics can exert impact on other excitable cellular membranes (for example, in a brain and a myocardium). If the excess amount of local anesthetic reaches a system blood-groove for a short period, manifestation of signs of system toxicity is possible. Toxicity signs from the central nervous system precede toxicity signs from cardiovascular system as are observed at lower concentration of a ropivakain in plasma (see the section "Overdose").
Direct effect of local anesthetics on heart includes conductivity delay, a negative inotropic effect and, at the expressed overdose, arrhythmias and a cardiac standstill. Intravenous administration of high doses of a ropivakain results in the same effects on heart.
Intravenous infusions of a ropivakain showed to healthy volunteers its good tolerance.
Indirect cardiovascular effects (decrease in the ABP, bradycardia) which can arise after epidural introduction of a ropivakain are caused by the arising sympathetic blockade.

Pharmacokinetics. Concentration of a ropivakain in a blood plasma depends on a dose, a way of introduction and degree of vascularization of area of an injection. The pharmacokinetics of a ropivakain linear, maximum concentration (Cmax) is proportional to the entered dose.
After epidural introduction ропивакаин it is completely absorbed. Absorption has two-phase character, the elimination half-life (T1/2) for two phases makes respectively 14 min. and 4 h. Delay of elimination of a ropivakain is defined by slow absorption that explains longer T1/2 after epidural introduction in comparison with intravenous administration.
The general plasma clearance of a ropivakain – 440 ml/min., plasma clearance of untied substance of 8 l/min, renal clearance of 1 ml/min., distribution volume in an equilibrium condition of 47 l, an indicator of hepatic extraction about 0,4, T1/2 – 1,8 h.
Ropivakain intensively contacts proteins of a blood plasma (mainly with? 1 - turned sour - lymi glycoproteins), the untied fraction of a ropivakain makes about 6%.
Long epidural infusion of a ropivakain leads to increase in the general content of drug in a blood plasma that is caused by increase in maintenance of acid glycoproteins in blood after surgeries, at the same time concentration untied,
pharmacological an active form of a ropivakain in a blood plasma the general concentration of a ropivakain changes in much smaller degree, than.
Ropivakain gets through a placental barrier with bystry achievement of balance on untied fraction. Extent of linkng with proteins of a blood plasma at a fruit is less, than at mother that results in lower concentration of a ropivakain in fruit plasma in comparison with the general concentration of a ropivakain in a blood plasma of mother.
Ropivakain is actively metabolized in an organism, mainly by an aromatic hydroxylation. 3-gidroksiropivakain (not conjugated conjugated +) it is found in a blood plasma. 3 hydroxies and 4-gidroksiropivakain possess weaker mestnoanesteziruyushchy action in comparison with ropivakainy.
After intravenous administration of 86% of a ropivakain it is removed with urine and only about 1% of the drug emitted with urine is removed in not changed look. About 37% of a 3-gidroksiropivakain, the main metabolite of a ropivakain, are removed with urine preferential in the conjugated form.
1-3% of a ropivakain are removed with urine in the form of the following metabolites: 4-gidroksiropivakaina, N-dezalkilirovannykh of metabolites and 4-hydroxy-dezalkilirovannogo of a ropivakain.
There are no data on racemization of a ropivakain of in vivo.

Indications to use:

Anesthesia at surgical interventions:
– epidural blockade at surgical interventions, including Cesarean section;
– blockade of large nerves and neuroplexes;
– blockade of separate nerves and infiltration anesthesia.
Stopping of an acute pain syndrome:
– the prolonged epidural infusion or periodic bolyusny introduction, for example, for elimination of postoperative pain or a labor pain relief;
– blockade of separate nerves and infiltration anesthesia;
– the prolonged blockade of peripheral nerves;
– intra joint injection.
Stopping of an acute pain syndrome in pediatrics:
– caudal epidural blockade at newborns and children to the 12th summer age inclusive;
– the prolonged epidural infusion at newborns and children to the 12th summer age inclusive.

