Label: MARLIDO KIT- marcaine, lidocaine, povidone iodine kit

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: unapproved drug other

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Drug Label Information

Updated November 1, 2018

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  • SPL UNCLASSIFIED SECTION


    Rx only

  • DESCRIPTION

    Bupivacaine hydrochloride USP is 2-Piperidinecarboxamide, 1-butyl- N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate, a white, odorless, crystalline powder that is freely soluble in 95 percent ethanol, soluble in water, and slightly soluble in chloroform or acetone. It has the following structural formula:

    Chemical Structure

    Bupivacaine hydrochloride injection, USP is available in sterile isotonic solution for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Solution of bupivacaine hydrochloride injection, USP may be autoclaved. Solution is clear and colorless.



    Bupivacaine is related chemically and pharmacologically to the aminoacyl local anesthetics. It is a homologue of mepivacaine and is chemically related to lidocaine. All three of these anesthetics contain an amide linkage between the aromatic nucleus and the amino, or piperidine group. They differ in this respect from the procaine-type local anesthetics, which have an ester linkage.



    Bupivacaine hydrochloride injection, USP — Sterile isotonic solution containing sodium chloride. The pH of the solution is adjusted to between 4 and 6.5 with sodium hydroxide or hydrochloric acid.

  • CLINICAL PHARMACOLOGY


    Local anesthetics block 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.

    Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems (CNS). At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias, and cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Recent clinical reports and animal research suggest that these cardiovascular changes are more likely to occur after unintended intravascular injection of bupivacaine. Therefore, incremental dosing is necessary.

    Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression, or both. Apparent central stimulation is manifested as restlessness, tremors and shivering progressing to convulsions, followed by depression and coma progressing ultimately to respiratory arrest. However, the local anesthetics have a primary depressant effect on the medulla and on higher centers. The depressed stage may occur without a prior excited state.

    Pharmacokinetics


    The rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution. A dilute concentration of epinephrine (1:200,000 or 5 mcg/mL) usually reduces the rate of absorption and peak plasma concentration of bupivacaine, permitting the use of moderately larger total doses and sometimes prolonging the duration of action.

    The onset of action with bupivacaine is rapid and anesthesia is long lasting. The duration of anesthesia is significantly longer with bupivacaine than with any other commonly used local anesthetic. It has also been noted that there is a period of analgesia that persists after the return of sensation, during which time the need for strong analgesics is reduced.

    Local anesthetics are bound to plasma proteins in varying degrees. Generally, the lower the plasma concentration of drug the higher the percentage of drug bound to plasma proteins.

    Local anesthetics appear to cross the placenta by passive diffusion. The rate and degree of diffusion is governed by (1) the degree of plasma protein binding, (2) the degree of ionization, and (3) the degree of lipid solubility. Fetal/maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding, because only the free, unbound drug is available for placental transfer. Bupivacaine with a high protein binding capacity (95%) has a low fetal/maternal ratio (0.2 to 0.4). The extent of placental transfer is also determined by the degree of ionization and lipid solubility of the drug. Lipid soluble, nonionized drugs readily enter the fetal blood from the maternal circulation.

    Depending upon the route of administration, local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs such as the liver, lungs, heart, and brain.

    Pharmacokinetic studies on the plasma profile of bupivacaine after direct intravenous injection suggest a three-compartment open model. The first compartment is represented by the rapid intravascular distribution of the drug. The second compartment represents the equilibration of the drug throughout the highly perfused organs such as the brain, myocardium, lungs, kidneys, and liver. The third compartment represents an equilibration of the drug with poorly perfused tissues, such as muscle and fat. The elimination of drug from tissue distribution depends largely upon the ability of binding sites in the circulation to carry it to the liver where it is metabolized.

    After injection of bupivacaine hydrochloride for caudal, epidural, or peripheral nerve block in man, peak levels of bupivacaine in the blood are reached in 30 to 45 minutes, followed by a decline to insignificant levels during the next three to six hours.

    Various pharmacokinetic parameters of the local anesthetics can be significantly altered by the presence of hepatic or renal disease, addition of epinephrine, factors affecting urinary pH, renal blood flow, the route of drug administration, and the age of the patient. The half-life of bupivacaine in adults is 2.7 hours and in neonates 8.1 hours.

    In clinical studies, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger patients. Elderly patients also exhibited higher peak plasma concentrations following administration of this product. The total plasma clearance was decreased in these patients.

    Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid. Patients with hepatic disease, especially those with severe hepatic disease, may be more susceptible to the potential toxicities of the amide-type local anesthetics. Pipecoloxylidine is the major metabolite of bupivacaine.

    The kidney is the main excretory organ for most local anesthetics and their metabolites. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH. Only 6% of bupivacaine is excreted unchanged in the urine.

    When administered in recommended doses and concentrations, bupivacaine hydrochloride does not ordinarily produce irritation or tissue damage and does not cause methemoglobinemia.

  • INDICATIONS AND USAGE


    Bupivacaine hydrochloride injection, USP is indicated for the production of local or regional anesthesia or analgesia for surgery, oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. Only the 0.25% and 0.5% concentrations are indicated for obstetrical anesthesia. (See WARNINGS.)

    Experience with nonobstetrical surgical procedures in pregnant patients is not sufficient to recommend use of 0.75% concentration of bupivacaine hydrochloride injection, USP in these patients.

    Bupivacaine hydrochloride injection, USP is not recommended for intravenous regional anesthesia (Bier Block). See WARNINGS.

    The routes of administration and indicated bupivacaine hydrochloride injection, USP concentrations are:


    • local infiltration                          0.25%
    • peripheral nerve block               0.25% and 0.5%
    • retrobulbar block                       0.75%
    • sympathetic block                     0.25%
    • lumbar epidural                         0.25%, 0.5%, and 0.75% (0.75% not for obstetrical anesthesia)
    • caudal                                        0.25% and 0.5%
    • epidural test dose                      (see PRECAUTIONS)

    (See DOSAGE AND ADMINISTRATION for additional information.)

