^Indications & Usage
A. FOR INTRAMUSCULAR ADMINISTRATION When oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, the intramuscular use of Methylprednisolone acetate Sterile Aqueous Suspension is indicated as follows:
Allergic States:Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, serum sickness, transfusion reactions.
Dermatologic Diseases:Bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, pemphigus, severe erythema multiforme (Stevens-Johnson syndrome).
Endocrine Disorders:Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance), congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsuppurative thyroiditis.
Gastrointestinal Diseases: To tide the patient over a critical period of the disease in regional enteritis (systemic therapy) and ulcerative colitis.
Hematologic Disorders:Acquired (autoimmune) hemolytic anemia, congenital (erythroid) hypoplastic anemia (Diamond Blackfan anemia), pure red cell aplasia, select cases of secondary thrombocytopenia. Miscellaneous:Trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.
Neoplastic Diseases:For palliative management of leukemias and lymphomas.
Nervous System: Cerebral edema associated with primary or metastatic brain tumor or craniotomy.
Ophthalmic Diseases: Sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids.
Renal Diseases:To induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome, or that due to lupus erythematosus.
Respiratory Diseases:Berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis.
Rheumatic Disorders: As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis; acute rheumatic carditis; ankylosing spondylitis; psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy). For the treatment of dermatomyositis, polymyositis, and systemic lupus erythematosus.
B. FOR INTRA-ARTICULAR OR SOFT TISSUE ADMINISTRATION (See WARNINGS) Methylprednisolone acetate injectable suspension is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis of osteoarthritis.
C. FOR INTRALESIONAL ADMINISTRATION Methylprednisolone acetate injectable suspension is indicated for intralesional use in alopecia areata, discoid lupus erythematosus, keloids, localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis), and psoriatic plaques, necrobiosis lipoidica diabeticorum. Methylprednisolone acetate injectable suspension also may be useful in cystic tumors of an aponeurosis or tendon (ganglia).
^Keep Out Of Reach Of Children.
If swallowed, get medical assistance or immediately contact a Poison Control Center.
^ Description
Bupivacaine Hydrochloride Injection contains bupivacaine hydrochloride, an amide local anesthetic, as the active pharmaceutical ingredient. The route of administration for Bupivacaine Hydrochloride Injection is by injection, for infiltration, perineural, caudal, epidural, or retrobulbar use. [see Warnings and Precautions (5.4)] .
Bupivacaine hydrochloride is 2-piperidinecarboxamide, 1-butyl- N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate. It is 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:
Bupivacaine Hydrochloride Injection, USP is a clear and colorless sterile isotonic solution. Each mL of single-dose vial contains 5 mg of bupivacaine hydrochloride (equivalent to 4.44 mg of bupivacaine, respectively), sodium chloride for isotonicity, sodium hydroxide or hydrochloric acid to adjust the pH between 4 and 6.5, in water for injection.
^Pediatric Use
This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product ordinarily delivers amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the hepatic capacity to detoxify the chemical. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources. The efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids, which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephritic syndrome (patients >2 years of age) and aggressive lymphomas and leukemias (patients >1 month of age). Other indications for pediatric use of corticosteroids (e.g., severe asthma and wheezing) are based on adequate and well-controlled clinical trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations.
The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS ). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of HPA axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives. In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.
^Warning: Risk Of Cardiac Arrest With Use Of Bupivacaine Hydrochloride Injection In Obstetrical Anesthesia
There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration of Bupivacaine Hydrochloride Injection is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary [see Warnings and Precautions (5.1)].
^ Hepatic Impairment
Amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. Patients with severe hepatic impairment, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Therefore, consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with moderate to severe hepatic impairment treated with Bupivacaine Hydrochloride Injection, especially with repeat doses [see Warnings and Precautions (5.10)] .
^Drug Interactions
Aminoglutethimide:Aminoglutethimide may lead to a loss of corticosteroid- induced adrenal suppression.
Amphotericin B injection and potassium-depleting agents:When corticosteroids are administered concomitantly with potassium-depleting agents (e.g., amphotericin B, diuretics), patients should be observed closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.
Antibiotics:Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS: Drug Interactions , Hepatic Enzyme Inhibitors).
Anticholinesterases:Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.
Anticoagulants, oral: Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.
Antidiabetics: Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.
