Product Elements:
Bupivacaine hydrochloride bupivacaine hydrochloride dextrose sodium hydroxide hydrochloric acid water nitrogen bupivacaine hydrochloride bupivacaine bupivacaine hydrochloride anhydrous
Indications and Usage:
Indications and usage: bupivacaine hydrochloride in dextrose injection, usp is indicated for the production of subarachnoid block (spinal anesthesia). standard textbooks should be consulted to determine the accepted procedures and techniques for the administration of spinal anesthesia.
Warnings:
Warnings: 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 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. 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 un
Read more...der 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 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 central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. discontinue bupivacaine hydrochloride in dextrose injection, usp and 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. 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 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. spinal anesthetics should not be injected during uterine contractions, because spinal fluid current may carry the drug further cephalad than desired. a free flow of cerebrospinal fluid during the performance of spinal anesthesia is indicative of entry into the subarachnoid space. however, aspiration should be performed before the anesthetic solution is injected to confirm entry into the subarachnoid space and to avoid intravascular injection. bupivacaine hydrochloride in dextrose injection, usp solutions containing epinephrine or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur. likewise, solutions of bupivacaine hydrochloride in dextrose injection, usp containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamine oxidase inhibitors (maoi) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result. until further experience is gained in patients younger than 18 years, administration of bupivacaine hydrochloride in dextrose injection, usp in this age group is not recommended. mixing or the prior or intercurrent use of any other local anesthetic with bupivacaine hydrochloride in dextrose injection, usp cannot be recommended because of insufficient data on the clinical use of such mixtures.
Dosage and Administration:
Dosage and administration 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 in dextrose injection, usp should be reduced for elderly and debilitated patients and patients with cardiac and/or liver disease. 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 in dextrose injection, usp is not approved for this use (see warnings and dos
Read more...age and administration ). the extent and degree of spinal anesthesia depend upon several factors including dosage, specific gravity of the anesthetic solution, volume of solution used, force of injection, level of puncture, and position of the patient during and immediately after injection. seven and one-half mg (7.5 mg or 1 ml) bupivacaine hydrochloride in dextrose injection, usp has generally proven satisfactory for spinal anesthesia for lower extremity and perineal procedures including turp and vaginal hysterectomy. twelve mg (12 mg or 1.6 ml) has been used for lower abdominal procedures such as abdominal hysterectomy, tubal ligation, and appendectomy. these doses are recommended as a guide for use in the average adult and may be reduced for the elderly or debilitated patients. because experience with bupivacaine hydrochloride in dextrose injection, usp is limited in patients below the age of 18 years, dosage recommendations in this age group cannot be made. obstetrical use : doses as low as 6 mg bupivacaine hydrochloride have been used for vaginal delivery under spinal anesthesia. the dose range of 7.5 mg to 10.5 mg (1 ml to 1.4 ml) bupivacaine hydrochloride has been used for cesarean section under spinal anesthesia. in recommended doses, bupivacaine hydrochloride in dextrose injection, usp produces complete motor and sensory block. unused portions of solutions should be discarded following initial use. bupivacaine hydrochloride in dextrose injection, usp should be inspected visually for discoloration and particulate matter prior to administration; solutions which are discolored or which contain particulate matter should not be administered.
Contraindications:
Contraindications: bupivacaine hydrochloride in dextrose injection, usp is contraindicated in patients with a known hypersensitivity to it or to any local anesthetic agent of the amide-type. the following conditions preclude the use of spinal anesthesia: severe hemorrhage, severe hypotension or shock and arrhythmias, such as complete heart block, which severely restrict cardiac output. local infection at the site of proposed lumbar puncture. septicemia.
