Longocaine® hevi

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LONGOKAIN® HEAVY (LONGOKAIN® HEAVY)

Composition:

Active substance: bupivacaine;

1 ml of solution contains 5 mg of anhydrous bupivacaine hydrochloride;

Excipients: glucose monohydrate, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: transparent colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Local anesthetics. Amides. Bupivacaine.

ATC code N01B B01.

Pharmacological Properties.

Pharmacodynamics.

Longocaine® Heavy contains bupivacaine – a long-acting amide-type local anesthetic. Bupivacaine reversibly blocks impulse conduction along nerve fibers by inhibiting sodium ion transport across nerve membranes. Similar effects may also occur at excitable membranes of the brain and myocardium.

Longocaine® Heavy is intended for hyperbaric spinal anesthesia. The relative density of the injection solution at 20 °C is 1.026 (equivalent to 1.021 at 37 °C). Gravity significantly influences the initial distribution of Longocaine® Heavy in the subarachnoid space.

Pharmacokinetics.

Bupivacaine is a lipophilic drug with an oil/water partition coefficient of 27.5. Absorption occurs in two phases. The elimination half-lives are approximately 50 minutes and 400 minutes, respectively. The slow absorption phase is the rate-limiting factor for bupivacaine elimination, explaining why the terminal elimination half-life is longer after subarachnoid administration compared to intravenous administration. Blood concentrations of bupivacaine following intrathecal administration are significantly lower than with other regional anesthetic techniques. This is due to the small dose required for intrathecal anesthesia. Overall, the increase in maximum plasma concentration is about 0.4 mg/L for every 100 mg administered. This means that after administration of 20 mL of solution, plasma concentrations will reach 0.1 mg/L.

After intravenous administration, the total plasma clearance of bupivacaine is 0.58 L/min, the steady-state volume of distribution is 73 L, the terminal elimination half-life is 2.7 hours, and the hepatic extraction ratio is 0.4. Bupivacaine is primarily bound to α1-acid glycoprotein, with protein binding in blood amounting to 96%. Bupivacaine is metabolized in the liver. Its clearance depends more on changes in hepatic intracellular enzymes than on liver perfusion. The metabolites are also pharmacologically active, but to a much lesser extent than bupivacaine.

Bupivacaine crosses the placental barrier. Free bupivacaine concentrations are equal in mother and fetus. However, total plasma concentration is lower in the fetus, which has a lower degree of protein binding.

Clinical characteristics.

Indications.

Indicated for intrathecal (subarachnoid) spinal anesthesia in surgery in adults and children of various ages (urological and lower limb surgeries lasting 2-3 hours, as well as abdominal surgeries lasting 45-60 minutes).

Contraindications.

Hypersensitivity to amide-type local anesthetics or to any component of the drug.

Intrathecal anesthesia, regardless of the local anesthetic used, has its own contraindications, including:

• active diseases of the central nervous system, such as meningitis, poliomyelitis, intracranial hemorrhage, subacute combined degeneration of the spinal cord due to pernicious anemia, and tumors of the brain and spinal cord;
• spinal canal stenosis and active-stage diseases (e.g., spondylitis, tuberculosis, tumors) or recent spinal trauma (e.g., fracture);
• sepsis;
• purulent skin infection at or near the lumbar puncture site;
• cardiogenic or hypovolemic shock;
• coagulation disorders or ongoing anticoagulant therapy.

Interaction with other medicinal products and other types of interactions.

Bupivacaine should be administered with caution to patients receiving local anesthetics or drugs structurally related to amide anesthetics, such as lidocaine or mexiletine, as the risk of additive toxic effects increases. Specific studies on the interaction of bupivacaine with Class III antiarrhythmic agents (e.g., amiodarone) have not been conducted, but caution is advised if concomitant administration of these drugs is necessary.

Special precautions for use.

Spinal anesthesia must be administered by a physician with adequate knowledge and experience.

Procedures involving regional anesthetics should be performed in departments equipped with equipment for artificial ventilation of the lungs. Equipment for emergency resuscitation and appropriate medications must be readily available for immediate use.

Before initiating spinal anesthesia, provision should be made for intravenous access, such as intravenous infusion. The physician responsible for administering anesthesia must take necessary precautions to avoid intravascular injection of the drug and must be adequately trained and familiar with the diagnosis and treatment of adverse effects, systemic toxicity, and other complications. If signs of acute systemic toxicity or total spinal block occur, administration of the local anesthetic must be stopped immediately.

