Instruction for use: Levobupivacainum

Latin name:Levobupivacaine (genus.Levobupivacaini)

Chemical name

(2S) -1-butyl-N- (2,6-dimethylphenyl) piperidine-2-carboxamide

Gross formula

C18H28N2O

Pharmacological group of substance Levobupivacainum

Local Anesthetics

The nosological classification (ICD-10)

O80.9 Single-issue spontaneous delivery, unspecified: Childbirth

R52.9 Unspecified pain: Pain after cholecystectomy; Pain shooting; Non-malignant pain syndrome; Obstetric and gynecological pain; Pain syndrome; Pain syndrome in the postoperative period; Pain syndrome in the postoperative period after orthopedic operations; Painful syndrome of inflammatory genesis; Pain syndrome of non-oncological genesis; Pain syndrome after diagnostic procedures; Pain syndrome after the diagnostic intervention; Pain syndrome after operations; Pain syndrome after surgery; Pain syndrome after orthopedic surgery; Pain syndrome after trauma; Pain syndrome after removal of hemorrhoids; Pain syndrome after surgery; Pain syndrome with inflammation of non-rheumatic nature; Pain syndrome with inflammatory lesions of the peripheral nervous system; Pain syndrome in diabetic neuropathy; Pain syndrome in acute inflammatory diseases of the musculoskeletal system; Pain syndrome in the pathology of tendons; Pain syndrome with smooth muscle spasms; Pain syndrome with smooth muscle spasms (renal and biliary colic, intestinal spasm, dysmenorrhea); Pain syndrome with spasms of smooth muscles of internal organs; Pain syndrome with spasms of smooth muscles of internal organs (renal and biliary colic, intestinal spasm, dysmenorrhea); Pain syndrome with injuries; Pain syndrome with injuries and after surgical interventions; Pain syndrome in chronic inflammatory diseases of the musculoskeletal system; Pain syndrome with duodenal ulcer; Pain syndrome with peptic ulcer disease; Pain syndrome with peptic ulcer of stomach and duodenum; Painful sensations; Pain during menstruation; Pain syndromes; Painful conditions; Painful leg fatigue; Gum pain when wearing dentures; The pain of exit points of cranial nerves; Painful irregular menstruation; Painful dressings; Painful muscular spasm; Painful growth of teeth; Pain; Pain in lower limbs; Pain in the area of the operating wound; Pain in the postoperative period; Pain in the body; Pain after diagnostic interventions; Pain after orthopedic surgery; Pain after surgery; Pain in the flu; Pain in diabetic polyneuropathy; Pain in burns; Pain in intercourse; Pain during diagnostic procedures; Pain during therapeutic procedures; Pain for colds; Pain with sinusitis; Pain in case of injury; Pain of a traumatic nature; Pain in the postoperative period; Pain after Diagnostic Interventions; Pain after sclerosing therapy; Pain after surgery; Postoperative pain; Postoperative and post-traumatic pain; Post-traumatic pain; Pain when swallowing; Pain in infectious inflammatory diseases of the upper respiratory tract; Pain with burns; Pain with traumatic muscle damage; Pain in case of injury; Pain when extracting a tooth; Pain of traumatic origin; Pain caused by spasm of smooth muscles; Severe pain syndrome; Severe pain syndrome of traumatic origin; Postoperative pain; Postoperative pain syndrome; Post-traumatic pain; Post-traumatic pain syndrome; Torpid pain syndrome; Traumatic pain; Moderate pain; Moderately expressed pain syndrome; Moderate pain syndrome; Polyartralgia in polymyositis