    Standard textbooks should be consulted to determine the accepted procedures and techniques for the administration of bupivacaine hydrochloride injection, USP.

  • CONTRAINDICATIONS


    Bupivacaine hydrochloride injection is contraindicated in obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death.

    Bupivacaine hydrochloride injection is contraindicated in patients with a known hypersensitivity to it or to any local anesthetic agent of the amide-type.

  • WARNINGS


    THE 0.75% CONCENTRATION OF BUPIVACAINE HYDROCHLORIDE IS NOT RECOMMENDED FOR OBSTETRICAL ANESTHESIA. THERE HAVE BEEN REPORTS OF CARDIAC ARREST WITH DIFFICULT RESUSCITATION OR DEATH DURING USE OF BUPIVACAINE HYDROCHLORIDE FOR EPIDURAL ANESTHESIA IN OBSTETRICAL PATIENTS. IN MOST CASES, THIS HAS FOLLOWED USE OF THE 0.75% 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% CONCENTRATION SHOULD BE RESERVED FOR SURGICAL PROCEDURES WHERE A HIGH DEGREE OF MUSCLE RELAXATION AND PROLONGED EFFECT ARE NECESSARY.

    LOCAL ANESTHETICS SHOULD ONLY BE EMPLOYED BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES WHICH MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED, AND THEN ONLY AFTER INSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY RESUSCITATIVE EQUIPMENT, AND THE PERSONNEL RESOURCES NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES. (See also ADVERSE REACTIONS, PRECAUTIONS, and OVERDOSAGE.) 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.



    Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been postmarketing 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 not associated with these findings. 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 2nd 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.



    It is essential that aspiration for blood or cerebrospinal fluid (where applicable) be done prior to injecting any local anesthetic, both the original dose and all subsequent doses, to avoid intravascular or subarachnoid injection. However, a negative aspiration does not ensure against an intravascular or subarachnoid injection.



    Until further experience is gained in pediatric patients younger than 12 years, administration of bupivacaine hydrochloride in this age group is not recommended.



    Mixing or the prior or intercurrent use of any other local anesthetic with bupivacaine hydrochloride cannot be recommended because of insufficient data on the clinical use of such mixtures.



    There have been reports of cardiac arrest and death during the use of bupivacaine hydrochloride for intravenous regional anesthesia (Bier Block). Information on safe dosages and techniques of administration of bupivacaine hydrochloride in this procedure is lacking. Therefore, bupivacaine hydrochloride is not recommended for use in this technique.

    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. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.

    Signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue bupivacaine and any other oxidizing agents. Depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

  • PRECAUTIONS

    General


    The safety and effectiveness of local anesthetics depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use. (See WARNINGS, ADVERSE REACTIONS, and OVERDOSAGE. ) During major regional nerve blocks, the patient should have IV fluids running via an indwelling catheter to assure a functioning intravenous pathway. The lowest dosage of local anesthetic that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. The rapid injection of a large volume of local anesthetic solution should be avoided and fractional (incremental) doses should be used when feasible.

    Epidural Anesthesia


    During epidural administration of bupivacaine hydrochloride, 0.5% and 0.75% solutions should be administered in incremental doses of 3 mL to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. Injections should be made slowly, with frequent aspirations before and during the injection to avoid intravascular injection. Syringe aspirations should also be performed before and during each supplemental injection in continuous (intermittent) catheter techniques. An intravascular injection is still possible even if aspirations for blood are negative.

    During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and the effects monitored before the full dose is given. When using a “continuous” catheter technique, test doses should be given prior to both the original and all reinforcing doses, because plastic tubing in the epidural space can migrate into a blood vessel or through the dura. When clinical conditions permit, the test dose should contain epinephrine (10 mcg to 15 mcg has been suggested) to serve as a warning of unintended intravascular injection. If injected into a blood vessel, this amount of epinephrine is 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 a heart rate increase. Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect a transient rise in systolic blood pressure. The test dose should also contain 10 mg to 15 mg of bupivacaine hydrochloride or an equivalent amount of another local anesthetic to detect an unintended intrathecal administration. This will be 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 formulation of bupivacaine hydrochloride contains 15 mg of bupivacaine and 15 mcg of epinephrine in a volume of 3 mL. An intravascular or subarachnoid injection is still possible even if results of the test dose are negative. The test dose itself may produce a systemic toxic reaction, high spinal or epinephrine-induced cardiovascular effects.

    Injection of repeated doses of local anesthetics 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. Local anesthetics should also be used with caution in patients with hypotension or heartblock.

    Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be performed after each local anesthetic injection. It should be kept in mind at such times that restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, depression, or drowsiness may be early warning signs of central nervous system toxicity.

    Local anesthetic solutions containing a vasoconstrictor should be used cautiously and 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.

    Because amide-local anesthetics such as bupivacaine are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. Local anesthetics should also be used with caution in patients with impaired cardiovascular function because they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by these drugs.

    Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine are employed in patients during or following the administration of potent inhalation anesthetics. In deciding whether to use these products concurrently 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.

    Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Because it is not known whether amide-type local anesthetics may trigger this reaction and because the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for management should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and prompt institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene. (Consult dantrolene sodium intravenous package insert before using.)

    Use in Head and Neck Area


    Small doses of local anesthetics injected into the head and neck area, including retrobulbar, 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. Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed. Resuscitative equipment and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded. (See DOSAGE AND ADMINISTRATION. )

    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, as with all other regional procedures, the immediate availability of equipment, drugs, and personnel to manage respiratory arrest or depression, convulsions, and cardiac stimulation or depression should be assured (see also WARNINGS and Use in Head and Neck Area, above). 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 and PRECAUTIONS, General). Mixing bupivacaine hydrochloride with other local anesthetics is not recommended because of insufficient data on the clinical use of such mixtures.