Like all local anesthetics, bupivacaine may cause acute toxic effects on the central nervous and cardiovascular systems when high plasma concentrations are achieved, particularly following accidental intravascular injection or injection into highly vascularized areas.

Cases of ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse, and fatal outcomes have been reported in association with high systemic concentrations of bupivacaine. In cases of cardiac arrest, prolonged resuscitation efforts may be required to achieve a successful outcome. High systemic concentrations are not expected with doses typically used for spinal anesthesia.

Elderly patients and those in late stages of pregnancy are at increased risk of developing extensive or total spinal block, which may lead to depression of cardiovascular and respiratory function. Therefore, the dose of the drug should be reduced in these patients.

Spinal anesthesia with any local anesthetic may result in arterial hypotension and bradycardia. These effects should be anticipated, and appropriate preventive measures should be taken, which may include preloading with a crystalloid or colloid solution. In the event of arterial hypotension, a vasopressor agent such as ephedrine 10–15 mg should be administered intravenously. Severe arterial hypotension may occur due to hypovolemia from hemorrhage or dehydration, or aortocaval compression in patients with massive ascites, large intra-abdominal tumors, or in late pregnancy. Significant arterial hypotension should be avoided in patients with cardiac decompensation.

Sudden and severe arterial hypotension may develop during spinal anesthesia in patients with hypovolemia from any cause.

Spinal anesthesia may cause paralysis of intercostal muscles, and patients with pleural effusion may experience respiratory insufficiency. Sepsis may increase the risk of developing a postoperative intraspinal abscess.

Neurological injuries are rare complications of spinal anesthesia and may result in paresthesia, anesthesia, motor weakness, and paralysis. These effects may occasionally be long-lasting.

Before initiating treatment, it should be considered that the benefits of treatment must outweigh the potential risks to the patient.

Patients with poor general health due to age or other compromising factors, such as partial or complete heart conduction block, or progressive hepatic or renal dysfunction, require special attention, although conduction anesthesia may be the optimal choice for surgical procedures in these patients.

Patients receiving class III antiarrhythmic drugs (e.g., amiodarone) should be closely monitored. In addition, ECG monitoring should be considered, as the cardiologic effects of these drugs may be additive.

Use during pregnancy or breastfeeding.

Pregnancy

There is no evidence of adverse effects of the drug on human pregnancy.

There is evidence of reduced fetal survival in rats and embryological effects in rabbits following administration of Longocaine® Heavy at high doses during pregnancy. Therefore, Longocaine® Heavy should not be used in early pregnancy except when the expected benefits outweigh the potential risks.

It should be noted that the dose of the drug should be reduced in patients in late stages of pregnancy.

Breastfeeding

Bupivacaine passes into breast milk, but in such low amounts that, generally, there is no risk to the infant when therapeutic doses of the drug are administered.

Ability to affect reaction speed when driving or operating machinery.

In addition to the direct effects of anesthetics, local anesthetics may have a minimal effect on mental function and motor coordination, even in the absence of overt central nervous system toxicity, and may also cause temporary impairment of motor activity and alertness.

Method of Administration and Dosage

Bupivacaine is a long-acting amide-type local anesthetic. Longocaine® Heavy has a rapid onset and prolonged duration of action. The duration of analgesia at spinal segments T10–T12 is
2–3 hours.

Administration of Longocaine® Heavy results in moderate muscle relaxation of the lower limbs lasting 2–2.5 hours. The blockade of abdominal muscle contractility facilitates the use of the solution for abdominal surgical procedures lasting 45–60 minutes. The duration of muscle contractility blockade does not exceed the duration of analgesia. The effect of Longocaine® Heavy on the cardiovascular system is similar to or less pronounced than the effects observed with other agents used for spinal anesthesia.

Method of administration for intrathecal use.

Adults and children aged 12 years and older

The recommended doses listed below should be considered as guidelines for administering the drug to average adult patients.

The figures indicate the expected range of average effective doses. In the presence of factors affecting specific blockade techniques or to meet individual patient requirements, standard dosage recommendations should be taken into account.

The physician’s experience and the patient’s physical condition are important factors in determining the required dose. The lowest effective dose necessary to achieve adequate anesthesia should be used. Individual variability may occur at the onset and during anesthesia, and the extent of anesthetic spread may be difficult to predict, although it depends on the volume of the administered drug.

Dosage recommendations

Intrathecal anesthesia in surgery:

2–4 mL (10–20 mg of bupivacaine hydrochloride).

The dose should be reduced in elderly patients and in pregnant women in late stages of pregnancy.

Neonates, infants, and children with body weight up to 40 kg

Longocaine® Heavy may be used in pediatric practice.