Z100.0 * Anesthesiology and premedication: Abdominal surgery; Adenomectomy; Amputation; Angioplasty of the coronary arteries; Carotid artery angioplasty; Antiseptic treatment of skin in wounds; Antiseptic treatment of hands; Appendectomy; Atheroctomy; Balloon coronary angioplasty; Vaginal hysterectomy; Venous bypass; Interventions on the vagina and cervix; Interventions on the bladder; Interference in the oral cavity; Reconstructive-reconstructive operations; Hand hygiene of medical personnel; Gynecological Surgery; Gynecological interventions; Gynecological operations; Hypovolemic shock during surgery; Disinfection of purulent wounds; Disinfection of the edges of wounds; Diagnostic Interventions; Diagnostic procedures; Diathermocoagulation of the cervix; Long-term surgeries; Replacement of fistulous catheters; Infection in orthopedic surgical interventions; Artificial heart valve; Kistectomy; Short-term outpatient surgery; Short-term operations; Short-term surgical procedures; Cryotyreotomy; Blood loss during surgical interventions; Bleeding during surgery and in the postoperative period; Kuldotsentez; Laser coagulation; Laserocoagulation; Laser retinopathy of the retina; Laparoscopy; Laparoscopy in gynecology; Likvornaya fistula; Small gynecological operations; Small surgical interventions; Mastectomy and subsequent plastic surgery; Mediastinotomy; Microsurgical operations on the ear; Mukinging operations; Suturing; Minor surgery; Neurosurgical operation; Eclipse of the eyeball in ophthalmic surgery Orchiectomy; Pancreatectomy; Pericardectomy; The rehabilitation period after surgical operations; Reconvalence after surgical intervention; Percutaneous transluminal coronary angioplasty; Pleural Thoracocentesis; Pneumonia postoperative and post traumatic; Preparing for surgical procedures; Preparing for a surgical operation; Preparation of the surgeon's arms before surgery; Preparation of the colon for surgical interventions; Postoperative aspiration pneumonia in neurosurgical and thoracic operations; Postoperative nausea; Postoperative hemorrhage; Postoperative granuloma; Postoperative shock; Early postoperative period; Myocardial revascularization; Resection of the apex of the tooth root; Resection of the stomach; Bowel resection; Resection of the uterus; Liver resection; Small bowel resection; Resection of a part of the stomach; Reocclusion of the operated vessel; Gluing of tissues during surgical interventions; Suture removal; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity;Condition after gastrectomy; Condition after resection of the small intestine; Condition after tonsillectomy; Condition after removal of duodenum; Condition after phlebectomy; Vascular Surgery; Splenectomy; Sterilization of surgical instrument; Sterilization of surgical instruments; Sternotomy; Dental surgery; Dental intervention on periodontal tissues; Strumectomy; Tonsillectomy; Thoracic surgery; Total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinectomy; Removal of a tooth; Cataract removal; Removing Cysts; Removal of tonsils; Removal of myoma; Removal of mobile milk teeth; Removal of polyps; Removal of a broken tooth; Removal of the uterus; Removal of seams; Urethrotomy; Fistula of the luminal ducts; Frontoetmoidohaimorotomy; Surgical infection; Surgical treatment of chronic ulcers of extremities; Surgery; Surgery in the anus; Surgery on the large intestine; Surgical practice; Surgical procedure; Surgical interventions; Surgical interventions on the digestive tract; Surgical interventions on the urinary tract;Surgical interventions on the urinary system; Surgical interventions on the genitourinary system; Surgical intervention on the heart; Surgical procedures; Surgical operations; Surgical operations on veins; Surgical intervention; Vascular; Cholecystectomy; Partial resection of the stomach; Extraperitoneal hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass grafting; Extirpation of the tooth; Extirpation of infant teeth; Extirpation of pulp; Extracorporeal circulation; Extraction of the tooth; Extraction of teeth; Extraction of cataracts; Electrocoagulation; Endourological interventions; Episiotomy; Ethmoidotomy; Complications after tooth extraction

CAS code

27262-47-1

Pharmacology

Pharmacodynamics

Levobupivacaine is a local anesthetic and long-acting analgesic. The agent blocks the transfer of impulses in sensory and motor nerve fibers mainly due to the effect on the potential-dependent sodium channels of the cell membrane, although it also causes blockade of the potassium and calcium channels. In addition, levobupivacaine interferes with the transfer and conduct of impulses in other tissues: the most important role in the development of clinical adverse reactions is its effect on the CVS and CNS.

In studies of clinical pharmacology using the ulnar blockade model, it was demonstrated that levobupivacaine has the same clinical effect as bupivacaine.

Data on the safety of levobupivacaine when administered for more than 24 h are limited.

Pharmacokinetics

Distribution. In clinical studies in humans, it has been shown that the distribution of levobupivacaine after intravenous administration is basically the same as that of bupivacaine. The concentration of levobupivacaine in the blood plasma depends on the dose and route of administration, since the absorption of tissue from the site of administration is influenced by its vascularization.