    When bupivacaine hydrochloride 0.75% is used for retrobulbar block, complete corneal anesthesia usually precedes onset of clinically acceptable external ocular muscle akinesia. Therefore, presence of akinesia rather than anesthesia alone should determine readiness of the patient for surgery.

    Information for Patients

    When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of caudal or epidural anesthesia. Also, when appropriate, the physician should discuss other information including adverse reactions in the package insert of bupivacaine hydrochloride.

    Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to stop use and seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

    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. 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 and of ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.

    Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.

    Patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents:

    Class

    Examples

    Nitrates/Nitrites

    nitroglycerin, nitroprusside, nitric oxide, nitrous oxide

    Local anesthetics

    benzocaine, lidocaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, articaine, ropivacaine

    Antineoplastic agents

    cyclophosphamide, flutamide, rasburicase, ifosfamide, hydroxyurea

    Antibiotics

    dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid

    Antimalarials

    chloroquine, primaquine

    Anticonvulsants

    phenytoin, sodium valproate, phenobarbital

    Other drugs

    acetaminophen, metoclopramide, sulfa drugs (i.e., sulfasalazine), quinine

    Carcinogenesis, Mutagenesis, Impairment of Fertility


    Long-term studies in animals to evaluate the carcinogenic potential of bupivacaine hydrochloride have not been conducted. The mutagenic potential and the effect on fertility of bupivacaine hydrochloride have not been determined.

    Pregnancy Category C


    There are no adequate and well-controlled studies in pregnant women. Bupivacaine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Bupivacaine hydrochloride produced developmental toxicity when administered subcutaneously to pregnant rats and rabbits at clinically relevant doses. This does not exclude the use of bupivacaine hydrochloride at term for obstetrical anesthesia or analgesia. (See Labor and Delivery)

    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 maximum recommended human dose (MRHD) of 400 mg/day on a mg/m 2 body surface area (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 1/5th the MRHD on a BSA basis.

    In a rat pre- and post-natal development study (dosing from implantation through weaning) conducted at subcutaneous doses of 4.4, 13.3, & 40 mg/kg mg/kg/day, 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.

    Labor and Delivery


    SEE BOXED WARNING REGARDING OBSTETRlCAL USE OF 0.75% BUPIVACAINE HYDROCHLORIDE.

    Bupivacaine hydrochloride is contraindicated for obstetrical paracervical block anesthesia.

    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, Pharmacokinetics.) 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 central nervous system, peripheral vascular tone, and cardiac function.

    Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient’s legs and positioning her on her left side will help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable.

    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.

    Nursing Mothers


    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. Because of the potential for serious adverse reactions in nursing infants from bupivacaine, a decision should be made whether to discontinue nursing or not administer bupivacaine, taking into account the importance of the drug to the mother.

    Pediatric Use


    Until further experience is gained in pediatric patients younger than 12 years, administration of bupivacaine hydrochloride in this age group is not recommended. Continuous infusions of bupivacaine in children have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities. (See WARNINGS, PRECAUTIONS, and OVERDOSAGE. )

    Geriatric Use


    Patients over 65 years, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with bupivacaine hydrochloride. (See ADVERSE REACTIONS. )

    Elderly patients may require lower doses of bupivacaine hydrochloride. (See PRECAUTIONS, Epidural Anesthesiaand DOSAGE AND ADMINISTRATION. )

    In clinical studies, differences in various pharmacokinetic parameters have been observed between elderly and younger patients. (See CLINICAL PHARMACOLOGY.)

    This product is known to be substantially excreted by the kidney, and the risk of toxic 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. (See CLINICAL PHARMACOLOGY. )

  • ADVERSE REACTIONS


    Reactions to bupivacaine hydrochloride are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation.

    The most commonly encountered acute adverse experiences which demand immediate counter-measures are related to the central nervous system and the cardiovascular system. These adverse experiences are generally dose related and due to high plasma levels which may result from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) may result in underventilation or apnea (“Total or High Spinal”). Also, hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia may occur. This may lead to secondary cardiac arrest if untreated. Patients over 65 years, particularly those with hypertension, may be at increased risk for experiencing the hypotensive effects of bupivacaine hydrochloride. Factors influencing plasma protein binding, such as acidosis, systemic diseases which alter protein production, or competition of other drugs for protein binding sites, may diminish individual tolerance.

    Central Nervous System Reactions


    These are characterized by excitation and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Other central nervous system effects may be nausea, vomiting, chills, and constriction of the pupils.

    The incidence of convulsions associated with the use of local anesthetics varies with the procedure used and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1% of local anesthetic administrations.

    Cardiovascular System Reactions


    High doses or unintentional intravascular injection may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, heartblock, hypotension, bradycardia, ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, and cardiac arrest. (See WARNINGS, PRECAUTIONS, and OVERDOSAGE. )

    Allergic


    Allergic-type reactions are rare and may occur as a result of sensitivity to the local anesthetic. These reactions are characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and possibly, anaphylactoid-like symptomatology (including severe hypotension). Cross sensitivity among members of the amide-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitely established.

    Neurologic


    The incidences of adverse neurologic 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. Many of these effects may be related to local anesthetic techniques, with or without a contribution from the drug.

    In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter or needle may occur. Subsequent adverse effects may depend partially on the amount of drug administered intrathecally and the physiological and physical effects of a dural puncture. A high spinal is characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia.

    Neurologic effects following epidural or caudal anesthesia may include spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities and loss of sphincter control all of which may have slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; and cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid.

    Neurologic effects following other procedures or routes of administration may include persistent anesthesia, paresthesia, weakness, paralysis, all of which may have slow, incomplete, or no recovery.

  • OVERDOSAGE


    Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution. (See ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS. )

    Management of Local Anesthetic Emergencies


    The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered.