Route of administration and doses:

Наропин® it has to be used only by the specialists having sufficient experience of carrying out local anesthesia or under their observation.
Adults and children are more senior than 12 years:
In general for anesthesia at surgical interventions higher doses and more strong solutions of drug are required, than when using anesthetic for the purpose of anesthesia. When using anesthetic for the purpose of anesthesia the dose of 2 mg/ml is usually recommended. For intra joint introduction the dose of 7,5 mg/ml is recommended.
The doses specified in table 1 are considered sufficient for achievement of reliable blockade and are approximate when using drug at adults as there is an individual variability of speed of development of blockade and its duration.
These tables 1 is the indicative guide to a drug dosing for carrying out the most often used blockade. At selection of a dose of drug it is necessary to be based on clinical experience taking into account a physical condition of the patient.
Table 1. Recommendations about a drug dosing of Naropin® for adults:
                                   Kontsentr-        Volume          the Dose       Began      Duration
                                   ation                  of solution      (ml)        of action   of action
                                   drug          (ml)                             (min.)         (p)
                                   (mg/ml)
Anesthesia at surgical interventions:
Epidural anesthesia at the lumbar level:
Surgical                                      7,5 15 - 25 113 -  188 10 - 20        3 - 5
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 chest level:
Posleoperatsion-                                         7,5 5 - 15 38 - 113 10 - 20        -
Nye anesthetizing
blockade
and surgical
interventions
Blockade of large neuroplexes:
For example, blockade                                7,5 10 - 40 75 - 300 *   10 - 25     6 - 10
brachial plexus
Conduction and                                      7,5 1 - 30 7,5 -     225 1 - 15      2 - 6
infiltration
anesthesia
Stopping of an acute pain syndrome:
Epidural introduction at the lumbar level:
Bolus                                                                 2,0 10 - 20 20 - 40 10 - 15 0,5 - 1,5
Periodic                                        2,0 10 - 15 20 - 30
introduction                                             (minimal-
(for example, at                                   ny inter-
labor pain relief)                       shaft of 30 min.)
The prolonged infusion for:
- labor pain reliefs  of 2,0               6 - 10   ml/h 12 - 20 mg/h  -              -
- after                             2,0               6 - 14   ml/h 12 - 28 mg/h  -              -
operational
anesthesia
Blockade of peripheral nerves:
For example, blockade        of 2,0               5 - 10    ml/h 10 - 20 mg/h   -             -
femoral nerve
or interladder
blockade (prolonged
infusions or
repeated injections
Epidural introduction at the chest level:
The prolonged infusion       of 2,0              6 - 14    ml/h 12 - 28 mg/h   -            -
(for example, for
postoperative
anesthesia)
Conduction                            2,0 1 - 100              2 - 200         1 - 5          2 - 6
blockade and
инфильтрацион
Nye anesthesia
Intra joint introduction
Arthroscopy knee                                    7,5 20 150 ***         -               2-6
joint **
* The dose for blockade of large neuroplexes has to be selected according to an injection site and a condition of the patient. Blockade of a brachial plexus interladder and supraclavicular access can be interfaced with high frequency serious side reactions regardless of the used local anesthetic.
** It was reported about chondrolysis cases at the postoperative prolonged intra joint infusion of local anesthetics. Наропин® it is not necessary to apply to the prolonged intra joint infusion.
*** If Naropin® was in addition used for other types of anesthesia, the maximum dose should not exceed 225 mg.
For acquaintance with the factors influencing a method of performance of separate blockade and with requirements imposed to specific groups of patients it is necessary to use the standard managements.
For prevention of hit of anesthetic to a vessel it is necessary to carry out surely aspiration test to introduction and in the course of administration of drug. If it is supposed to use drug in a high dose, it is recommended to enter a trial dose – 3-5 ml of lidocaine with Epinephrinum. Accidental intravascular introduction is distinguished on temporary increase in heart rate, and accidental intrathecal introduction – on signs of the spinal block. At emergence of toxic symptoms it is necessary to stop administration of drug immediately.
Before introduction and during administration of the drug Naropin® (which should be seen off slowly or by increase in the drug doses entered consistently with speed of 25-50 mg/min.) it is necessary to control carefully the vital functions of the patient and to support with it verbal contact.
Single introduction of a ropivakain in a dose to 250 mg at epidural blockade for carrying out surgical intervention is usually well transferred by patients.
At blockade of a brachial plexus by means of 40 ml of the drug Наропин® 7,5 of mg/ml the maximum plasma concentration of a ropivakain at some patients can reach the value which is characterized by easy symptoms of toxicity from the central nervous system. Therefore use of a dose higher than 40 ml of the drug Наропин® 7,5 of mg/ml (300 mg of a ropivakain) is not recommended.
At long carrying out blockade by the prolonged infusion or repeated bolyusny introduction it is necessary to consider a possibility of creation of toxic concentration of anesthetic in blood and local injury of a nerve. Introduction of a ropivakain during 24 h in a dose to 800 mg totally at surgical interventions and for postoperative anesthesia, and also the prolonged epidural infusion after operation with speed up to 28 mg/h during 72 h well is transferred by adult patients.
For stopping of postoperative pain the following scheme of use of drug is recommended: if the epidural catheter was not established at an operative measure, after its installation epidural blockade is carried out by a bolyusny injection of the drug Naropin® (7,5 mg/ml). The analgesia is supported by drug Naropin® infusion (2 mg/ml). In most cases for stopping of postoperative pain from moderated to expressed, infusion with a speed of 6-14 ml/h (12-28 mg/h) provides an adequate analgesia with the minimum not progressing motive blockade (when using this technique considerable decrease in need for opioid analgetics was observed).
For postoperative anesthesia of Naropin® (2 mg/ml) it is possible to enter continuously in the form of epidural infusion during 72 h without fentanyl or into combinations with it (1-4 mkg/ml). At use of the drug Наропин® 2 of mg/ml (6-14 ml/hour) adequate anesthesia at most of patients was provided. The combination of the drug Naropin® and fentanyl led to anesthesia improvement, causing at the same time the side effects inherent in narcotic analgetics.
Use of the drug Naropin® in concentration higher than 7,5 mg/ml at Caesarian section is not studied.
Table 2. Recommendations about a drug dosing of Naropin® for children up to 12 years:
                                                 Concentration      Volume           Dose
                                                 drug              of solution      (mg/kg)
                                                 (mg/ml)                   (ml/kg)
Stopping of an acute pain syndrome (intraoperative and postoperative):
Caudal epidural introduction:
Blockade in the field of                                                        lower than 2,0 1 2
ThXII at children with a weight
bodies to 25 kg.
The prolonged epidural infusion at children with body weight to 25 kg
Age from 0 to 6 months
Bolus *                                                                              2,0 0,5-1 1-2
Infusion till 72 o'clock                                         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 till 72 o'clock                                         2,0 0,2      ml/kg/h 0,4 mg/kg/h
Age from 1 to 12 years
inclusive
Bolus **                                                             2,0 1
Infusion till 72 o'clock                                         2,0 0,2      ml/kg/h 0,4 mg/kg/h