Adverse Reactions:
Adverse reactions reactions to bupivacaine are characteristic of those associated with other amide-type local anesthetics. the most commonly encountered acute adverse experiences which demand immediate countermeasures following the administration of spinal anesthesia are hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia. these may lead to cardiac arrest if untreated. in addition, dose-related convulsions and cardiovascular collapse may result from diminished tolerance, rapid absorption from the injection site, or from unintentional intravascular injection of a local anesthetic solution. 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. respiratory system : respiratory paralysis or underventilation may be noted as a result of upward exten
Read more...sion of the level of spinal anesthesia and may lead to secondary hypoxic cardiac arrest if untreated. preanesthetic medication, intraoperative analgesics and sedatives, as well as surgical manipulation, may contribute to underventilation. this will usually be noted within minutes of the injection of spinal anesthetic solution, but because of differing maximal onset times, differing intercurrent drug usage and differing surgical manipulation, it may occur at any time during surgery or the immediate recovery period. cardiovascular system : hypotension due to loss of sympathetic tone is a commonly encountered extension of the clinical pharmacology of spinal anesthesia. this is more commonly observed in elderly patients, particularly those with hypertension, and patients with shrunken blood volume, shrunken interstitial fluid volume, cephalad spread of the local anesthetic, and/or mechanical obstruction of venous return. nausea and vomiting are frequently associated with hypotensive episodes following the administration of spinal anesthesia. high doses, or inadvertent intravascular injection, may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, bradycardia, heart block, ventricular arrhythmias, and, possibly, cardiac arrest (see warnings , precautions , and overdosage sections). cns : respiratory paralysis or underventilation secondary to cephalad spread of the level of spinal anesthesia (see respiratory system ) and hypotension for the same reason (see cardiovascular system) are the two most commonly encountered cns-related adverse observations which demand immediate countermeasures. high doses or inadvertent intravascular injection may lead to high plasma levels and related cns toxicity characterized by excitement 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. 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. neurologic effects following spinal anesthesia may include loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness and paralysis of the lower extremities, and loss of sphincter control all of which may have slow, incomplete, or no recovery; hypotension, high or total spinal block; urinary retention; headache; backache; septic meningitis, meningismus; arachnoiditis; slowing of labor; increased incidence of forceps delivery; shivering; cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid; and fecal and urinary incontinence. 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. other : nausea and vomiting may occur during spinal anesthesia.
Overdosage:
Overdosage acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use or to underventilation (and perhaps apnea) secondary to upward extension of spinal anesthesia. hypotension is commonly encountered during the conduct of spinal anesthesia due to relaxation of sympathetic tone, and sometimes, contributory mechanical obstruction of venous return. 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 patientâs 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 a high or total spinal, 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 intravenous injection of succinylcholine will paralyze the patient without depressing the central nervous or cardiovascular systems and facilitate ventilation. a bolus intravenous dose of 5 mg to 10 mg of diazepam or 50 mg to 100 mg of thiopental will permit ventilation and counteract cns stimulation, but these drugs also depress cns, 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). hypotension due to sympathetic relaxation may be managed by giving intravenous fluids (such as isotonic saline or lactated ringerâs solution), in an attempt to relieve mechanical obstruction of venous return, or by using vasopressors (such as ephedrine which increases the force of myocardial contractions) and, if indicated, by giving plasma expanders or whole blood. 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 a high or total spinal 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 and maintained for a prolonged period if necessary. recovery has been reported after 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.