    The first step in the management of systemic toxic reactions, as well as underventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen with a delivery system capable of permitting immediate positive airway pressure by mask.
    This may prevent convulsions if they have not already occurred.

    If necessary, use drugs to control the convulsions. A 50 mg to 100 mg bolus IV injection of succinylcholine will paralyze the patient without depressing the central nervous or cardiovascular systems and facilitate ventilation. A bolus IV dose of 5 mg to 10 mg of diazepam or 50 mg to 100 mg of thiopental will permit ventilation and counteract central nervous system stimulation, but these drugs also depress central nervous system, respiratory, and cardiac function, add to postictal depression and may result in apnea. Intravenous barbiturates, anticonvulsant agents, or muscle relaxants should only be administered by those familiar with their use. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated. Supportive treatment of circulatory depression may require administration of intravenous fluids, and when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine or epinephrine to enhance myocardial contractile force).

    Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask if difficulty is encountered in the maintenance of a patent airway, or if prolonged ventilatory support (assisted or controlled) is indicated.

    Recent clinical data from patients experiencing local anesthetic-induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.

    If not treated immediately, convulsions with simultaneous hypoxia, hypercarbia, and acidosis plus myocardial depression from the direct effects of the local anesthetic may result in cardiac arrhythmias, bradycardia, asystole, ventricular fibrillation, or cardiac arrest. Respiratory abnormalities, including apnea, may occur. Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, successful outcome may require prolonged resuscitative efforts.

    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.

    The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 mg/kg to 8 mg/kg and 38 mg/kg to 54 mg/kg respectively.

  • DOSAGE AND ADMINISTRATION


    NOTE: The products accompanying this insert do not contain epinephrine.

    The dose of any local anesthetic administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient. The smallest dose and concentration required to produce the desired result should be administered. Dosages of bupivacaine hydrochloride injection should be reduced for elderly and/or debilitated patients and patients with cardiac and/or liver disease. The rapid injection of a large volume of local anesthetic solution should be avoided and fractional (incremental) doses should be used when feasible.

    For specific techniques and procedures, refer to standard textbooks.

    There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. Bupivacaine hydrochloride injection is not approved for this use (see WARNINGS and DOSAGE AND ADMINISTRATION).

    In recommended doses, bupivacaine hydrochloride produces complete sensory block, but the effect on motor function differs among the three concentrations.

    0.25% — when used for caudal, epidural, or peripheral nerve block, produces incomplete motor block. Should be used for operations in which muscle relaxation is not important, or when another means of providing muscle relaxation is used concurrently. Onset of action may be slower than with the 0.5% or 0.75% solutions.

    0.5% — provides motor blockade for caudal, epidural, or nerve block, but muscle relaxation may be inadequate for operations in which complete muscle relaxation is essential.

    0.75% — produces complete motor block. Most useful for epidural block in abdominal operations requiring complete muscle relaxation, and for retrobulbar anesthesia. Not for obstetrical anesthesia.

    The duration of anesthesia with bupivacaine hydrochloride injection is such that for most indications, a single dose is sufficient.

    Maximum dosage limit must be individualized in each case after evaluating the size and physical status of the patient, as well as the usual rate of systemic absorption from a particular injection site. Most experience to date is with single doses of bupivacaine hydrochloride injection up to 225 mg with epinephrine 1:200,000 and 175 mg without epinephrine; more or less drug may be used depending on individualization of each case.

    These doses may be repeated up to once every three hours. In clinical studies to date, total daily doses have been up to 400 mg. Until further experience is gained, this dose should not be exceeded in 24 hours. The duration of anesthetic effect may be prolonged by the addition of epinephrine.

    The dosages in Table 1 have generally proved satisfactory and are recommended as a guide for use in the average adult. These dosages should be reduced for elderly or debilitated patients. Until further experience is gained, bupivacaine hydrochloride injection is not recommended for pediatric patients younger than 12 years. Bupivacaine hydrochloride injection is contraindicated for obstetrical paracervical blocks, and is not recommended for intravenous regional anesthesia (Bier Block). 


    Use in Epidural Anesthesia


    During epidural administration of bupivacaine hydrochloride injection, 0.5% and 0.75% solutions should be administered in incremental doses of 3 mL to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. In obstetrics, only the 0.5% and 0.25% concentrations should be used; incremental doses of 3 mL to 5 mL of the 0.5% solution not exceeding 50 mg to 100 mg at any dosing interval are recommended. Repeat doses should be preceded by a test dose containing epinephrine if not contraindicated.

    Test Dose for Caudal and Lumbar Epidural Blocks


    See PRECAUTIONS

    Unused portions of solution should be discarded following initial use.

    This product should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Solutions which are discolored or which contain particulate matter should not be administered.


    Table 1. Recommended Concentrations and Doses of Bupivacaine Hydrochloride Injection
    Type of
    Block
    Conc.Each DoseMotor
    Block 1
    (mL)(mg)
    1With continuous (intermittent) techniques, repeat doses increase the degree of motor block. The first repeat dose of 0.5% may produce complete motor block. Intercostal nerve block with 0.25% may also produce complete motor block for intra-abdominal surgery.
    2 For single-dose use, not for intermittent epidural technique. Not for obstetrical anesthesia.
    3 See PRECAUTIONS.
    4 Solutions with or without epinephrine.
    Local
    infiltration
    0.25% 4
    up to
    max.
    up to
    max.
    ––
    Epidural
    0.75% 2,4
    10 to 20
    75 to 150
    complete
    0.5% 4
    10 to 20
    50 to 100
    moderate to complete
    0.25% 4
    10 to 20
    25 to 50
    partial to moderate
    Caudal
    0.5% 4
    15 to 30
    75 to 150
    moderate to complete
    0.25% 4
    15 to 30
    37.5 to 75
    moderate
    Peripheral
    nerves
    0.5% 4
    5 to max.
    25 to max.
    moderate to complete
    0.25% 4
    5 to max.
    12.5 to max.
    moderate to complete
    Retrobulbar 3
    0.75% 4
    2 to 4
    15 to 30
    complete
    Sympathetic
    0.25%
    20 to 50
    50 to 125

    Epidural 3
    Test Dose
    0.5%
    w/epi
    2 to 3
    10 to 15
    (10 to 15 micrograms
    epinephrine)
    ––
  • HOW SUPPLIED


    These solutions are not for spinal anesthesia.