* Smaller doses from the offered interval are recommended for epidural introduction at the chest level while high doses are recommended for epidural introduction at the lumbar or caudal levels.
** It is recommended for epidural introduction at the lumbar level. The bolus dose decline for an epidural analgesia at the chest level is reasonable.
The doses specified in table 2 are the management to use of drug in pediatric practice. In too time there is an individual variability of speed of development of the block and its duration.
The gradual dose decline of drug often is required from children with excess body weight; at the same time it is necessary to be guided by the "ideal" body weight of the patient. For reference information about factors which influence methods of performance of separate blockade and about requirements imposed to specific groups of patients it is necessary to address the specialized managements. For caudal epidural introduction and bolus volume for epidural introduction 25 ml for any patient should not exceed solution volume.
For prevention of inadvertent intravascular administration of anesthetic it is necessary to carry out carefully aspiration test to introduction and in the course of administration of drug. During administration of drug it is necessary to control the vital functions of the patient carefully. At emergence of toxic symptoms it is necessary to stop administration of drug immediately.
Single introduction of a ropivakain in a dose of 2 mg/ml (at the rate of 2 mg/kg, the volume of solution of 1 ml/kg) for a postoperative caudal analgesia provides adequate anesthesia lower than the ThXII level at most of patients. Children are more senior than 4 years well transfer doses to 3 mg/kg. The volume of the entered solution for epidural introduction at the caudal level can be changed for the purpose of achievement of various prevalence of the touch block that is described in the specialized managements.
Irrespective of anesthesia type, bolyusny introduction of the calculated drug dose is recommended.
Use of drug in concentration is higher than 5 mg/ml, and also intrathecal use of the drug Naropin® for children was not investigated. Use of the drug Naropin® for premature children was not studied.
Application instructions of solution
Solution does not contain preservatives and is intended only for single use. Any amount of the solution which remained in a container after use has to be destroyed.
The opened container with solution has to be autoclaved.
Not opened blister packaging provides sterility of an external surface of a container and is preferable to use in the conditions demanding sterility.