One of the differences between children and adults is the relatively larger volume of cerebrospinal fluid in neonates and infants, which necessitates the use of a relatively higher dose per kg of body weight to achieve the same level of blockade as in adults.

Regional anesthesia procedures in children should be performed by qualified physicians experienced in pediatric regional anesthesia and in the administration of this anesthetic technique.

The doses listed in Table 1 should be considered as guidelines when using the drug in pediatric patients. Individual variability has been observed. Standard dosage recommendations should be considered in the presence of factors affecting specific blockade techniques and to meet individual patient needs.

The lowest effective dose required to achieve adequate anesthesia should be used.

Table 1

Dosage recommendations for neonates, infants, and children

The distribution of the drug during anesthesia achieved with the use of Longocaine® Hevy depends on several factors, including the volume of the solution and the patient's position during and after injection.

When 3 mL of Longocaine® Hevy medicinal product is administered into the L3-L4 intervertebral space of a patient sitting upright, the drug spreads to the spinal cord segments T7-T10. In a patient receiving the injection while lying horizontally and then assuming the supine position, the block extends to the spinal cord segments T4-T7. It should be noted that the level of spinal anesthesia achieved after administration of any local anesthetic may be unpredictable in an individual patient.

The recommended injection site is located below L3.

The effect of Longocaine® Hevy administered by injection in doses exceeding 4 mL has not been studied to date; therefore, such volumes are not recommended.

The solution should be used as soon as possible after the ampoule has been opened. Any unused solution should be discarded.

Children.

Longocaine® Hevy can be used in pediatric practice. For further information, see section "Dosage and method of administration".

Overdose.

It is unlikely that administration of Longocaine® Hevy at recommended doses would result in high plasma concentrations leading to systemic toxicity. However, systemic toxic reactions may occur when the drug is used concomitantly with other local anesthetics, as toxic effects are additive.

Adverse reactions.

The adverse reaction profile observed with Longocaine® Heavy is similar to that of other long-acting local anesthetics used for intrathecal anesthesia.

Table 2

Adverse reactions occurring during administration of the drug

Adverse reactions caused by the drug itself are difficult to distinguish from physiological effects associated with blockade of nerve fibers (e.g., decreased blood pressure, bradycardia, temporary urinary retention), conditions directly caused by the procedure (e.g., spinal hematoma), or indirectly by needle puncture (e.g., meningitis, epidural abscess), or conditions related to cerebrospinal fluid leakage (e.g., post-dural puncture headache).

Acute systemic toxicity

It is unlikely that the use of Longocaine® Heavy at recommended doses will lead to high plasma concentrations sufficient to cause systemic toxicity. However, when the drug is used concomitantly with other local anesthetics, systemic toxic reactions may occur, since toxic effects are additive.

Systemic toxicity is rarely associated with spinal anesthesia but may occur following accidental intravascular injection of the drug. Systemic adverse reactions are characterized by tongue numbness, dizziness, and tremor, followed by seizures and cardiovascular disturbances.

Treatment of acute systemic toxicity

In case of mild symptoms of systemic toxicity, treatment is not required. However, if seizures occur, it is essential to ensure adequate oxygenation and to terminate seizure activity if it persists for more than 15–30 seconds. Oxygen should be administered via a face mask, and ventilation should be monitored and supported as needed. Seizures may be controlled by intravenous administration of thiopental at a dose of 100–150 mg or diazepam at a dose of 5–10 mg. Additionally, intravenous succinylcholine at a dose of 50–100 mg may be administered, but only if the physician is able to perform tracheal intubation and manage a fully paralyzed patient.

Manifestations of extensive or complete spinal blockade leading to respiratory paralysis should be managed by ensuring and maintaining airway patency; oxygen should be provided to assist or control lung ventilation.

Arterial hypotension should be treated with vasopressor agents, e.g., intravenous ephedrine 10–15 mg, repeated as necessary until the desired blood pressure level is achieved. Intravenous administration of fluids, electrolytes, and colloidal solutions may also rapidly alleviate arterial hypotension.

Pediatric population

Adverse reactions to the drug in children are similar to those in adults. However, early signs of local anesthetic toxicity may be difficult to detect in children when blockade is performed under sedation or general anesthesia.

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 25 °C. Do not freeze. Keep out of reach of children.

Incompatibility.

Addition of any other medicinal products to spinal solutions is not recommended.

Packaging.

5 ml in vials, 5 vials per pack.

Prescription category. Prescription only.

Manufacturer: LLC "Yuria-Pharm".

Manufacturer's address and location of operations.