Dyural 80-LM
(Methylprednisolone Acetate, Lidocaine Hydrochloride, Bupivacaine Hydrochloride, Povidine Iodine, Isopropyl Alcohol)Dyural 80-LM Prescribing Information
WARNING: RISK OF CARDIAC ARREST WITH USE OF BUPIVACAINE HYDROCHLORIDE INJECTION IN OBSTETRICAL ANESTHESIA
See full prescribing information for complete boxed warning.
There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration of Bupivacaine Hydrochloride Injection is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary ( 5.1).
For first aid to decrease germs in
- minor cuts
- scrapes
- burns
For preparation of the skin prior to injection
- apply to skin as needed
- discard after single use
Bupivacaine Hydrochloride Injection, USP is a clear, colorless solution available as:
- 0.25% (25 mg/10 mL) (2.5 mg/mL) in single-dose teartop vials.
- 0.25% (75 mg/30 mL) (2.5 mg/mL) in single-dose teartop vials.
- 0.25% (125 mg/50 mL) (2.5 mg/mL) in multiple-dose fliptop vials.
- 0.5% (50 mg/10 mL) (5 mg/mL) in single-dose teartop vials.
- 0.5% (150 mg/30 mL) (5 mg/mL) in single-dose teartop vials.
- 0.5% (250 mg/50 mL) (5 mg/mL) in multiple-dose fliptop vials.
- 0.75% (75 mg/10 mL) (7.5 mg/mL) in single-dose teartop vials.
- 0.75% (225 mg/30 mL) (7.5 mg/mL) in single-dose teartop vials.
Pregnancy
Risk Summary
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is contraindicated for obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death [see Contraindications (4), Warnings and Precautions (5.1)].
There are no available data on use of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection in pregnant women to inform a drug-associated risk of adverse developmental outcomes.
In animal studies, embryo-fetal lethality was noted when bupivacaine was administered subcutaneously to pregnant rabbits during organogenesis at clinically relevant doses. Decreased pup survival was observed in a rat pre- and post-natal developmental study (dosing from implantation through weaning) at a dose level comparable to the daily maximum recommended human dose (MRHD) on a body surface area (BSA) basis. Based on animal data, advise pregnant women of the potential risks to a fetus (see Data).
Local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity [see Clinical Pharmacology (12.3)]. The incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the CNS, peripheral vascular tone, and cardiac function.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Clinical Considerations
Maternal Adverse Reactions
Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. The supine position is dangerous in pregnant women at term because of aortocaval compression by the gravid uterus. Therefore, during treatment of systemic toxicity, maternal hypotension or fetal bradycardia following regional block, the parturient should be maintained in the left lateral decubitus position if possible, or manual displacement of the uterus off the great vessels be accomplished. Elevating the patient's legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable.
Labor or Delivery
Epidural, caudal, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia has been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance.
The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. This has not been reported with bupivacaine.
It is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to parturients. To do this, the patient must be maintained in the left lateral decubitus position or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left.
Data
Animal Data
Bupivacaine hydrochloride produced developmental toxicity when administered subcutaneously to pregnant rats and rabbits at clinically relevant doses.
Bupivacaine hydrochloride was administered subcutaneously to rats at doses of 4.4, 13.3, & 40 mg/kg and to rabbits at doses of 1.3, 5.8, & 22.2 mg/kg during the period of organogenesis (implantation to closure of the hard palate). The high doses are comparable to the daily MRHD of 400 mg/day on a mg/m 2 BSA basis. No embryo-fetal effects were observed in rats at the high dose which caused increased maternal lethality. An increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity with the fetal No Observed Adverse Effect Level representing approximately 0.3 times the MRHD on a BSA basis.
In a rat pre-and post-natal developmental study (dosing from implantation through weaning) conducted at subcutaneous doses of 4.4, 13.3, & 40 mg/kg, decreased pup survival was observed at the high dose. The high dose is comparable to the daily MRHD of 400 mg/day on a BSA basis.
Lactation
Risk Summary
Lactation studies have not been conducted with bupivacaine. Bupivacaine has been reported to be excreted in human milk suggesting that the nursing infant could be theoretically exposed to a dose of the drug. Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection should be administered to lactating women only if clearly indicated. Studies assessing the effects of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection in breastfed children have not been performed. Studies to assess the effect of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection on milk production or excretion have not been performed. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bupivacaine and any potential adverse effects on the breastfed child from bupivacaine or from the underlying maternal condition.