In vitro studies have shown that the binding of levobupivacaine to plasma proteins in humans is> 97% at concentrations of 0.1 to 10 μg / ml.

In clinical pharmacology studies with iv administration of 40 mg of levobupivacaine, the mean T1 / 2 was approximately 80 ± 22 min, Cmax - (1.4 ± 0.2) μg / ml and AUC - (70 ± 27) μg · min / ml.

Epidural administration of 75 mg (0.5%) and 112.5 mg (0.75%) of levobupivacaine, and brachial plexus blocking with levobupivacaine at a dose of 1 mg / kg (0.25%) and 2 mg / kg (0 , 5%), the mean Cmax and AUC0-24 are approximately proportional to the administered dose. After epidural administration of 112.5 mg (0.75%) of levobupivacaine, the mean Cmax and AUC values are 0.58 μg / ml and 3.56 μg / h / ml, respectively.

Vd after IV introduction is 67 liters.

Metabolism. Levobupivacaine is largely metabolized, in urine and feces, unchanged levobupivacaine is not detected. The main metabolite of levobupivacaine - 3-hydroxylevepupivacaine - is secreted into the urine in the form of conjugates with glucuronic acid and sulfate ester. In vitro studies, it has been shown that cytochrome CYP3A4 and CYP1A2 isoenzymes participate in the metabolism of levobupivacaine, with the formation of disbutyllum bupivacaine and 3-hydroxylevepupivacaine, respectively. These studies have shown that the metabolism of levobupivacaine and bupivacaine is similar.

Ratsemizatsii levobupivakina in vivo is not revealed.

Excretion. After iv introduction, levobupivacaine is excreted on average for 48 hours at 95%, with 71% excreted through the kidneys, 24% through the intestine.

When administered as an IV infusion, the total plasma clearance of levobupivacaine is 39 l / h, and the final T1 / 2 is 1.3 hours.

Special patient groups

Violation of the function of the liver. Data on the pharmacokinetics of levobupivacaine in patients with impaired liver function are not available (see "Precautions").

Impaired renal function. There are no data on the pharmacokinetics of levobupivacaine in patients with impaired renal function. Levobupivacaine is largely metabolized, unchanged in the urine is not detected.

Application ofthe Levobupivacaine

Adults

Anesthesia during surgical interventions:

- for large surgical interventions, for example epidural (including anesthesia during cesarean section), intrathecal, blockade of peripheral nerves;

- with small surgical interventions, for example infiltration anesthesia, peribulbar blockade (in eye surgery).

Pain relief: prolonged epidural infusion, single or multiple bolus epidural administration to relieve pain, especially during the postoperative period or during childbirth.

Children

Anesthesia: ilio-inguinal and ilio-hypogastric blockade.

Contraindications

General contraindications to regional anesthesia, hypersensitivity to levobupivacaine, as well as to local anesthetic drugs of the amide group, intravenous regional anesthesia (Biru blockade), a significant reduction in blood pressure (for example, in cardiogenic or hypovolemic shock), paracervical blockade in obstetric practice. "Application in pregnancy and lactation").

The dosage of 7.5 mg / ml is contraindicated in obstetric practice because of the increased risk of cardiotoxicity when bupivacaine is administered.

Restrictions on the use

Administration of levobupivacaine for> 24 h; in patients receiving antiarrhythmic drugs with the properties of local anesthetics (mexiletine) and antiarrhythmic drugs of class III (with the application of the latter may develop additive toxic effects); regional anesthesia in patients with cardiovascular diseases, in particular with severe heart rhythm disorders; in patients with previous CNS diseases; in patients receiving other local anesthetics or drugs similar in structure to local anesthetics of the amide type; in patients with liver disease or a decrease in hepatic blood flow (for example, with cirrhosis or alcoholic liver disease).

Application in pregnancy and lactation

Levobupivacaine can not be used for paracervical blockade in pregnant women. Given the cases of bradycardia in the fetus with the introduction of bupivacaine, it is impossible to exclude the same action of levobupivacaine.

There are no clinical data on the use of levobupivacaine in the first trimester of pregnancy. In studies on animals teratogenic action of levobupivacaine was not recorded. At the same time, at the systemic exposure level of levobupivacaine, which is achieved in clinical practice in humans, embryotoxic effects were recorded in animals. The potential risk to humans is unknown. Thus, in the absence of an explicit need for women in the first trimester of pregnancy, levobupivacaine should not be given.