Antitubercular drugs: Serum concentrations of isoniazid may be decreased. Cholestyramine: Cholestyramine may increase the clearance of oral corticosteroids.
Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with concurrent use.
Digitalis glycosides: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.
Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.
Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin):Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased.
Hepatic Enzyme Inhibitors( e.g., ketoconazole, macrolide antibiotics such as erythromycin and troleandomycin): Drugs which inhibit cytochrome P450 3A4 have the potential to result in increased plasma concentrations of corticosteroids.
Ketoconazole: Ketoconazole has been reported to significantly decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects.
Nonsteroidal anti-inflammatory drugs (NSAIDs):Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with concurrent use of corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.
Skin Tests: Corticosteroids may suppress reactions to skin tests.
Vaccines: Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or attenuated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infections, Vaccinations ).
^ Potent Inhalation Anesthetics
Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine are used in patients during or following the administration of potent inhalation anesthetics.
^ Recommended Concentrations And Dosages Of Bupivacaine Hydrochloride Injection
The dosage of Bupivacaine Hydrochloride Injection 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. Administer the smallest dosage and concentration required to produce the desired result.
The types of block and recommended Bupivacaine Hydrochloride Injection concentrations are shown in Table 1.
Table 1. Types of Block and Recommended Bupivacaine Hydrochloride Injection Concentrations
* Bupivacaine Hydrochloride injection 0.75% (7.5 mg/mL) is not recommended for nonobstetrical surgical procedures in pregnant patients.
✓= indicated use [see Warnings and Precautions (5.1)].
At recommended dosages, Bupivacaine Hydrochloride produces complete sensory block, but the effect on motor function differs among the three concentrations. Table 2 provides information on the expected effect on motor function for the three concentrations.
The duration of anesthesia with Bupivacaine Hydrochloride Injection is such that for most indications, a single dose is sufficient.
The maximum dosage limit within the recommended dosage range must be individualized in each case after evaluating the size and physical status of the patient, as well as the anticipated rate of systemic absorption from a particular injection site.
The dosages in Table 3 are recommended as a guide for use in the average adult. These doses may be repeated once every three hours. Do not exceed a total daily dosage of 400 mg in 24 hours. The duration of anesthetic effect may be prolonged by the addition of epinephrine.
^4 Contraindications
Bupivacaine Hydrochloride Injection is contraindicated in:
^Inactive Ingredients
citric acid, disodium phosphate, water
^ Risk Of Respiratory Arrest With Use In Ophthalmic Surgery
Clinicians who perform retrobulbar blocks should be aware that there have been reports of respiratory arrest following local anesthetic injection. Prior to retrobulbar block (e.g., with Bupivacaine Hydrochloride Injection), as with all other regional procedures, resuscitative equipment and drugs, and personnel to manage respiratory arrest or depression, convulsions, and cardiac stimulation or depression should be immediately available [see Warnings and Precautions (5.14)]. As with other anesthetic procedures, patients should be constantly monitored following ophthalmic blocks for signs of these adverse reactions, which may occur following relatively low total doses.
A concentration of 0.75% bupivacaine is indicated for retrobulbar block; however, this concentration is not indicated for any other peripheral nerve block, including the facial nerve, and not indicated for local infiltration, including the conjunctiva [see Indications and Usage (1)].
^Overdosage
Treatment of acute overdosage is by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of the corticosteroid may be reduced only temporarily, or alternate day treatment may be introduced.
^Active Ingredient
Povidone-Iodine, 10% w/w
^ Risk Of Toxicity In Patients With Hepatic Impairment
Because amide local anesthetics such as bupivacaine are metabolized by the liver, consider reduced dosing and increased monitoring for bupivacaine systemic toxicity in patients with moderate to severe hepatic impairment who are treated with Bupivacaine Hydrochloride Injection, especially with repeat doses [see Use in Specific Populations (8.6)].
^ Risk Of Inadvertent Trauma To Tongue, Lips, And Buccal Mucosa In Dental Applications
Because of the long duration of anesthesia, when Bupivacaine Hydrochloride injection with epinephrine [0.5% (5 mg/mL) of bupivacaine] is used for dental injections, warn patients about the possibility of inadvertent trauma to tongue, lips, and buccal mucosa and advise them not to chew solid foods until sensation returns [see Patient Counseling Information (17)] .