Description:
Description: bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl- n -(2,6-dimethylphenyl)-, monohydrochloride, monohydrate, a white 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: dextrose is d-glucopyranose monohydrate and has the following structural formula: bupivacaine hydrochloride in dextrose injection, usp is available in sterile hyperbaric solution for subarachnoid injection (spinal block). bupivacaine hydrochloride 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. each ml of bupivacaine hydrochloride in dextrose injection, usp contains 7.5 mg bupivacaine hydrochloride (anhydrous) and 82.5 mg dextrose (anhydrous). the ph of this solution is adjusted to between 4.0 and 6.5 with sodium hydroxide or hydrochloric acid. the specific gravity of bupivacaine hydrochloride in dextrose injection, usp is between 1.030 and 1.035 at 25°c and 1.03 at 37°c. bupivacaine hydrochloride in dextrose injection, usp does not contain any preservatives. bupivacaine formula dextrose formula
Clinical Pharmacology:
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, vent
Read more...ricular 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 direct intravascular injection of bupivacaine. therefore, when epidural anesthesia with bupivacaine is considered, incremental dosing is necessary. following systemic absorption, local anesthetics can produce cns 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 stage. pharmacokinetics: âthe 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 hydrochloride in dextrose injection, usp, permitting the use of moderately larger total doses and sometimes prolonging the duration of action. the onset of action with bupivacaine hydrochloride in dextrose injection, usp is rapid and anesthesia is long lasting. the duration of anesthesia is significantly longer with bupivacaine hydrochloride in dextrose injection, usp 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. the onset of sensory blockade following spinal block with bupivacaine hydrochloride in dextrose injection, usp is very rapid (within one minute); maximum motor blockade and maximum dermatome level are achieved within 15 minutes in most cases. duration of sensory blockade (time to return of complete sensation in the operative site or regression of two dermatomes) following a 12 mg dose averages 2 hours with or without 0.2 mg epinephrine. the time to return of complete motor ability with 12 mg bupivacaine hydrochloride in dextrose injection, usp averages 3 1/2 hours without the addition of epinephrine and 4 1/2 hours if 0.2 mg epinephrine is added. when compared to equal milligram doses of hyperbaric tetracaine, the duration of sensory blockade was the same but the time to complete motor recovery was significantly longer for tetracaine. addition of 0.2 mg epinephrine significantly prolongs the motor blockade and time to first postoperative narcotic with bupivacaine hydrochloride in dextrose injection, usp. 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 hydrochloride in dextrose injection, usp 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 profiles of bupivacaine hydrochloride in dextrose injection, usp 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. 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 hydrochloride in dextrose injection, usp in adults is 2.7 hours and in neonates 8.1 hours. in clinical studies, elderly patients exhibited a greater spread and higher maximal level of analgesia than younger patients. elderly patients also reached the maximal level of analgesia more rapidly than younger patients, and exhibited a faster onset of motor blockade. the total plasma clearance was decreased and the terminal half-life was lengthened in these patients. amide-type local anesthetics such as bupivacaine hydrochloride in dextrose injection, usp 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. pipecolylxylidine is the major metabolite of bupivacaine hydrochloride in dextrose injection, usp. 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 in dextrose injection, usp does not ordinarily produce irritation or tissue damage
How Supplied:
How supplied single-dose ampules of 2 ml (15 mg bupivacaine hydrochloride with 165 mg dextrose), is supplied as follows: ndc container concentration size total (mg) 73293-0002-2 single dose ampule (package of 50) 0.75% (7.5 mg/ml) 2 ml 15 store at 20° to 25°c (68° to 77°f); excursions permitted between 15° to 30°c (59° to 86°f). [see usp controlled room temperature.] bupivacaine hydrochloride in dextrose injection, usp solution may be autoclaved once at 15 pound pressure, 121°c (250°f) for 15 minutes. do not administer any solution which is discolored or contains particulate matter. for single-dose ampules: discard the unused portion. manufactured by: huons co., ltd., 100, bio valley-ro, jecheon-si, chungcheongbuk-do, 27159, republic of korea product code: 0002 revised: 03/2020
Package Label Principal Display Panel:
Principal display panel 2 ml (50 ampules unit dose) carton label 50 x 2 ml single-dose ampules ndc 73293-0002-2 sterile hyperbaric solution for spinal anesthesia bupivacaine hydrochloride in 8.25% dextrose injection, usp spinal 0.75% (15 mg/2 ml) (7.5 mg/ml) huons 2 ml ampule label 2 ml ampule ndc 73293-0002-1 el5936-03 rx only bupivacaine hcl 0.75% in dextrose 8.25% injection, usp spinal contains 7.5 mg bupivacaine hcl (anhydrous) and 82.5 mg dextrose (anhydrous) per ml. ph adjusted between 4.0 and 6.5 with naoh or hcl. huons co., ltd. lot no. : xxxxxx exp. date : mm/yyyy carton label ampule label