English name: levobupivacaine hydrochloride injection
Chinese pinyin: levobupivacaine hydrochloride injection The main component of this product is levobupivacaine hydrochloride.
Chemical name: (S)- 1- butyl-n-(2,6-xylyl) -2- piperidinecarboxamide hydrochloride.
Molecular formula: c18h28n2o.hcl.
Molecular weight: 324.9
Accessories: sodium chloride, sodium hydroxide, hydrochloric acid, water for injection. Levobupivacaine can only be used by trained and experienced clinicians or under their supervision.
If it is necessary to block dense motor nerves for deep anesthesia or long-term anesthesia (such as epidural or paraspinal nerve block), a higher concentration can be used. It is recommended to pump carefully before and during injection to avoid intravenous injection.
Before and during bolus administration, the patient should be inhaled repeatedly, and the drug should be injected slowly, and the injection amount should be increased at a rate of 7.5-30 mg/min. At the same time, we should pay close attention to the patient's vital signs and keep a dialogue with the patient.
If symptoms of poisoning appear, stop injecting drugs immediately.
Maximum dose
It is necessary to evaluate the patient's physique and physical condition, and determine the maximum dose of the patient in combination with the drug concentration, administration area and administration route. The onset and action time of block (local anesthesia) do exist individual differences. The experience of clinical research shows that sensory block takes effect in 10- 15 minutes after epidural administration, which is suitable for surgery, and the block subsides after about 6-9 hours.
The recommended maximum single dose is 150mg. If continuous and long-term motor and sensory block is needed, the dose should be increased. The maximum recommended dose within 24 hours is 400 mg.
Obstetric dose
For cesarean section, the concentration of drug solution should not exceed 5.0 mg/ml (see contraindications). The maximum recommended dose is 150mg.
Child dose
The safety and efficacy of levobupivacaine in children are not clear.
Special crowd management
For patients with infirmity, old age or acute attack, the dose of levobupivacaine should be appropriately reduced according to their physical condition.
There is no relevant dose data for patients with impaired liver function (see Precautions and Pharmacokinetics). Adverse reactions of amide local anesthetics are very rare. However, when the drug dose is too high or intravenous injection is unintentional, adverse reactions may occur and may be dangerous.
Accidental intrathecal injection of local anesthetic may lead to high spinal anesthesia, causing asphyxia, severe hypotension and loss of consciousness.
Central nervous system effects: tongue paralysis, mild headache, dizziness, blurred vision and muscle spasm, followed by drowsiness, convulsions, unconsciousness and possible respiratory arrest.
Cardiovascular effect is related to inhibiting cardiac conduction system and reducing myocardial excitability and contractility. This may lead to decreased cardiac output, hypotension and ECG changes, indicating cardiac block, bradycardia or ventricular tachycardia (which may lead to cardiac arrest). Major central nervous system toxicity (such as convulsion) usually occurs first, but in rare cases, cardiac arrest can occur without precursor central nervous system effect.
Nerve injury is rare, but it is easy to determine that it is the result of local anesthesia, especially epidural anesthesia and spinal anesthesia.
This kind of injury may be caused by direct injury of spinal cord or spinal nerve, anterior spinal artery syndrome, injection of irritant substances or injection of non-sterile solution. Results It can cause local sensory abnormality or loss, exercise fatigue, loss of sphincter control function and paraplegia. In rare cases, these injuries may be permanent.
Post-listing report
Spasm after accidental intravenous injection is very rare. Levobupivacaine solution is contraindicated in patients who are known to be allergic to levobupivacaine, amide local anesthetics or any excipient.
Levobupivacaine solution is prohibited for intravenous local anesthesia (Beer's block).
Levobupivacaine solution is prohibited for obstetric paracervical block (see medication for pregnant women and lactating women).
Levobupivacaine solution is contraindicated in patients with severe hypotension, such as cardiogenic or hypovolemic shock. When levobupivacaine is used in various types of local and regional anesthesia, it should be equipped with good facilities. Anesthesiologists should be trained, master the necessary anesthesia techniques and be able to diagnose and deal with any possible adverse reactions.
Patients with impaired cardiovascular function, such as severe arrhythmia, should use levobupivacaine with caution.
Local central nervous system anesthesia for patients with existing central nervous system diseases, intrathecal or epidural anesthesia may aggravate the condition. Therefore, if you intend to perform epidural or intrathecal anesthesia on such patients, you should judge the clinical situation.