^Other Information
^Adverse Reactions
The following adverse reactions have been reported with Methylprednisolone acetate injectable suspension or other corticosteroids: Allergic reactions : Allergic or hypersensitivity reactions, anaphylactoid reaction, anaphylaxis, angioedema.
Blood and lymphatic system disorders : Leukocytosis.
Cardiovascular : Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS ), pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.
Dermatologic : Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.
Endocrine : Decreased carbohydrate and glucose tolerance, development of cushingoid state, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.
Fluid and electrolyte disturbances : Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention.
Gastrointestinal : Abdominal distention, bowel/bladder dysfunction (after intrathecal administration), elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible subsequent perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis.
Metabolic : Negative nitrogen balance due to protein catabolism.
Musculoskeletal : Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, postinjection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.
Neurologic/Psychiatric : Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo. Ophthalmic : Exophthalmoses, glaucoma, increased intraocular pressure, posterior subcapsular cataracts.
Other : Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, injection site infections following non-sterile administration (see WARNINGS ), malaise, moon face, weight gain.
The following adverse reactions have been reported with the following routes of administration:
Intrathecal/Epidural : Arachnoiditis, bowel/bladder dysfunction, headache, meningitis, parapareisis/paraplegia, seizures, sensory disturbances.
Intranasal : Allergic reactions, rhinitis, temporary/permanent visual impairment including blindness.
Ophthalmic : Increased intraocular pressure, infection, ocular and periocular inflammation including allergic reactions, residue or slough at injection site, temporary/permanent visual impairment including blindness.
Miscellaneous injection sites ( scalp, tonsillar fauces, sphenopalatine ganglion): Blindness. To report SUSPECTED ADVERSE REACTIONS, contact Slayback Pharma at 1-844-566-2505 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
^ Risk Of Systemic Toxicities With Unintended Intravascular Or Intrathecal Injection
Unintended intravascular or intrathecal injection of Bupivacaine Hydrochloride Injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progressing ultimately to respiratory arrest. Unintentional intrathecal injection during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column has resulted in underventilation or apnea ("Total or High Spinal"). A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia [see Adverse Reactions (6)] .
Aspirate for blood or cerebrospinal fluid (where applicable) before injecting Bupivacaine Hydrochloride Injection, both the initial dose and all subsequent doses, to avoid intravascular or intrathecal injection. However, a negative aspiration for blood or cerebrospinal fluid does not ensure against an intravascular or intrathecal injection.
^Spl Unclassified Section
METHYLPREDNISOLONE ACETATE injection, suspension
NOT FOR USE IN NEONATES
CONTAINS BENZYL ALCOHOL
NOT FOR INTRAVENOUS USE
^ Chondrolysis With Intra-articular Infusion
Intra-articular infusions of local anesthetics including Bupivacaine Hydrochloride Injection following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are associated with chondrolysis. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2 ndmonth after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.
^ Risk Of Cardiac Arrest With Intravenous Regional Anesthesia Use (bier Block)
There have been reports of cardiac arrest and death during the use of bupivacaine for intravenous regional anesthesia (Bier Block). Information on safe dosages and techniques of administration of Bupivacaine Hydrochloride Injection in this procedure is lacking. Therefore, Bupivacaine Hydrochloride Injection is contraindicated for use with this technique [see Contraindications (4)] .
^General
When multidose vials are used, special care to prevent contamination of the contents is essential. A povidone-iodine solution or similar product is recommended to cleanse the vial top prior to aspiration of contents. (See WARNINGS .) This product, like many other steroid formulations, is sensitive to heat. Therefore, it should not be autoclaved when it is desirable to sterilize the outside of the vial.
The lowest possible dose of corticosteroid should be used to control the condition under treatment. When reduction in dosage is possible, the reduction should be gradual.
Since complications of treatment with glucocorticoids are dependent on the size of the dose and duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.
Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.
Cardio-renal Caution is required in patients with systemic sclerosis because an increased incidence of scleroderma renal crisis has been observed with corticosteroids, including methylprednisolone.
As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.
Endocrine Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted.
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.
Gastrointestinal Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis, since they may increase the risk of a perforation.
Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent.
There is an enhanced effect due to decreased metabolism of corticosteroids in patients with cirrhosis.
Parenteral Administration Intra-articular injected corticosteroids may be systemically absorbed.
Appropriate examination of any joint fluid is necessary to exclude a septic process.