    Bupivacaine Hydrochloride Injection, USP — Solution of Bupivacaine hydrochloride injection, USP may be autoclaved. Autoclave at 15-pound pressure, 121°C (250°F) for 15 minutes.

    Bupivacaine Hydrochloride Injection, USP is a clear, colorless, sterile isotonic solution and is available as follows:

    Bupivacaine Hydrochloride Injection, USP 0.25% (2.5 mg/mL)

    10 mL Single Dose Vials in a Carton of 25                                   NDC 55150-167-10
    30 mL Single Dose Vials in a Carton of 25                                   NDC 55150-168-30

    Bupivacaine Hydrochloride Injection, USP 0.5% (5 mg/mL)

    10 mL Single Dose Vials in a Carton of 25                                   NDC 55150-169-10
    30 mL Single Dose Vials in a Carton of 25                                   NDC 55150-170-30

    Bupivacaine Hydrochloride Injection, USP 0.75% (7.5 mg/mL)

    10 mL Single Dose Vials in a Carton of 25                                   NDC 55150-171-10
    30 mL Single Dose Vials in a Carton of 25                                   NDC 55150-172-30

    Store at
    20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

    This container closure is not made with natural rubber latex.

    Sterile, Nonpyrogenic

    Manufactured for:
    AuroMedics Pharma LLC
    6 Wheeling Road
    Dayton, NJ 08810

    Manufactured by:
    Aurobindo Pharma Limited
    IDA, Pashamylaram - 502307
    AP., India

    Issued: April 2013

  • SPL UNCLASSIFIED SECTION

    AQUEOUS SOLUTIONS FOR INFILTRATION

    AND NERVE BLOCK

    Ampul

    Plastic Multiple-dose Fliptop Vial

    Glass Teartop Vial

    Rx only

  • SPL UNCLASSIFIED SECTION

    Preservative-Free

    For Infiltration and Nerve Block

    Rx only

  • DESCRIPTION

    Lidocaine Hydrochloride Injections are sterile, nonpyrogenic, aqueous, isotonic solutions that contain a local anesthetic agent and are administered parenterally by injection. See  INDICATIONS AND USAGE   for specific uses.

    Each mL of the 1% solution contains lidocaine hydrochloride 10 mg and sodium chloride 7 mg. Each mL of the 2% solution contains lidocaine hydrochloride 20 mg and sodium chloride 6 mg. The pH of these solutions is adjusted to approximately 5.0 to 7.0 with sodium hydroxide and/or hydrochloric acid.

    Lidocaine Hydrochloride Injection solutions contain lidocaine hydrochloride which is chemically designated as acetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-, monohydrochloride and has the molecular wt. 270.8. Lidocaine HCl (C 14H 22N 2O • HCl) has the following structural formula:

    structure-1


  • CLINICAL PHARMACOLOGY

    Mechanism of Action

    Lidocaine HCl 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 HCl 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 HCl 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 HCl is protein bound.  Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

    Lidocaine HCl crosses the blood-brain and placental barriers, presumably by passive diffusion.

    Lidocaine HCl 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 HCl.  Approximately 90% of lidocaine HCl 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 HCl following an intravenous bolus injection is typically 1.5 to 2 hours.  Because of the rapid rate at which lidocaine HCl is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics.  The half-life may be prolonged two-fold or more in patients with liver dysfunction.  Renal dysfunction does not affect lidocaine HCl 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 HCl 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.

  • INDICATIONS AND USAGE

    Lidocaine HCl Injections are indicated for production of local or regional anesthesia by infiltration techniques such as percutaneous injection by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks, when the accepted procedures for these techniques as described in standard textbooks are observed. 

  • CONTRAINDICATIONS

    Lidocaine HCl is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.

  • WARNINGS

    LIDOCAINE HCl INJECTIONS FOR INFILTRATION AND NERVE BLOCK SHOULD BE EMPLOYED ONLY BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER ENSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT AND THE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (see also ADVERSE REACTIONS and PRECAUTIONS). 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.

    Intra-articular infusions of local anesthetics 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 glenohumeral 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 not associated with these findings. 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 2nd 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.

    To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

    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. If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.

    Signs and symptoms of methemoglobinemia may occur immediately or may be delayed some hours after exposure and are characterized by a cyanotic skin discoloration and abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue lidocaine and any other oxidizing agents. Depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

  • PRECAUTIONS

    General

    The safety and effectiveness of lidocaine HCl depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies.  Standard textbooks should be consulted for specific techniques and precautions for various regional anesthetic procedures.

    Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (see WARNINGS and ADVERSE REACTIONS).  The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects.  Syringe aspirations should also be performed before and during each supplemental injection when using indwelling catheter techniques.  During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and that the patient be monitored for central nervous system toxicity and cardiovascular toxicity, as well as for signs of unintended intrathecal administration, before proceeding.  When clinical conditions permit, consideration should be given to employing local anesthetic solutions that contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection.  An intravascular injection is still possible even if aspirations for blood are negative.  Repeated doses of lidocaine HCl may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites.  Tolerance to elevated blood levels varies with the status of the patient.  Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition.  Lidocaine HCl should also be used with caution in patients with severe shock or heart block.