Sacral canal anesthesia
When levobupivacaine injection is used for epidural anesthesia, it should be given in different doses (the dose should be increased by 3-5 ml), and there should be enough interval between the two doses to find the poisoning manifestations of unintentional intravascular or intrathecal injection.
When injecting large doses (such as epidural block), it is recommended to use 3-5ml lidocaine containing adrenaline for testing. Inadvertent intravascular injection shows a temporary increase in heart rate, and unintentional intrathecal injection will show signs of spinal cord stagnation.
When injecting continuously (or intermittently) through the catheter, the syringe should also be aspirated before or during each additional injection. Even if blood is not seen during aspiration, intravenous injection may still occur. During epidural anesthesia, it is recommended to use the trial dose initially and monitor the effect of the drug before giving the full dose. Epidural anesthesia with any local anesthetic may lead to hypotension and bradycardia. All patients must establish venous access. Appropriate fluids, pressors, anticonvulsants, muscle relaxants, atropine and resuscitation equipment must be available, and professional resuscitation skills must be mastered (see drug overdose).
Used for special people
Weak, elderly or acute attack patients: patients with weak, elderly or acute attack should use levobupivacaine with caution (see usage and dosage).
Liver injury: Because levobupivacaine is metabolized in the liver, patients with liver disease or patients with decreased liver blood flow (such as alcoholics or cirrhosis patients) should use levobupivacaine with caution (see pharmacokinetics).
Influence on the ability to drive and operate machines
Levobupivacaine seriously affects the ability of drug addicts to drive or operate machines. Therefore, patients should not drive or operate machines until all anesthetic effects and direct surgical effects have subsided. other
Disposable use. The drug solution should be used immediately after the package is opened. The remaining liquid medicine should be discarded.
The diluent of levobupivacaine should be prepared with 0.9% sodium chloride solution under aseptic operation for injection. The diluted liquid medicine can be used at 20-22℃ for 7 days, and the mixed solution of clonidine, morphine and fentanyl can still be used at 20-22℃ for 40 hours. To avoid microbial contamination, it is recommended to use it immediately. Otherwise, the user is responsible for storing the time and conditions.
If levobupivacaine is diluted with alkaline solution, precipitation will occur. Levobupivacaine can not be diluted with sodium bicarbonate solution, nor can it be used at the same time. Except the above drugs (it has been proved that clonidine 8.4ug/ml, morphine 0.05mg/ml and fentanyl 4ug/ml are compatible with levobupivacaine diluted with 0.9% sodium chloride solution), this product cannot be mixed with other drugs.
If the medicine has passed the expiration date marked on the medicine bottle, it can no longer be used.
Please keep the medicine out of the reach of children. be pregnant
Levobupivacaine solution is forbidden to be used in obstetric paracervical block. According to the experience of using bupivacaine, fetal bradycardia may occur after paracervical block (see contraindications).
At present, there is no clinical data of levobupivacaine used in the first trimester of pregnancy. Animal studies have not shown that levobupivacaine has teratogenic effect, but embryo-fetal toxicity has been observed at the same systemic exposure dose as clinic (see pharmacology and toxicology). The potential danger of levobupivacaine to people is not clear. Therefore, levobupivacaine should not be used for early pregnancy unless it is really necessary.
However, up to now, the clinical experience of using bupivacaine in obstetric surgery (pregnancy or delivery) has been rich, but it has not been proved that bupivacaine has fetal toxicity.
Nursing with breast milk
It is not clear whether levobupivacaine is excreted through milk. However, like bupivacaine, levobupivacaine may be difficult to secrete through milk. Therefore, breast-feeding can be carried out after local anesthesia. In vitro studies show that CYP3A4 isoenzymes and CYP 1A2 isoenzymes mediate the metabolism of levobupivacaine. Although clinical studies have not been conducted, the metabolism of levobupivacaine may be affected by CYP3A4 inhibitors (such as ketoconazole) and CYP 1A2 inhibitors (methylxanthine).
Patients receiving antiarrhythmic drugs with local anesthetic activity (mexiletine) or class III antiarrhythmic drugs should use levobupivacaine with caution, because the toxic reactions of these drugs may accumulate.
At present, there is no clinical study to evaluate the combined use of levobupivacaine and epinephrine. During local anesthesia, unintentional intravenous injection of anesthetic can lead to acute toxic reactions. When the dose is too large, the peak blood concentration can only be reached after 2 hours of injection (depending on the injection site), so the toxic signs may be delayed. The time for the drug to take effect may be prolonged.