A marked increase in pain associated by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.
Injection of a steroid into an infected site is to be avoided. Local injection of a steroid into a previously infected joint is not usually recommended.
Musculoskeletal Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (e.g., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy.
Neuro-psychiatric An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
Ophthalmic Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.
Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation.
Tumor Lysis Syndrome
In post marketing experience, tumor lysis syndrome (TLS) has been reported in patients with malignancies, including hematological malignancies and solid tumors, following the use of systemic corticosteroids alone or in combination with other chemotherapeutic agents. Patients at high risk of TLS, such as patients with tumors that have a high proliferative rate, high tumor burden and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precautions should be taken.
^Geriatric Use
Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
^ Risk Of Use In Patients With Impaired Cardiovascular Function
Bupivacaine Hydrochloride Injection should be given in reduced doses in patients with impaired cardiovascular function (e.g., hypotension, heartblock) because they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by Bupivacaine Hydrochloride Injection. Monitor patients closely for blood pressure, heart rate, and ECG changes.
^ Pharmacodynamics
Systemic absorption of bupivacaine produces effects on the cardiovascular system and 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. These cardiovascular changes are more likely to occur after unintended intravascular injection of bupivacaine [see Warnings and Precautions (5.9)] .
Following systemic absorption, bupivacaine can produce CNS stimulation, CNS depression, or both. Apparent central stimulation is manifested as restlessness, tremors, and shivering, progressing to convulsions, followed by CNS depression and coma progressing ultimately to respiratory arrest. However, bupivacaine has a primary depressant effect on the medulla and on higher centers. The depressed stage may occur without a prior excited state.
The duration of local anesthesia after administration of Bupivacaine Hydrochloride Injection is longer than that observed after administration of other commonly used short-acting local anesthetics. There appears to be a period of analgesia that persists after the resolution of the block and return of sensation.
The onset of action following dental injections is usually 2 to 10 minutes and may last up to 7 hours.
^Description
Methylprednisolone acetate injectable suspension, USP is a sterile anti-inflammatory glucocorticoid for intramuscular, intra-articular, soft tissue, or intralesional injection. It is available in 40 mg/mL strength:
Each mL of these preparations contains:
Methylprednisolone acetate..................................40 mg
Polyethylene glycol 3350...................................29.1 mg
Polysorbate 80................................................ 1.94 mg
Monobasic sodium phosphate monohydrate........ 6.8 mg
Dibasic sodium phosphate anhydrous USP............1.42 mg
Benzyl alcohol added as a preservative............... 9.16 mg
Sodium Chloride was added to adjust tonicity.
When necessary, pH was adjusted with sodium hydroxide and/or hydrochloric acid.
The pH of the finished product remains within the USP specified range (e.g., 3.5 to 7.0).
The chemical name for methylprednisolone acetate is pregna-1,4-diene-3,20- dione, 21-(acetyloxy)-11,17-dihydroxy-6-methyl-,(6α,11β) and 11β,17,21-Trihydroxy-6α-methylpregna-1,4-diene-3,20-dione 21-acetate the molecular weight is 416.51. The structural formula is represented below:
Methylprednisolone acetate sterile aqueous suspension contains methylprednisolone acetate which is the 6-methyl derivative of prednisolone. Methylprednisolone acetate is a white or practically white, odorless, crystalline powder which melts at about 215° with some decomposition. It is soluble in dioxane, sparingly soluble in acetone, alcohol, chloroform, and methanol, and slightly soluble in ether. It is practically insoluble in water.
^Uses
^ Use In Epidural Anesthesia
During epidural administration, administer Bupivacaine Hydrochloride Injection, 0.5% (5 mg/mL) and 0.75% (7.5 mg/mL) solutions in incremental doses of 3 mL to 5 mL with sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection. Administer injections slowly, with frequent aspirations before and during the injection to avoid intravascular injection. Perform syringe aspirations before and during each supplemental injection in continuous (intermittent) catheter techniques. In obstetrics, use ONLY the 0.5% (5 mg/mL) and 0.25% (2.5 mg/mL) concentrations of Bupivacaine Hydrochloride Injection [see Warnings and Precautions (5.1)]; incremental doses of 3 mL to 5 mL of the 0.5% (5 mg/mL) 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 clinically contraindicated. Use only the single-dose vials for caudal or epidural anesthesia; avoid use of the multiple-dose vials for these procedures, which contain a preservative [see Dosage and Administration (2.1 ), Warnings and Precautions ( 5.9)] .