Pediatric Use
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is approved for use in adults. Administration of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection in pediatric patients younger than 12 years is not recommended.
Continuous infusions of bupivacaine in pediatric patients have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities.
Geriatric Use
Patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
In clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients.
Differences in various pharmacokinetic parameters have been observed between elderly and younger adult patients [see Clinical Pharmacology (12.3)].
This product is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Elderly patients may require lower doses of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection.
Hepatic Impairment
Amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. Patients with severe hepatic impairment, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Therefore, consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment treated with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, especially with repeat doses [see Warnings and Precautions (5.10)] .
Renal Impairment
Bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. This should be considered when selecting the Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection dosage [see Use in Specific Populations (8.5)] .
Lidocaine hydrochloride is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.
Risk of Cardiac Arrest with Use of Bupivacaine Hydrochloride Injection in Obstetrical Anesthesia
There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration of Bupivacaine Hydrochloride Injection is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.
Dose-Related Toxicity
The safety and effectiveness of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be performed after injection of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solutions.
Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death.
During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access. Use the lowest dosage of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection that results in effective anesthesia to avoid high plasma levels and serious adverse effects. Avoid rapid injection of a large volume of Bupivacaine. Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solution and administer fractional (incremental) doses when feasible.
Injection of repeated doses of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection may cause significant increases in plasma levels with each repeated dose due to slow accumulation of the drug or its metabolites, or to slow metabolic degradation. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical status.
Methemoglobinemia
Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition [see Drug Interactions (7.5)] . If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.
Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious CNS and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Antimicrobial Preservatives in Multiple-Dose Vials
Avoid use of Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection solutions containing antimicrobial preservatives, i.e., those supplied in multiple-dose vials, for epidural or caudal anesthesia because safety has not been established with such use.
Chondrolysis with Intra-Articular Infusion
Intra-articular infusions of local anesthetics including Bupivacaine Hydrochloride Injection following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are associated with chondrolysis. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2 nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.
Risk of Adverse Reactions Due to Drug Interactions with Bupivacaine Hydrochloride and Epinephrine Injection
Risk of Severe, Persistent Hypertension Due to Drug Interactions Between Bupivacaine Hydrochloride and Epinephrine Injection and Monoamine Oxidase Inhibitors and Tricyclic Antidepressants
Administration of Bupivacaine Hydrochloride and Epinephrine Injection (containing a vasoconstrictor) in patients receiving monoamine oxidase inhibitors (MAOI), or tricyclic antidepressants may result in severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient's hemodynamic status is essential [see Drug Interactions (7.2)].
Risk of Severe, Persistent Hypertension or Cerebrovascular Accidents Due to Drug Interactions Between Bupivacaine Hydrochloride and Epinephrine Injection and Ergot-Type Oxytocic Drugs
Concurrent administration of Bupivacaine Hydrochloride and Epinephrine Injection and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Avoid use of Bupivacaine Hydrochloride and Epinephrine Injection concomitantly with ergot-type oxytocic drugs [see Drug Interactions (7.3)] .
Risk of Hypertension and Bradycardia Due to Drug Interactions Between Bupivacaine Hydrochloride and Epinephrine Injection and Nonselective Beta-Adrenergic Antagonists
Administration of Bupivacaine Hydrochloride and Epinephrine Injection (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient's blood pressure and heart rate is essential [see Drug Interactions (7.4)] .
Risk of Cardiac Arrest with Intravenous Regional Anesthesia Use (Bier Block)
There have been reports of cardiac arrest and death during the use of bupivacaine for intravenous regional anesthesia (Bier Block). Information on safe dosages and techniques of administration of Bupivacaine Hydrochloride Injection in this procedure is lacking. Therefore, Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection is contraindicated for use with this technique [see Contraindications (4)] .
Allergic-Type Reactions to Sulfites in Bupivacaine Hydrochloride and Epinephrine Injection
Bupivacaine Hydrochloride and Epinephrine Injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Bupivacaine Hydrochloride Injection without epinephrine does not contain sodium metabisulfite.
Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection
Unintended intravascular or intrathecal injection of. Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest. Unintentional intrathecal injection during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column has resulted in underventilation or apnea ("Total or High Spinal"). A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia [see Adverse Reactions (6)] .
Aspirate for blood or cerebrospinal fluid (where applicable) before injecting Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, both the initial dose and all subsequent doses, to avoid intravascular or intrathecal injection. However, a negative aspiration for blood or cerebrospinal fluid does not ensure against an intravascular or intrathecal injection.