It is reported that excessive use of long-acting local anesthetics or unintentional intravenous injection can produce systemic adverse reactions, including central nervous system and cardiovascular reactions.
Central nervous system response
When convulsion occurs, thiopental sodium should be injected intravenously immediately, and diazepam should be injected intravenously if necessary. Thiopental sodium and diazepam can also inhibit the central nervous system, respiratory and cardiac functions. Therefore, the use of thiopental sodium and diazepam may lead to suffocation. Neuromuscular blockers can only be used when clinicians are convinced that they can keep the patient's airway unobstructed and can treat the patient under general anesthesia.
If not treated in time, convulsions caused by the effect of local anesthetics on the heart and subsequent hypoxia, hypercapnia and myocardial inhibition may lead to arrhythmia, ventricular fibrillation or cardiac arrest.
Cardiovascular effect
Before treatment, rehydration and/or antihypertensive drugs can prevent or relieve hypotension. If hypotension occurs, crystal or colloidal solution should be injected intravenously, and/or the dose of antihypertensive drugs (such as ephedrine 5- 10 mg) should be increased. At the same time, all co-existing causes of hypotension should be dealt with immediately.
If severe bradycardia occurs, atropine should be given 0.3- 1.0 mg. This therapy usually restores the patient's heart rate to an acceptable level. Arrhythmia should be treated as needed, and ventricular fibrillation should be cardioverted. pharmacological action
Levobupivacaine is an amide local anesthetic, which can increase the threshold of nerve action potential, delay the expansion of nerve impulse, and slow down the rising speed of action potential, thus blocking the generation and conduction of nerve impulse. The anesthetic effect is related to the axial diameter of nerve fibers, myelination and conduction velocity.
Toxicological study
Genotoxicity: the mutagenicity of levobupivacaine was not found in bacterial mutation test, mouse lymphoma mutation test, human lymphocyte chromosome aberration test and mouse bone marrow micronucleus test.
Reproductive toxicity: rats were given levobupivacaine 18mg/kg/d (converted by body surface area, the dose was about half of the maximum clinical dose), but the fertility of parents and offspring animals was not affected. When levobupivacaine is given to lactating rats, a small amount of drugs can be detected in young rats. In human studies, the distribution kinetics of levobupivacaine after intravenous administration is basically the same as that of bupivacaine. After therapeutic administration, the plasma concentration of levobupivacaine depends on the dosage and route of administration, because the absorption of drugs from the injection site is affected by the vascular distribution of tissues.
For patients with liver injury, there is no relevant information (see precautions).
For patients with renal damage, there is no data at present. Levobupivacaine can be completely metabolized, and there is no prototype levobupivacaine in urine.
Some studies have evaluated the plasma protein binding rate of levobupivacaine in male patients in vitro. The results showed that the plasma protein binding rate was more than 97% when the concentration of levobupivacaine was 0. 1- 1.0μ g/ml.
In clinical pharmacology research, the average half-life of intravenous levobupivacaine (40mg) is about (80 22) minutes, the Cmax (maximum plasma concentration) is (1.4 0.2) μ g/ml, and the AUC (area under the curve) is (70 27) μ g/min.
When levobupivacaine 75mg(0.5%) and 1 12.5mg(0.75%) and 1mg/kg(0.25%) and 2mg/kg(0.5%) were used for brachial plexus block, the average maximum of levobupivacaine was obtained. 1 12.5mg(0.75%) levobupivacaine used for epidural anesthesia, the average maximum plasma concentration and AUC value were 0.58 μg /ml and 3.56 μ g h/ml, respectively.
After intravenous infusion, the average total plasma clearance and terminal half-life of levobupivacaine were 39 liters/hour and 65438 0.3 hours, respectively. After intravenous administration, the distribution volume of levobupivacaine was 67 liters.
Levobupivacaine can be completely metabolized, so the prototype levobupivacaine will not be detected in urine or feces. The main metabolite of levobupivacaine, 3- hydroxy levobupivacaine, is secreted in urine in the form of glucuronic acid and sulfate. In vitro studies have proved that CYP3A4 isomer and CYP 1A2 isomer mediate the metabolism of levobupivacaine, which is transformed into debutyl bupivacaine and 3- hydroxy levobupivacaine respectively. These studies show that levobupivacaine and bupivacaine have similar metabolism.
After intravenous administration, the average total recovery rate of levobupivacaine within 48 hours was about 95%, including 765,438 0% in urine and 24% in feces.
There is no evidence that levobupivacaine racemizes in vivo and in vitro. New york medicine company
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