^Directions
^How Supplied
Methylprednisolone Acetate Injectable Suspension, USP is available as white to off white aqueous sterile suspension. The drug product is presented in 5 mL clear USP tubular Type I glass vials stoppered with 13 mm chloro butyl rubber stoppers and sealed with 13 mm flip-off seal. Methylprednisolone Acetate Injectable Suspension, USP is supplied in the following strengths and package sizes:
40 mg per mL
5 mL Multiple-dose Vial NDC 0781-3522-75
Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Distributed by Sandoz Inc. Princeton, NJ 08540
Revised January 2024
^ Risk Of Adverse Reactions With Use In Head And Neck Area
Small doses of local anesthetics (e.g., Bupivacaine Hydrochloride Injection) injected into the head and neck area, including retrobulbar, dental, and stellate ganglion blocks, may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. The injection procedures require the utmost care. Confusion, convulsions, respiratory depression, and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde flow to the cerebral circulation. They may also be due to puncture of the dural sheath of the optic nerve during retrobulbar block with diffusion of any local anesthetic along the subdural space to the midbrain. Monitor circulation and respiration and constantly observe patients receiving Bupivacaine Hydrochloride Injection blocks. Resuscitative equipment and drugs, and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded [see Dosage and Administration (2.2)].
^ Use In Ophthalmic Surgery
When Bupivacaine Hydrochloride Injection 0.75% (7.5 mg/mL) 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 [see Warnings and Precautions (5.15)] .
^Contraindications
Methylprednisolone acetate injectable suspension is contraindicated in patients with known hypersensitivity to the product and its constituents.
Intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura.
Methylprednisolone acetate Sterile Aqueous Suspension is contraindicated for intrathecal administration. Reports of severe medical events have been associated with this route of administration.
Methylprednisolone acetate injectable suspension is contraindicated for use in premature infants because the formulation contains benzyl alcohol. (See WARNINGS and PRECAUTIONS: Pediatric Use .)
Methylprednisolone acetate injectable suspension is contraindicated in systemic fungal infections, except when administered as an intra-articular injection for localized joint conditions (see WARNINGS: Infections, Fungal Infections ).
^ Drugs Associated With Methemoglobinemia
Patients who are administered Bupivacaine Hydrochloride Injection are at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics [see Warnings and Precautions (5.3)] .
^Do Not Use
^3 Dosage Forms And Strengths
Bupivacaine Hydrochloride Injection, USP is a clear, colorless solution available as:
^Clinical Pharmacology
Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids.
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt retaining properties, are used in replacement therapy in adrenocortical deficiency states. Their synthetic analogs are used primarily for their anti- inflammatory effects in disorders of many organ systems.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body’s immune response to diverse stimuli.
^ Pediatric Use
Bupivacaine Hydrochloride Injection is approved for use in adults. Administration of Bupivacaine Hydrochloride Injection in pediatric patients younger than 12 years is not recommended.
Continuous infusions of bupivacaine in pediatric patients have been reported to result in high systemic levels of bupivacaine and seizures; high plasma levels may also be associated with cardiovascular abnormalities.
^Stop Use And Ask A Doctor If
^Dosage & Administration
NOTE: CONTAINS BENZYL ALCOHOL (see WARNINGSand PRECAUTIONS: Pediatric Use)
Because of possible physical incompatibilities, Methylprednisolone acetate Sterile Aqueous Suspension should not be diluted or mixed with other solutions.
The initial dosage of parenterally administered Methylprednisolone acetate injectable suspension will vary from 4 to 120 mg, depending on the specific disease entity being treated. However, in certain overwhelming, acute, life-threatening situations, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages.