Features of use:

Anesthesia has to be carried out by experienced specialists. Existence of the equipment and medicines for holding resuscitation actions is obligatory. Prior to performance of big blockade the catheter has to be established intravenously.
The personnel providing anesthesia performance have to be appropriately prepared and familiar with diagnosis and treatment of possible side effects, system toxic reactions and other possible complications (see the section "Overdose").
The spinal block with an apnoea and decrease in the ABP can be a complication of inadvertent subarachnoidal introduction. Spasms develop more often at blockade of a brachial plexus and epidural blockade probably owing to accidental intravascular introduction or bystry absorption in the place of an injection.
Performance of blockade of peripheral nerves can demand introduction of large volume of local anesthetic to zones with a large number of vessels, often near large vessels that increases risk of intravascular introduction and/or bystry system absorption that can result in high concentration of drug in plasma.
Some procedures connected using local anesthetics such as injections in the head and a neck, can be followed by the increased frequency of development of serious side effects, regardless of type of the applied local anesthetic. It is necessary to be careful for prevention of an injection to the area of an inflammation.
It is necessary to be careful at administration of drug to patients with blockade of endocardiac conductivity II and III degrees, to patients with a heavy renal failure, to the elderly and weakened patients.
There are messages on exceptional cases of a cardiac standstill at use of the drug Naropin® for epidural anesthesia or blockade of peripheral nerves, especially after accidental intravascular administration of drug, for elderly patients and for patients with the accompanying cardiovascular diseases.
In some cases resuscitation actions were difficult. The cardiac standstill, as a rule, demands longer resuscitation actions.
As Naropin® is metabolized in a liver, it is necessary to show care at use of drug for patients with a serious illness of a liver; in certain cases because of the slowed-down elimination there can be a need of reduction of repeatedly entered anesthetic doses.
Usually at patients with a renal failure at administration of drug once or when using drug during a short span it is not required to adjust a dose. However the acidosis and decrease in concentration of proteins in a blood plasma which are often developing at patients with a chronic renal failure can increase risk of systemic toxic action of drug (see the section "Route of Administration and Doses"). The risk of system toxicity is also increased at use of drug for patients with an underweight of a body and patients with hypovolemic shock.
Epidural anesthesia can lead to decrease in the ABP and bradycardia. Administration of vasoconstrictive drugs or increase in volume of the circulating blood can reduce risk of development of similar side effects. It is necessary to adjust timely decrease in the ABP by intravenous administration of 5-10 mg of ephedrine, if necessary to repeat introduction.
At intra joint administration of drug it is necessary to be careful at suspicion on existence of a recent extensive injury of a joint or surgery with opening of extensive surfaces of a joint, in connection with a possibility of strengthening of absorption of drug and higher concentration of drug in plasma.
The patients receiving therapy by antiarrhytmic drugs III of a class (for example, amiadorony) have to be under careful observation, ECG monitoring in connection with risk of strengthening of cardiovascular effects is recommended.
It is necessary to avoid prolonged use of the drug Naropin® at the patients accepting powerful inhibitors of an isoenzyme CYP1A2 (such as, флувоксамин and эноксацин).
It is necessary to consider a possibility of cross hypersensitivity at simultaneous use of the drug Naropin® with other local anesthetics of amide type.
The patients who are on a diet with sodium restriction need to take into account the content of sodium in drug.
Use of drug for newborns demands the accounting of possible immaturity of bodies and physiological functions of newborns. The clearance of untied fraction of a ropivakain and pipeloksilidin (PPK) depends on body weight and age of the child in the first years of life. Influence of age is expressed in development and a maturity of function of a liver, the clearance reaches the maximum value at the age of about 1-3 years. The elimination half-life of a ropivakain makes 5-6 hours at newborns and children at the age of 1 month in comparison with 3 hours at children of more advanced age. Due to underdevelopment of functions of a liver system exposure of a ropivakain is higher at newborns, is moderate above – at children from 1 to 6 months in comparison with children of more advanced age. The considerable differences in concentration of a ropivakain in a blood plasma of newborns revealed in clinical trials allow to assume the increased risk of emergence of system toxicity in this group of patients, especially at the prolonged epidural infusion.