Currently, there is extensive experience with the use of bupivacaine in obstetric surgical interventions (during pregnancy and delivery), with no embryotoxic effect of bupivacaine. The dosage of 7.5 mg / ml is contraindicated in obstetric practice because of the increased risk of cardiotoxicity when bupivacaine is administered.

Information about whether levobupivacaine penetrates into breast milk does not. However, levobupivacaine appears to be less lactate than bupivacaine. Breastfeeding is possible after local anesthesia.

Side effects of Levobupivacainum

Undesirable reactions to levobupivacaine are consistent with those in the use of drugs of this class. The most frequent adverse reactions are a decrease in blood pressure, nausea, anemia, vomiting, dizziness, headache, fever, pain during the procedure, back pain and fetal distress syndrome (when used in obstetric practice).

Undesirable reactions recorded in clinical studies and post-registration observations are given in accordance with organ and organ damage and frequency of occurrence: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); It is not known (based on the available data, it is impossible to estimate the frequency).

On the part of the blood and lymphatic system: very often - anemia.

From the side of the immune system: unknown - allergic reactions (in serious cases - anaphylactic shock), hypersensitivity.

From the nervous system: often - dizziness, headache; unknown - convulsions, loss of consciousness, drowsiness, syncope, paresthesia, paraplegia, paralysis1.

From the side of the organ of vision: unknown - blurred vision, ptosis2, mioz2, enophthalmus2.

Cardiac disorders: unknown - AV blockade, cardiac arrest, ventricular tachyarrhythmias, tachycardia, bradycardia.

From the side of the vessels: very often - a decrease in blood pressure; unknown - hyperemia2.

On the part of the respiratory system, chest and mediastinal organs: unknown - stopping breathing, laryngeal edema, apnea, sneezing.

From the digestive tract: very often - nausea; often - vomiting; unknown - hypoesthesia of the oral mucosa, a violation of sphincter function control1.

From the skin and subcutaneous tissues: unknown - angioedema, urticaria, pruritus, hyperhidrosis, anhidrosis2, erythema.

From the musculoskeletal system and connective tissue: often - back pain; unknown - muscle twitching, muscle weakness.

From the side of the kidneys and urinary tract: unknown - dysfunction of the bladder.

Pregnancy, postpartum and perinatal conditions: often - distress syndrome of the fetus.

From the genitals and the mammary gland: unknown - priapism1.

General disorders and disorders at the injection site: often - increased body temperature.

Laboratory and instrumental data: unknown - decrease in cardiac output, changes in ECG.

Injury, intoxication and manipulation imbalance: often - pain during the procedure.

1 May be a symptom or sign of horse tail syndrome.

2 May be a symptom or sign of transient Horner's syndrome.

With the use of local anesthetics, unwanted reactions rarely develop, but they can occur with an overdose or accidental intravascular injection, while being serious.

Cases of cross-sensitivity to various anesthetic agents of the amide group are described.

The occasional intrathecal administration of levobupivacaine can lead to spinal anesthesia at a very high level.

The effect of levobupivacaine on CVS is associated with a decrease in conduction, excitability and contractility of the myocardium. This is usually preceded by signs of toxic CNS damage, such as convulsions, at the same time in rare cases, cardiac arrest occurs without any prodromal neurologic symptoms.

The defeat of the nervous system is a rare but well-diagnosed complication of regional, in particular epidural and spinal, anesthesia. It can be associated with direct damage to the spinal cord or spinal nerves, the syndrome of the anterior cerebrospinal artery, the introduction of an irritant or an unsterile solution. In rare cases, changes are kept constantly.

There is evidence of continued weakness or sensory disturbances associated with the administration of levobupivacaine. Sometimes these phenomena can be permanent. It is difficult to determine whether such long-term effects occur due to toxic effects or are signs of undiagnosed traumatic injury during surgery, or when other mechanical factors, in particular catheter placement and manipulation, are influenced.

There are reports of the development of ponytail syndrome or the appearance of symptoms and signs of possible damage to the base of the spinal cord or roots of the spinal nerves (including weakness of the lower extremities, paresthesia or paralysis, loss of control of bowel movement and / or urination and priapism) associated with levobupivacaine therapy. With the introduction of levobupivacaine for more than 24 hours, these phenomena were more severe and in some cases did not completely disappear (see "Precautions").