It Should Be Emphasized that Dosage Requirements Are Variable and Must Be Individualized on the Basis of the Disease Under Treatment and the Response of the Patient.After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation, it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient’s condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
A. Administration for Local Effect Therapy with Methylprednisolone acetate injectable suspension does not obviate the need for the conventional measures usually employed. Although this method of treatment will ameliorate symptoms, it is in no sense a cure and the hormone has no effect on the cause of the inflammation. 1. Rheumatoid Arthritis and Osteoarthritis. The dose for intra-articular administration depends upon the size of the joint and varies with the severity of the condition in the individual patient. In chronic cases, injections may be repeated at intervals ranging from one to five or more weeks, depending upon the degree of relief obtained from the initial injection. The doses in the following table are given as a general guide:
Procedure:It is recommended that the anatomy of the joint involved be reviewed before attempting intra-articular injection. In order to obtain the full anti- inflammatory effect, it is important that the injection be made into the synovial space. Employing the same sterile technique as for a lumbar puncture, a sterile 20 to 24 gauge needle (on a dry syringe) is quickly inserted into the synovial cavity. Procaine infiltration is elective. The aspiration of only a few drops of joint fluid proves the joint space has been entered by the needle. The injection site for each joint is determined by that location where the synovial cavity is most superficial and most free of large vessels and nerves. With the needle in place, the aspirating syringe is removed and replaced by a second syringe containing the desired amount of Methylprednisolone acetate injectable suspension. The plunger is then pulled outward slightly to aspirate synovial fluid and to make sure the needle is still in the synovial space. After injection, the joint is moved gently a few times to aid mixing of the synovial fluid and the suspension. The site is covered with a small sterile dressing.
Suitable sites for intra-articular injection are the knee, ankle, wrist, elbow, shoulder, phalangeal, and hip joints. Since difficulty is not infrequently encountered in entering the hip joint, precautions should be taken to avoid any large blood vessels in the area. Joints not suitable for injection are those that are anatomically inaccessible such as the spinal joints and those like the sacroiliac joints that are devoid of synovial space. Treatment failures are most frequently the result of failure to enter the joint space. Little or no benefit follows injection into surrounding tissue. If failures occur when injections into the synovial spaces are certain, as determined by aspiration of fluid, repeated injections are usually futile. If a local anesthetic is used prior to injection of Methylprednisolone acetate injectable suspension, the anesthetic package insert should be read carefully and all the precautions observed. 2. Bursitis.The area around the injection site is prepared in a sterile way and a wheal at the site made with 1 percent procaine hydrochloride solution. A 20 to 24 gauge needle attached to a dry syringe is inserted into the bursa and the fluid aspirated. The needle is left in place and the aspirating syringe changed for a small syringe containing the desired dose. After injection, the needle is withdrawn and a small dressing applied. 3. Miscellaneous: Ganglion, Tendinitis, Epicondylitis.In the treatment of conditions such as tendinitis or tenosynovitis, care should be taken following application of a suitable antiseptic to the overlying skin to inject the suspension into the tendon sheath rather than into the substance of the tendon. The tendon may be readily palpated when placed on a stretch. When treating conditions such as epicondylitis, the area of greatest tenderness should be outlined carefully and the suspension infiltrated into the area. For ganglia of the tendon sheaths, the suspension is injected directly into the cyst. In many cases, a single injection causes a marked decrease in the size of the cystic tumor and may effect disappearance. The usual sterile precautions should be observed, of course, with each injection. The dose in the treatment of the various conditions of the tendinous or bursal structures listed above varies with the condition being treated and ranges from 4 to 30 mg. In recurrent or chronic conditions, repeated injections may be necessary. 4. Injections for Local Effect in Dermatologic Conditions.Following cleansing with an appropriate antiseptic such as 70% alcohol, 20 to 60 mg is injected into the lesion. It may be necessary to distribute doses ranging from 20 to 40 mg by repeated local injections in the case of large lesions. Care should be taken to avoid injection of sufficient material to cause blanching since this may be followed by a small slough. One to four injections are usually employed, the intervals between injections varying with the type of lesion being treated and the duration of improvement produced by the initial injection.