The recommended doses for newborns are based on limited clinical data.
When using a ropivakain at newborns monitoring of system toxicity (control of signs of toxicity is necessary from the central nervous system, an ECG, blood oxygenation control) and a local neurotoxicity which should be continued after completion of infusion because of slow removal of drug at newborns.
Use of drug in concentration is higher than 5 mg/ml, and also intrathecal use of the drug Naropin® for children was not investigated.
Наропин® it is potentially capable to cause a porphyria and the acute porphyria only in cases can be applied at patients with the diagnosis if there is no safer alternative. In case of hypersensitivity of patients necessary precautionary measures have to be taken.
It was reported about chondrolysis cases at the postoperative prolonged intra joint infusion of local anesthetics. In the majority of the described cases, infusion was carried out to a shoulder joint. Relationship of cause and effect is not established with reception of anesthetics. Наропин® it is not necessary to apply to the prolonged intra joint infusion.
INFLUENCE ON ABILITY TO MANAGE VEHICLES AND OTHER MECHANISMS
In addition to analgeziruyushchy effect, Naropin® can exert weak tranzitorny impact on motive function and coordination. Considering a profile of side effects of drug, it is necessary to be careful at control of vehicles and performance of other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Undesirable reactions to Naropin® are similar to reactions to other local anesthetics of amide type. They should be distinguished from the physiological effects arising because of blockade of sympathetic nerves against the background of epidural anesthesia such as, a lowering of arterial pressure, bradycardia, or the effects connected with technology of administration of drug such as, local injury of a nerve, meningitis, a post-puncture headache, epidural abscess.
From the central and peripheral nervous system
Side effects inherent in local anesthetics
Neuropathy and dysfunction of a spinal cord (syndrome of a front spinal artery, arachnoiditis, syndrome of a horse tail) are possible, are usually connected with technology of carrying out regional anesthesia, but not with effect of drug.
The full spinal block can result from accidental intrathecal introduction of an epidural dose.
Serious complications at system overdose and inadvertent intravascular administration of drug are possible (see the section "Overdose").
Acute system toxicity
Наропин® can cause acute system toxic reactions when using high doses or at bystry increase in its concentration in blood at accidental intravascular administration of drug or its overdose (see the section "Pharmacological Properties" and "Overdose").
The most often found side effects
It was reported about various side effects of drug which vast majority was connected not with influence of the used anesthetic, and with technology of carrying out regional anesthesia.
Most often (> 1%) noted the following side effects which were regarded as whether having clinical value regardless of that relationship of cause and effect was established with anesthetic use: lowering of arterial pressure (ABP) *, nausea, bradycardia, vomiting, paresthesia, fervescence, headache, urination delay, dizziness, fever, increase in arterial pressure, tachycardia, hypesthesia, concern.
Frequency of emergence of undesirable effects is presented as follows:
Very often (> 1/10); Often (> 1/100, <1/10); Infrequently (> 1/1000, <1/100); Seldom (> 1/10 000, <1/1 000); Very seldom (<1/10 000), including separate messages.
Very often
From cardiovascular system: decrease in the ABP *
From the digestive tract (DT): nausea
Often
From a nervous system: paresthesia, dizziness, headache
From cardiovascular system: bradycardia, tachycardia, increase in ADSO of the side of a GIT: vomiting **
From urinogenital system: urination delay
The general: dorsodynia, fever, fervescence
Infrequently
From a nervous system: concern, toxicity symptoms from TsNS (spasms, big convulsive attacks, paresthesias in a circumoral zone, a dysarthtia, numbness of language, a vision disorder, a ring in ears, a hyperacusia, a tremor, muscular spasms), a hypesthesia
From vascular system: syncope
From respiratory system: an asthma, the complicated breath
The general: hypothermia
Seldom
From cardiovascular system: arrhythmia, cardiac standstill
The general: allergic reactions (anaphylactic reactions, Quincke's disease, small tortoiseshell)