    Lumbar and caudal epidural anesthesia should be used with extreme caution in persons with the following conditions: existing neurological disease, spinal deformities, septicemia, and severe hypertension.

    Local anesthetic solutions containing a vasoconstrictor should be used cautiously and in carefully circumscribed quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply.  Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response.  Ischemic injury or necrosis may result.  Preparations containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions.

    Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be accomplished after each local anesthetic injection.  It should be kept in mind at such times that restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness may be early warning signs of central nervous system toxicity.  

    Since amide-type local anesthetics are metabolized by the liver, Lidocaine HCl Injection should be used with caution in patients with hepatic disease.  Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations.  Lidocaine HCl Injection should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs.    

    Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia.  Since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available.  Early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation.  Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using).

    Proper tourniquet technique, as described in publications and standard textbooks, is essential in the performance of intravenous regional anesthesia.  Solutions containing epinephrine or other vasoconstrictors should not be used for this technique.

    Lidocaine HCl should be used with caution in persons with known drug sensitivities.  Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine HCl.

    Use in the Head and Neck Area

    Small doses of local anesthetics 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.  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.  Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed.  Resuscitative equipment and personnel for treating adverse reactions should be immediately available.  Dosage recommendations should not be exceeded (see DOSAGE AND ADMINISTRATION).

    Information for Patients

    When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of epidural anesthesia.

    Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to stop use and seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

    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.

    Patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents:

    Class

    Examples

    Nitrates/Nitrites

    nitroglycerin, nitroprusside, nitric oxide, nitrous oxide

    Local anesthetics

    benzocaine, lidocaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, articaine, ropivacaine

    Antineoplastic agents

    cyclophosphamide, flutamide, rasburicase, ifosfamide, hydroxyurea

    Antibiotics

    dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid

    Antimalarials

    chloroquine, primaquine

    Anticonvulsants

    phenytoin, sodium valproate, phenobarbital

    Other drugs

    acetaminophen, metoclopramide, sulfa drugs (i.e., sulfasalazine), quinine

    Drug/Laboratory Test Interactions

    The intramuscular injection of lidocaine HCl may result in an increase in creatine phosphokinase levels.  Thus, the use of this enzyme determination, without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromised by the intramuscular injection of lidocaine HCl.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Studies of lidocaine HCl in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility have not been conducted.

    Pregnancy

    Teratogenic Effects: Pregnancy Category B. 

    Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by lidocaine HCl.  There are, however, no adequate and well-controlled studies in pregnant women.  Animal reproduction studies are not always predictive of human response.  General consideration should be given to this fact before administering lidocaine HCl to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place.


    Labor and Delivery

    Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).  The potential for toxicity depends 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 central nervous system, peripheral vascular tone and cardiac function.

    Maternal hypotension has resulted from regional anesthesia.  Local anesthetics produce vasodilation by blocking sympathetic nerves.  Elevating the patient’s legs and positioning her on her left side will help prevent decreases in blood pressure.

    The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.

    Epidural, spinal, paracervical, or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts.  In one study, paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation.  However, spinal and epidural anesthesia have also 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.  The long-term significance of these observations is unknown.  Fetal bradycardia may occur in 20 to 30 percent of patients receiving paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated with fetal acidosis.  Fetal heart rate should always be monitored during paracervical anesthesia.  The physician should weigh the possible advantages against risks when considering a paracervical block in prematurity, toxemia of pregnancy, and fetal distress.  Careful adherence to recommended dosage is of the utmost importance in obstetrical paracervical block.  Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection.  Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both.  Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and often manifest seizures within six hours.  Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication.

    Case reports of maternal convulsions and cardiovascular collapse following use of some local anesthetics for paracervical block in early pregnancy (as anesthesia for elective abortion) suggest that systemic absorption under these circumstances may be rapid.  The recommended maximum dose of each drug should not be exceeded.  Injection should be made slowly and with frequent aspiration.  Allow a 5-minute interval between sides.

    Nursing Mothers

    It is not known whether this drug is excreted in human milk.  Because many drugs are excreted in human milk, caution should be exercised when lidocaine HCl is administered to a nursing woman.

    Pediatric Use

    Dosages in pediatric patients should be reduced, commensurate with age, body weight and physical condition (see DOSAGE AND ADMINISTRATION).

  • ADVERSE REACTIONS

    Systemic

    Adverse experiences following the administration of lidocaine HCl 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 HCl 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 as a result of sensitivity to lidocaine HCl are extremely rare and, if they occur, should be managed by conventional means.  The detection of sensitivity by skin testing is of doubtful value.

    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 HCl 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.

  • OVERDOSAGE

    Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (see ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS).

    Management of Local Anesthetic Emergencies

    The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection.  At the first sign of change, oxygen should be administered.

    The first step in the management of convulsions, as well as underventilation or apnea due to unintended subarachnoid injection of drug solution, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask.  Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously.  Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously.  The clinician should be familiar, prior to the use of local anesthetics, with these anticonvulsant drugs.  Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor as directed by the clinical situation (eg, ephedrine).

    If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest.  Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted.  If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.

    Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated.

    Dialysis is of negligible value in the treatment of acute overdosage with lidocaine HCl.

    The oral LD 50 of lidocaine HCl in non-fasted female rats is 459 (346 to 773) mg/kg (as the salt) and 214 (159 to 324) mg/kg (as the salt) in fasted female rats.

  • DOSAGE AND ADMINISTRATION

    Table 1 (Recommended Dosages) summarizes the recommended volumes and concentrations of Lidocaine HCl Injection for various types of anesthetic procedures.  The dosages suggested in this table are for normal healthy adults and refer to the use of epinephrine-free solutions.  When larger volumes are required, only solutions containing epinephrine should be used except in those cases where vasopressor drugs may be contraindicated.

    There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures.  Lidocaine HCl Injection is not approved for this use (see WARNINGS and DOSAGE AND ADMINISTRATION).