However, it is impossible to determine whether these phenomena were associated with the action of levobupivacaine, a mechanical trauma of the spinal cord or roots of the spinal nerves, or the collection of blood in the region of the base of the spine.

Also, rare cases of transient Horner's syndrome (ptosis, miosis, enofthalm, unilateral sweating and / or hyperemia) associated with the use of local anesthetics, including levobupivacaine, are described. After discontinuing therapy, these phenomena disappear.

Interaction

In vitro studies have shown that cytochrome P450 isoenzymes CYP3A4 and CYP1A2 are involved in the metabolism of levobupivacaine. The conversion of levobupivacaine may be affected by inhibitors of the isoenzyme CYP3A4 (in particular ketoconazole) and CYP1A2 (eg, methylxanthines), although clinical studies of such interactions have not been conducted.

Levobupivacaine should be used with caution in patients receiving antiarrhythmic drugs with the properties of local anesthetics (mexiletine) and antiarrhythmic drugs of class III (with the application of the latter may develop additive toxic effects).

Clinical studies evaluating the effect of levobupivacaine in combination with epinephrine have not been conducted.

Overdose

After a random intravascular injection of a local anesthetic, an immediate toxic reaction may occur. In case of an overdose of levobupivacaine, Cmax is reached only 2 hours after the injection (depending on the injection site), so the symptoms of toxic damage can be delayed. It is possible to extend its effect.

Systemic adverse reactions following an overdose or unintentional intravascular injection of a local long-acting anesthetic include symptoms of CCC and CNS damage.

Impact on CNC. With the development of seizures, immediately enter / in sodium thiopental or diazepam, titrating the dose accordingly. Thiopental sodium and diazepam can also have an inhibitory effect on the central nervous system, respiratory and cardiovascular activities. Thus, with the introduction of these drugs, apnea can develop. Drugs that block neuromuscular transmission should be used only if there is the possibility of maintaining airway patency and treating the patient with complete muscle relaxation.

In the absence of timely treatment, seizures, subsequent hypoxia and hypercapnia, as well as depression of cardiac activity under the influence of local anesthetics can cause heart rhythm disturbances, ventricular fibrillation and cardiac arrest.

Impact on CAS. Preliminary introduction of liquid and / or use of vasopressors allows to prevent or reduce the decrease in blood pressure. With a decrease in blood pressure, IV infusion of crystalloids and colloids and / or vasopressor administration in increasing doses (eg, ephedrine 5-10 mg) is indicated. Also, as soon as possible, eliminate all other causes of blood pressure lowering.

With the development of severe bradycardia, it is advisable to administer atropine in a dose of 0.3-1 mg, which allows to increase the heart rate to acceptable values. If heart rhythm disturbances occur, appropriate treatment should be performed, ventricular fibrillation requires emergency cardioversion.

Routes of administration

Injectively.

Precautions for the substance Levobupivacainum

All types of local or regional anesthesia should be performed in a well-equipped health facility, staff should have experience of regional anesthesia, and be able to diagnose possible adverse reactions and appropriate treatment.

Levobupivacaine can cause allergic reactions, violations of the CAS and neurological disorders.

In patients with cardiovascular diseases, in particular with severe heart rhythm disorders, regional anesthesia with levobupivacaine should be conducted with caution.

In patients with previous CNS diseases, the ingestion of a local anesthetic in the CNS with epidural administration may lead to an aggravation of these diseases. Therefore, when planning epidural anesthesia in these patients it is necessary to conduct an appropriate clinical evaluation.

Epidural anesthesia. Concentrated solution of levobupivacaine (0.5-0.75%) with epidural anesthesia should be administered fractional by 3-5 ml, gradually increasing the dose, with the interval between administrations should be sufficient in order to have time to determine the toxic manifestations in the case of drugs in the case lumen of the vessel or intrathecally.