* Decrease in the ABP occurs at children often.
** Vomiting occurs at children very often.

Interaction with other medicines:

Summing of toxic effects at co-administration with other local anesthetics or drugs structurally similar to local anesthetics of amide type is possible.
The clearance of a ropivakain decreases to 77% at simultaneous use with fluvoksaminy, the being powerful competitive inhibitor of an isoenzyme of CYP1A2, because of a possibility of similar interaction it is necessary to avoid prolonged use of Naropina® against the background of action of a fluvoksamin.
Increase рН solution above 6,0 can give to formation of precipitated calcium superphosphate because of bad solubility of a ropivakain under existing conditions.
Naropina® solution in plastic infusional bags on the chemical and physical properties is compatible to the following medicines:

Naropin's concentration: 1-2 mg/ml
The added solution                 Concentration
Fentanyl                                      of 1,0 - 10,0 mkg/ml
Morphine                                         of 20,0 - 100,0 mkg/ml

Despite the fact that the received mixes keep chemical and physical stability within 30 days at a temperature not above 30 °C proceeding from data on microbiological purity, it is necessary to use the received mixes of solutions immediately after preparation.

Contraindications:

Hypersensitivity to drug components.
The known hypersensitivity to local anesthetics of amide type.
With care: the weakened elderly patients or patients with serious associated diseases, such as blockade of endocardiac conductivity II and III degrees (sinuatrial, atrioventricular, intra ventricular), the progressing liver diseases, a heavy liver failure, a heavy chronic renal failure, at therapy of hypovolemic shock. For these groups of patients regional anesthesia often is preferable. When carrying out "big" blockade for the purpose of decrease in risk of development of the heavy adverse phenomena it is recommended to optimize previously a condition of the patient, and also to correct an anesthetic dose.
It is necessary to be careful at an injection of local anesthetics in the head and a neck, in connection with the possible increased frequency of development of serious side effects.
At intra joint administration of drug it is necessary to be careful at suspicion on existence of a recent extensive injury of a joint or surgery with opening of extensive surfaces of a joint, in connection with a possibility of strengthening of absorption of drug and higher concentration of drug in plasma.
Special attention should be paid at use of drug for children up to 6 months in connection with immaturity of bodies and functions.
The patients who are on a diet with sodium restriction need to take into account the content of sodium in drug.
USE AT PREGNANCY AND DURING BREASTFEEDING
Pregnancy
Influence of a ropivakain on fertility and reproductive function, and also teratogenic action is not revealed. Researches on assessment of possible action of a ropivakain on fetation at women were not conducted.
Наропин® it is possible to apply at pregnancy only if the expected advantage for mother exceeds potential risk for a fruit (in obstetrics use of drug for anesthesia or an analgesia is well proved).
Researches of influence of drug on reproductive function were conducted on animals. In researches on rats ропивакаин did not exert impact on fertility and a reproduction in two generations. At introduction of the maximum doses of a ropivakain to pregnant rats increase in mortality of posterity in the first three days after the delivery was observed that, perhaps, is explained by toxic effect of a ropivakain on mother,
leading to disturbance of a maternal instinct.
Teratogenecity researches on rabbits and rats did not reveal side effects of a ropivakain on an organogenesis or fetation at early stages. Also during the perinatal and post-natal researches on the rats receiving the most tolerable dose of drug side effects on late stages of fetation, patrimonial activity, a lactation, viability or on growth of posterity were not noted.
Lactation
Allocation of a ropivakain or its metabolites with breast milk was not studied. Proceeding from experimental data, the dose of the drug received by the newborn presumably makes 4% of a dose, the entered mother (concentration of drug in milk / concentration of drug in plasma). The general dose of a ropivakain influencing the child at chest feeding is much less than dose which can get to a fruit at administration of anesthetic of mother at childbirth. In need of use of drug during chest feeding it is necessary to consider a ratio of potential advantage for mother and possible risk for the baby.

Overdose:

Acute system toxicity
At accidental intravascular introduction when carrying out blockade of neuroplexes or other peripheral blockade cases of developing of spasms were observed.
In case of the wrong introduction of an epidural dose of anesthetic emergence of the full spinal block is intratekalno possible.
Accidental intravascular administration of anesthetic can cause immediate toxic reaction.
At overdose during regional anesthesia symptoms of system toxic reaction appear in the delayed order in 15-60 min. after an injection because of slow increase in concentration of local anesthetic in a blood plasma. System toxicity, first of all, is shown by symptoms from the central nervous system (CNS) and cardiovascular system (CCC). These reactions are caused by high concentration of local anesthetic in blood which can arise owing to (accidental) intravascular introduction, overdose or exclusively high adsorption from strongly vaskulyarizirovanny areas.
Reactions from TsNS are similar for all local anesthetics of amide type while reactions from cardiovascular system more depend on the administered drug and its dose.
Central nervous system
Manifestations of system toxicity from the central nervous system develop gradually: at first there are visual disturbances, numbness around a mouth, numbness of language, a hyperacusia, a ring in ears, dizziness. The dysarthtia, a tremor and muscular twitchings are more serious manifestations of system toxicity and can precede emergence of generalized spasms (these signs should not be accepted to neurotic behavior of the patient). When progressing intoxication the loss of consciousness, attacks of spasms lasting from several seconds up to several minutes which are followed by breath disturbance, bystry development of a hypoxia and a hypercapnia because of the increased muscular activity and inadequate ventilation can be observed. In hard cases there can even come the apnoea. The arising acidosis, a hyperpotassemia, a hypocalcemia strengthen toxic effects of anesthetic.
Afterwards, because of redistribution of anesthetic from TsNS and its subsequent metabolism and excretion, there is rather bystry recovery of functions if the high dose of drug was only not entered.
Cardiovascular system
Frustration from cardiovascular system are signs of more serious complications. Decrease in the ABP, bradycardia, arrhythmia and, in some cases, even a cardiac standstill can arise owing to high system concentration of local anesthetics. In rare instances the cardiac standstill is not followed by the previous symptomatology from TsNS. In researches on volunteers intravenous infusion of a ropivakain led to oppression of conductivity and sokratitelny ability of a cardiac muscle. Symptoms from cardiovascular system are usually preceded by manifestations of toxicity from TsNS which can be not noticed if the patient is under the influence of sedatives (benzodiazepines or barbiturates) or under the general anesthesia.
At children it is sometimes more difficult to reveal precursory symptoms of system toxicity of local anesthetics owing to the difficulties experienced by children at the description of symptoms or in case of use of regional anesthesia in combination with the general anesthesia.
Treatment of acute toxicity
At emergence of the first signs of acute system toxicity it is necessary to stop administration of drug immediately.
At emergence of spasms and symptoms of oppression of TsNS sick adequate treatment which purpose is oxygenation maintenance, stopping of spasms, maintenance of activity of cardiovascular system is required. It is necessary to provide oxygenation with oxygen, and if necessary – transition to artificial ventilation of the lungs. If 15-20 seconds of a spasm later do not stop, it is necessary to use anticonvulsants: thiopental of sodium of 1-3 mg/kg in/in (provides bystry stopping of spasms) or diazepam of 0,1 mg/kg in/in (action develops more slowly in comparison with effect of thiopental of sodium). Succinylcholine of 1 mg/kg quickly stops spasms, but at its use the intubation and artificial ventilation of the lungs is required.
At oppression of activity of cardiovascular system (decrease in the ABP, bradycardia) intravenous administration of 5-10 mg of ephedrine is necessary, if necessary in 2-3 min. to repeat introduction. At development of circulator insufficiency or a cardiac standstill it is necessary to begin standard resuscitation actions immediately. It is vital to support optimum oxygenation, ventilation and blood circulation, and also to adjust acidosis. At a cardiac standstill longer resuscitation actions can be required.
At therapy of system toxicity at children it is necessary to adjust doses according to age and body weight of the patient.

Storage conditions:

To store at a temperature not above 30 °C. Not to freeze. To store in the places unavailable to children. Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for injections of 2 mg/ml, 7,5 mg/ml and 10 mg/ml.
Solution for injections of 2 mg/ml
On 20 ml in the soldered ampoules from polypropylene. Each ampoule is placed in a blister strip packaging. 5 blister strip packagings with the application instruction in a cardboard pack with control of the first opening.:
On 100 ml or 200 ml in polypropylene containers (bags) corked by a butylrubber stopper and a leaflike aluminum plate. Polypropylene containers (bags) are individually packed into a blister strip packaging from polypropylene/paper. On 5 blister strip packagings in a cardboard pack with the application instruction.
On 10 ml in the soldered ampoules from polypropylene. Each ampoule is placed in a blister strip packaging. 5 blister strip packagings with the application instruction in a cardboard pack with control of the first opening.
Solution for injections of 7,5 mg/ml and 10 mg/ml.