    These recommended doses serve only as a guide to the amount of anesthetic required for most routine procedures.  The actual volumes and concentrations to be used depend on a number of factors such as type and extent of surgical procedure, depth of anesthesia and degree of muscular relaxation required, duration of anesthesia required, and the physical condition of the patient.  In all cases the lowest concentration and smallest dose that will produce the desired result should be given.  Dosages should be reduced for children and for the elderly and debilitated patients and patients with cardiac and/or liver disease.

    The onset of anesthesia, the duration of anesthesia and the degree of muscular relaxation are proportional to the volume and concentration (ie, total dose) of local anesthetic used.  Thus, an increase in volume and concentration of Lidocaine HCl Injection will decrease the onset of anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and increase the segmental spread of anesthesia.  However, increasing the volume and concentration of Lidocaine HCl Injection may result in a more profound fall in blood pressure when used in epidural anesthesia.  Although the incidence of side effects with lidocaine HCl is quite low, caution should be exercised when employing large volumes and concentrations, since the incidence of side effects is directly proportional to the total dose of local anesthetic agent injected.

    Epidural Anesthesia

    For epidural anesthesia, only the following dosage forms of Lidocaine HCl Injection are recommended:

    1% without epinephrine                         5 mL Preservative-Free vials

    2% without epinephrine                         5 mL Preservative-Free vials

    Although these solutions are intended specifically for epidural anesthesia, they may also be used for infiltration and peripheral nerve block, provided they are employed as single dose units.  These solutions contain no bacteriostatic agent. 

    In epidural anesthesia, the dosage varies with the number of dermatomes to be anesthetized (generally 2 to 3 mL of the indicated concentration per dermatome).

    Caudal and Lumbar Epidural Block

    As a precaution against the adverse experience sometimes observed following unintentional penetration of the subarachnoid space, a test dose such as 2 to 3 mL of 1.5% lidocaine HCl should be administered at least 5 minutes prior to injecting the total volume required for a lumbar or caudal epidural block.  The test dose should be repeated if the patient is moved in a manner that may have displaced the catheter.  Epinephrine, if contained in the test dose (10 to 15 mcg have been suggested), may serve as a warning of unintentional intravascular injection.  If injected into a blood vessel, this amount of epinephrine is likely to produce a transient “epinephrine response” within 45 seconds, consisting of an increase in heart rate and 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.  Patients on beta blockers may not manifest changes in heart rate, but blood pressure monitoring can detect an evanescent rise in systolic blood pressure.  Adequate time should be allowed for onset of anesthesia after administration of each test dose.  The rapid injection of a large volume of Lidocaine HCl Injection through the catheter should be avoided, and, when feasible, fractional doses should be administered.

    In the event of the known injection of a large volume of local anesthetic solution into the subarachnoid space, after suitable resuscitation and if the catheter is in place, consider attempting the recovery of drug by draining a moderate amount of cerebrospinal fluid (such as 10 mL) through the epidural catheter.

  • MAXIMUM RECOMMENDED DOSAGES

    NOTE: The products accompanying this insert do not contain epinephrine.

    Adults

    For normal healthy adults, the individual maximum recommended dose of lidocaine HCl with epinephrine should not exceed 7 mg/kg (3.5 mg/lb) of body weight, and in general it is recommended that the maximum total dose not exceed 500 mg.  When used without epinephrine the maximum individual dose should not exceed 4.5 mg/kg (2 mg/lb) of body weight, and in general it is recommended that the maximum total dose does not exceed 300 mg.  For continuous epidural or caudal anesthesia, the maximum recommended dosage should not be administered at intervals of less than 90 minutes.  When continuous lumbar or caudal epidural anesthesia is used for non-obstetrical procedures, more drug may be administered if required to produce adequate anesthesia.

    The maximum recommended dose per 90 minute period of lidocaine hydrochloride for paracervical block in obstetrical patients and non-obstetrical patients is 200 mg total.  One half of the total dose is usually administered to each side. Inject slowly, five minutes between sides (see also discussion of paracervical block in PRECAUTIONS).

    Pediatric Patients

    It is difficult to recommend a maximum dose of any drug for pediatric patients, since this varies as a function of age and weight.  For children over 3 years of age who have a normal lean body mass and normal body development, the maximum dose is determined by the child’s age and weight.  For example, in a child of 5 years weighing 50 lbs the dose of lidocaine HCl should not exceed 75 to 100 mg (1.5 to 2 mg/lb).  The use of even more dilute solutions (ie, 0.25 to 0.5%) and total dosages not to exceed 3 mg/kg (1.4 mg/lb) are recommended for induction of intravenous regional anesthesia in pediatric patients.

    In order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose should be used at all times.  In some cases it will be necessary to dilute available concentrations with 0.9% sodium chloride injection in order to obtain the required final concentration.

    NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit.  The injection is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.

    Table 1. Recommended Dosages



    Procedure

    Lidocaine Hydrochloride
    Injection without epinephrine

    Conc (%)

    Vol (mL)

    Total Dose (mg)

    Infiltration




       Percutaneous

    0.5 or 1

    1 to 60

    5 to 300

    Peripheral Nerve Blocks, eg.




       Brachial

    1.5

    15 to 20

    225 to 300

       Dental

    2

    1 to 5

    20 to 100

       Intercostal

    1

    3

    30

       Paravertebral

    1

    3 to 5

    30 to 50

       Pudendal (each side)

    1

    10

    100

    Paracervical




       Obstetrical analgesia (each side)


    1

    10

    100

    Sympathetic Nerve Blocks, eg,




       Cervical (stellate ganglion)

    1

    5

    50

       Lumbar

    1

    5 to 10

    50 to 100

    Central Neural Blocks




       Epidural*




          Thoracic

    1

    20 to 30

    200 to 300

          Lumbar




             Analgesia

    1

    25 to 30

    250 to 300

             Anesthesia

    1.5

    15 to 20

    225 to 300


    2

    10 to 15

    200 to 300

    Caudal




       Obstetrical analgesia

    1

    20 to 30

    200 to 300

       Surgical anesthesia

    1.5

    15 to 20

    225 to 300

    *Dose determined by number of dermatomes to be anesthetized (2 to 3 mL/dermatome).