Cases of severe bradycardia, lowering blood pressure and respiratory failure with cardiac arrest during the use of local anesthetics have been described (some of these cases ended in a fatal outcome). If you need a large dose of levobupivacaine, for example, with epidural blockade, it is recommended to enter a preliminary test dose with 3-5 ml of lidocaine with epinephrine. Unintentional entry of levobupivacaine into the vascular bed can be detected by a temporary increase in heart rate, and accidental ingestion of it into the subsatellite space - according to the symptoms of the spinal blockade. With prolonged (intermittent) administration of levobupivacaine through a catheter, an aspiration test (before the first and each subsequent additional injection) should be performed. Levobupivacaine is allowed to enter the vessel even if there is no blood in the syringe during the aspiration test. When performing epidural anesthesia, it is recommended first to enter a test dose and monitor the action of levobupivacaine before the entire dose is administered.

Any local anesthetic for epidural administration can cause a decrease in blood pressure and a bradycardia. In this regard, all patients should be provided with venous access. It is also necessary to ensure the availability of appropriate solutions, vasopressors, anesthetics with anticonvulsant action, muscle relaxants, atropine and equipment for resuscitation (see Overdose).

Epidural analgesia. There are post-registration data on the development of horse tail syndrome and the appearance of signs of neurotoxicity (see "Side effects") that have been associated with the administration of levobupivacaine in time for the purpose of epidural analgesia for 24 hours or more. With the infusion of levobupivacaine> 24 h, such phenomena were more severe, in some cases after them residual effects persisted. In this regard, the introduction of levobupivacainum for> 24 hours should be carried out very carefully and only when the benefit to the patient significantly exceeds the risk.

With the administration of any local anesthetic, it is necessary to perform blood or cerebrospinal fluid aspiration (when necessary) before the injection of the main and each subsequent dose to avoid drug exposure to the lumen of the vessel or intrathecal. However, a negative aspiration test does not guarantee against the entry of drugs into the vascular bed or subshell. In patients receiving other local anesthetics or drugs similar in structure to local anesthetics of the amide type, levobupivacainum should be used with caution because of the additive toxic effect of these drugs.

Regional blockade of large nerve trunks. In order to provide functional venous access, the patient must receive IV fluid through a permanent catheter. To ensure that a high concentration of levobupivacaine is not produced in the blood plasma and serious unwanted reactions do not develop, the lowest dose should be used to achieve effective anesthesia. You can not inject large amounts of anesthetic with high speed, if possible, levobupivacainum should be injected fractionally, gradually increasing the dose.

Local anesthesia in the head and neck area. The administration of even small doses of levobupivacainum to the head and neck area (with retrobulbar blockade, blockade during dental interventions and blockade of the stellate ganglion) can cause severe undesirable reactions similar to those in systemic toxic effects after a random intravascular injection in a larger dose. The introduction of levobupivacainum requires extreme caution.

It is possible to develop reactions caused by intravenous injection of an anesthetic and its entry into the cerebral bloodstream by a retrograde route. Undesirable reactions can also be associated with puncture of the optic nerve dura during retrobulbar blockade with the diffusion of some local anesthetic through the subdural space into the midbrain. It is necessary to carry out constant monitoring and careful monitoring of the parameters of respiratory and cardiac activity in patients to whom these blockades are performed. Also, equipment for resuscitation and staff with appropriate training should be available.

Application in surgical ophthalmology. Specialists who perform a retrobulbar blockade should remember the possibility of developing a stoppage of breathing with local administration of an anesthetic. As with other variants of regional anesthesia, before the retrobulbar blockade is carried out, it is necessary to make sure that equipment, personnel and drugs are available to treat disorders such as respiratory depression or arrest, convulsions, agitation or suppression of cardiac activity. As in the case of other types of anesthesia, after retrobulbar blockade, constant monitoring is necessary to monitor the described adverse reactions.

Special patient groups

Use in weakened and elderly patients, as well as patients with acute diseases. Levobupivacainum in attenuated and elderly patients, as well as patients with acute diseases should be used with caution.

Violation of the function of the liver. Since levobupivacaine is metabolized in the liver, patients with liver disease or with a decrease in hepatic blood flow (for example, with cirrhosis or alcoholic liver disease), levobupivacaine should be administered with caution (see "Restrictions on Use").

Influence on ability to drive vehicles and work with mechanisms. Levobupivacainum can have a significant effect on the ability to drive vehicles and work with mechanisms. It is necessary to warn patients about inadmissibility of management of vehicles and work with mechanisms before the resolution of all the effects of anesthesia and immediate effects of surgical intervention.