Use of Test Dose with Epidural Anesthesia
To serve as a warning of unintended intravascular or intrathecal injection, 3 mL of Bupivacaine Hydrochloride and Epinephrine Injection without antimicrobial preservative (0.5% bupivacaine with 1:200,000 epinephrine) may be used as a test dose prior to administration of the full dose in caudal and lumbar epidural blocks [see Dosage and Administration (2.4)] . Three mL of Bupivacaine Hydrochloride and Epinephrine Injection without antimicrobial preservative (0.5% bupivacaine with 1:200,000 epinephrine) contains 15 mg bupivacaine and 15 mcg epinephrine. An intravascular or intrathecal injection is still possible even if results of the test dose are negative.
Signs/symptoms of unintended intravascular or intrathecal injection of the test dose of Bupivacaine Hydrochloride and Epinephrine Injection and monitoring recommendations are described below.
- Unintended intravascular injection: Likely to produce a transient "epinephrine response" within 45 seconds, consisting of an increase in heart rate and/or systolic blood pressure, circumoral pallor, palpitations, and nervousness in the unsedated patient. The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds. Therefore, following the test dose, the heart rate should be monitored for increases. Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect a transient rise in systolic blood pressure.
- Unintended intrathecal injection: Evidenced within a few minutes by signs of spinal block (e.g., decreased sensation of the buttocks, paresis of the legs, or, in the sedated patient, absent knee jerk).
The test dose itself may produce a systemic toxic reaction, high spinal or epinephrine-induced cardiovascular effects [see Overdosage (10)] .
Risk of Toxicity in Patients with Hepatic Impairment
Because amide local anesthetics such as bupivacaine are metabolized by the liver, consider reduced dosing and increased monitoring for bupivacaine systemic toxicity in patients with moderate to severe hepatic impairment who are treated Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection, especially with repeat doses [see Use in Specific Populations (8.6)].
Risk of Use in Patients with Impaired Cardiovascular Function
Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection should be given in reduced doses in patients with impaired cardiovascular function (e.g., hypotension, heartblock) because they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection. Monitor patients closely for blood pressure, heart rate, and ECG changes.
Risk of Ischemic Injury or Necrosis in Body Areas with Limited Blood Supply
Use Bupivacaine Hydrochloride and Epinephrine Injection in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply such as digits, nose, external ear, or penis. Patients with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result.
Risk of Cardiac Arrhythmias with Concomitant Use of Potent Inhalation Anesthetics
Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Drug Interactions (7.6)] . In deciding whether to concurrently use Bupivacaine Hydrochloride and Epinephrine Injection with potent inhalation anesthetics in the same patient, the combined action of both agents upon the myocardium, the concentration and volume of vasoconstrictor used, and the time since injection, when applicable, should be taken into account.
Risk of Adverse Reactions with Use in Head and Neck Area
Small doses of local anesthetics (e.g., Bupivacaine Hydrochloride Injection) injected into the head and neck area, including retrobulbar, dental, and stellate ganglion blocks, may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. The injection procedures require the utmost care. Confusion, convulsions, respiratory depression, and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation. They may also be due to puncture of the dural sheath of the optic nerve during retrobulbar block with diffusion of any local anesthetic along the subdural space to the midbrain. Monitor circulation and respiration and constantly observe patients receiving Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection blocks. Resuscitative equipment and drugs, and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded [see Dosage and Administration (2.2)].
Risk of Respiratory Arrest with Use in Ophthalmic Surgery
Clinicians who perform retrobulbar blocks should be aware that there have been reports of respiratory arrest following local anesthetic injection. Prior to retrobulbar block (e.g., with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection), as with all other regional procedures, resuscitative equipment and drugs, and personnel to manage respiratory arrest or depression, convulsions, and cardiac stimulation or depression should be immediately available [see Warnings and Precautions (5.14)]. As with other anesthetic procedures, patients should be constantly monitored following ophthalmic blocks for signs of these adverse reactions, which may occur following relatively low total doses.
A concentration of 0.75% bupivacaine is indicated for retrobulbar block; however, this concentration is not indicated for any other peripheral nerve block, including the facial nerve, and not indicated for local infiltration, including the conjunctiva [see Indications and Usage (1)].
Risk of Inadvertent Trauma to Tongue, Lips, and Buccal Mucosa in Dental Applications
Because of the long duration of anesthesia, when Bupivacaine Hydrochloride and Epinephrine Injection [0.5% (5 mg/mL) of bupivacaine] is used for dental injections, warn patients about the possibility of inadvertent trauma to tongue, lips, and buccal mucosa and advise them not to chew solid foods until sensation returns [see Patient Counseling Information (17)] .