    THE ABOVE SUGGESTED CONCENTRATIONS AND VOLUMES SERVE ONLY AS A GUIDE. OTHER VOLUMES AND CONCENTRATIONS MAY BE USED PROVIDED THE TOTAL MAXIMUM RECOMMENDED DOSE IS NOT EXCEEDED.

  • STERILIZATION, STORAGE AND TECHNICAL PROCEDURES

    Disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc) should not be used for skin or mucous membrane disinfection as they have been related to incidents of swelling and edema. 

  • HOW SUPPLIED

    Lidocaine Hydrochloride Injection, USP is available as:

    Preservative-Free

    1% (50 mg/5 mL) (10 mg /mL)

        5 mL Single Dose Vials packaged in 25s ( NDC 0143-9595-25)

    2% (100 mg/5 mL) (20 mg /mL)

        5 mL Single Dose Vials packaged in 25s ( NDC 0143-9594-25)

    Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].   

    To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    For Product Inquiry call 1-877-845-0689.

  • SPL UNCLASSIFIED SECTION

    Manufactured by
    HIKMA FARMACÊUTICA (PORTUGAL), S.A.
    Estrada do Rio da Mό, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL

    Distributed by
    WEST-WARD
    A HIKMA COMPANY
    Eatontown, NJ 07724 USA

    August 2016

    PIN363-WES/1

  • ACTIVE INGREDIENT

    Section Text

    Active Ingredient                                  Purpose

    Povidone Iodine 10% v/v                        Antiseptic                          

  • Uses:


    Section Text

    • First aid antiseptic to help prevent skin infection in minor cuts, scrapes and burns.
    • For preparation of the skin prior to surgery.
    • Helps reduce bacteria that can potentially cause skin infections.
  • Warnings:

    Section Text

    • FOR EXTERNAL USE ONLY
  • Do not use:


    • As a first aid antiseptic for more than 1 week.
    • In the eyes.
    • Over large areas of the body.
  • Ask a doctor before use if you have:


    • Deep puncture wounds
    • Animal bites
    • Serious burns
  • Stop Use:


    • If irritation and redness develop
    • If condition persists for more than 72 hours, consult a physician.
  • Keep Out Of Reach Of Children

    Keep out of reach of children.If swallowed, get medical help or contact a Poison Control Center.


  • Directions Povidone iodine:

    Tear at notch, remove applicator, use only once.

    As a first aid antiseptic

    • clean affected area
    • apply 1 to 3 times daily
    • may be covered with a sterile bandage, if bandaged let dry.

    For preoperative patient skin preparation

    • clean area
    • apply to operative site prior to surgery using the applicator


  • Other information:

    Store at room temperature.

    Avoid excessive heat

  • INDICATIONS & USAGE

    For use as an

    • first aid antiseptic
    • pre-operative skin preperation
  • Inactive Ingredients

    Inactive ingredients: nonoxynol-9, water

  • PRINCIPAL DISPLAY PANEL

    NDC: 76420-730-01 Rx Only

    Marlido Kit™

    Kit Contains

    1 Bupivacaine HCl 0.5% Single Dose Vial (10mL)

    1 Lidocaine HCl Injection, USP 2% (5mL)

    1 Povidone-Iodine Swabsticks (3 Swabs)

    1 Pair Nitrile Powder Free Sterile Gloves (M)

    1 Drape

    1 Adhesive Bandage

    5 Non Sterile 4x4 Gauze

    Needles and Syringes Not Included

    1 Dose

    Single Use Only

    Distributed by
    Enovachem™
    PHARMACEUTICALS
    Torrance, CA 90501

    Figure
  • INGREDIENTS AND APPEARANCE
    MARLIDO KIT 
    marcaine, lidocaine, povidone iodine kit
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:76420-730
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:76420-730-011 in 1 CARTON; Type 1: Convenience Kit of Co-Package05/23/2016
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 11 VIAL, SINGLE-DOSE 10 mL
    Part 21 VIAL 5 mL
    Part 31 PACKET 0.9 mL
    Part 1 of 3
    BUPIVACAINE HYDROCHLORIDE 
    bupivacaine hydrochloride injection, solution
    Product Information
    Route of AdministrationEPIDURAL, INFILTRATION
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    BUPIVACAINE HYDROCHLORIDE (UNII: 7TQO7W3VT8) (BUPIVACAINE - UNII:Y8335394RO) BUPIVACAINE HYDROCHLORIDE ANHYDROUS5 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    110 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA01696405/04/2010
    Part 2 of 3
    LIDOCAINE HYDROCHLORIDE 
    lidocaine hydrochloride injection, solution
    Product Information
    Route of AdministrationEPIDURAL, INFILTRATION
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    LIDOCAINE HYDROCHLORIDE (UNII: V13007Z41A) (LIDOCAINE - UNII:98PI200987) LIDOCAINE HYDROCHLORIDE ANHYDROUS20 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    15 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA08829403/30/2010
    Part 3 of 3
    POVIDINE IODINE 
    povidine iodine swab
    Product Information
    Item Code (Source)NDC:67777-130
    Route of AdministrationTOPICAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    POVIDONE-IODINE (UNII: 85H0HZU99M) (IODINE - UNII:9679TC07X4) IODINE10 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    NONOXYNOL-9 (UNII: 48Q180SH9T)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    10.9 mL in 1 PACKET; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    OTC monograph finalpart333C05/10/2010
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    unapproved drug other02/04/2014
    Labeler - Asclemed USA, Inc. (059888437)