Systemic
Adverse experiences following the administration of lidocaine hydrochloride are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption or inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported:
Central Nervous System
CNS manifestations are excitatory and/or depressant and may be characterized by lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest.
Drowsiness following the administration of lidocaine hydrochloride is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption.
Cardiovascular System
Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.
Allergic
Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Allergic reactions may occur as a result of sensitivity to local anesthetic agents. Allergic reactions, including anaphylactic reactions, may occur as a result of sensitivity to lidocaine, but are infrequent. If allergic reactions do occur, they should be managed by conventional means. The detection of sensitivity by skin testing is of doubtful value.
There have been no reports of cross sensitivity between lidocaine hydrochloride and procainamide or between lidocaine hydrochloride and quinidine.
Neurologic
The incidences of adverse reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration and the physical status of the patient. In a prospective review of 10,440 patients who received lidocaine hydrochloride for spinal anesthesia, the incidences of adverse reactions were reported to be about 3 percent each for positional headaches, hypotension and backache; 2 percent for shivering; and less than 1 percent each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic.
In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter may occur. Subsequent adverse effects may depend partially on the amount of drug administered subdurally. These may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances when caudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anesthetic procedures.
There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration.
Hematologic
Methemoglobinemia.
Clinically Significant Drug Interactions
The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension.
Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.
Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.
Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
Lidocaine hydrochloride injection, USP is sterile, nonpyrogenic, aqueous solution that contains a local anesthetic agent and is administered parenterally by injection. See INDICATIONS AND USAGE section for specific uses.
Lidocaine hydrochloride injection, USP contains lidocaine hydrochloride, which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular weight 270.8. Lidocaine hydrochloride (C 14H 22N 2O • HCl) has the following structural formula:
Lidocaine hydrochloride injection, USP is a sterile, nonpyrogenic, isotonic solution containing sodium chloride. The pH of the solution is adjusted to approximately 6.5 (5.0 to 7.0) with sodium hydroxide and/or hydrochloric acid.
Mechanism of Action
Lidocaine hydrochloride stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.
Hemodynamics
Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded.
Pharmacokinetics and Metabolism
Information derived from diverse formulations, concentrations and usages reveals that lidocaine hydrochloride is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.
The plasma binding of lidocaine hydrochloride is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL 60 to 80 percent of lidocaine hydrochloride is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
Lidocaine hydrochloride crosses the blood-brain and placental barriers, presumably by passive diffusion.
Lidocaine hydrochloride is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine hydrochloride. Approximately 90% of lidocaine hydrochloride administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.
The elimination half-life of lidocaine hydrochloride following an intravenous bolus injection is typically 1.5 to 2 hours. Because of the rapid rate at which lidocaine hydrochloride is metabolized, any condition that affects liver function may alter lidocaine hydrochloride kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine hydrochloride kinetics but may increase the accumulation of metabolites.
Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine hydrochloride required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg free base per mL. In the rhesus monkey arterial blood levels of 18 to 21 mcg/mL have been shown to be threshold for convulsive activity.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term studies in animals to evaluate the carcinogenic potential of bupivacaine hydrochloride have not been conducted.
Mutagenesis
The mutagenic potential of bupivacaine hydrochloride has not been determined.
Impairment of Fertility
The effect of bupivacaine on fertility has not been determined.
Lidocaine Hydrochloride Injection, USP is supplied as follows:
Lidocaine Hydrochloride Injection USP, 1% (10 mg/mL)
5 mL Single Dose Vials in a Carton of 10 NDC 55150-162-05
Sterile, Nonpyrogenic
Discard unused portion
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
The vial stopper is not made with natural rubber latex.
Distributed by:
AuroMedics Pharma LLC
279 Princeton-Hightstown Rd.
E. Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad - 500038
India
Revised: February 2020
Mechanism of Action
Bupivacaine blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.
Epinephrine is a vasoconstrictor added to bupivacaine to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.
For external use only
Flammable - keep away from fire or flame
Do not use
with electrocautery procedures
When using this product do not
- get into eyes
- apply over large areas of the body
- in case of deep or puncture wounds, animal bites or serious burns consult a doctor
Stop use and ask a doctor if
- condition persists or gets worse or lasts for more than 72 hours
- do not use longer than 1 week unless directed by a doctor
Keep out of reach of children.
If swallowed, get medical help or contact a Poison Control Center right away.