When multidose vials are used, special care to prevent contamination of the contents is essential. (See WARNINGS.) B. Administration for Systemic Effect The intramuscular dosage will vary with the condition being treated. When employed as a temporary substitute for oral therapy, a single injection during each 24-hour period of a dose of the suspension equal to the total daily oral dose of MEDROL® Tablets (methylprednisolone tablets, USP) is usually sufficient. When a prolonged effect is desired, the weekly dose may be calculated by multiplying the daily oral dose by 7 and given as a single intramuscular injection. In pediatric patients, the initial dose of methylprednisolone may vary depending upon the specific disease entity being treated. The range of initial doses is 0.11 to 1.6 mg/kg/day. Dosage must be individualized according to the severity of the disease and response of the patient. In patients with the adrenogenital syndrome, a single intramuscular injection of 40 mg every two weeks may be adequate. For maintenance of patients with rheumatoid arthritis, the weekly intramuscular dose will vary from 40 to 120 mg. The usual dosage for patients with dermatologic lesionsbenefited by systemic corticoid therapy is 40 to 120 mg of methylprednisolone acetate administered intramuscularly at weekly intervals for one to four weeks. In acute severe dermatitis due to poison ivy, relief may result within 8 to 12 hours following intramuscular administration of a single dose of 80 to 120 mg. In chronic contact dermatitis, repeated injections at 5 to 10 day intervals may be necessary. In seborrheic dermatitis, a weekly dose of 80 mg may be adequate to control the condition. Following intramuscular administration of 80 to 120 mg to asthmatic patients, relief may result within 6 to 48 hours and persist for several days to two weeks. If signs of stress are associated with the condition being treated, the dosage of the suspension should be increased. If a rapid hormonal effect of maximum intensity is required, the intravenous administration of highly soluble methylprednisolone sodium succinate is indicated. For the purpose of comparison, the following is the equivalent milligram dose of the various glucocorticoids:
These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.
^ Geriatric Use
Patients 65 years and over, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing anesthesia with Bupivacaine Hydrochloride Injection.
In clinical studies of bupivacaine, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger adult patients.
Differences in various pharmacokinetic parameters have been observed between elderly and younger adult patients [see Clinical Pharmacology (12.3)].
This product is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Elderly patients may require lower doses of Bupivacaine Hydrochloride Injection.
^ Methemoglobinemia
Cases of methemoglobinemia have been reported in association with local anesthetic use. Although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition [see Drug Interactions (7.5)] . If local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended.
Signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious CNS and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. Discontinue Bupivacaine Hydrochloride Injection and any other oxidizing agents. Depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. A more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
^ Dose-related Toxicity
The safety and effectiveness of Bupivacaine Hydrochloride Injection depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be performed after injection of Bupivacaine Hydrochloride Injection solutions.
Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death.
During major regional nerve blocks, such as those of the brachial plexus or lower extremity, the patient should have an indwelling intravenous catheter to assure adequate intravenous access. Use the lowest dosage of Bupivacaine Hydrochloride Injection that results in effective anesthesia to avoid high plasma levels and serious adverse effects. Avoid rapid injection of a large volume of Bupivacaine Hydrochloride Injection solution and administer fractional (incremental) doses when feasible.
Injection of repeated doses of Bupivacaine Hydrochloride Injection may cause significant increases in plasma levels with each repeated dose due to slow accumulation of the drug or its metabolites, or to slow metabolic degradation. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical status.
^ Renal Impairment
Bupivacaine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with renal impairment. This should be considered when selecting the Bupivacaine Hydrochloride Injection dosage [see Use in Specific Populations (8.5)] .
^Carcinogenesis, Mutagenesis, Impairment Of Fertility
No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis or mutagenesis.
Steroids may increase or decrease motility and number of spermatozoa in some patients.
Corticosteroids have been shown to impair fertility in male rats.
^Information For The Patient
Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision, to advise any medical attendants that they are taking corticosteroids, and to seek medical advice at once should they develop fever or other signs of infection.
Persons who are on corticosteroids should be warned to avoid exposure to chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.
^Purpose
Antiseptic
^ Important Dosage And Administration Information
^ Local Anesthetics
The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with Bupivacaine Hydrochloride Injection cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Dosage and Administration (2.1), Warnings and Precautions (5.2)] .
^6 Adverse Reactions
The following clinically significant adverse reactions have been reported and described in the Warnings and Precautions section of the labeling:
The following adverse reactions from voluntary reports or clinical studies have been reported with bupivacaine. Because many of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Adverse reactions to Bupivacaine Hydrochloride Injection 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 reactions that demand immediate counter-measures were related to the CNS and the cardiovascular system. These adverse reactions were generally dose-related and due to high plasma levels which may have resulted 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 intrathecal 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) has resulted 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 have occurred. This has led to secondary cardiac arrest when untreated.
^Nursing Mothers
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to continue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
^Pregnancy
Teratogenic Effects Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.
This product contains benzyl alcohol as a preservative. Benzyl alcohol can cross the placenta. See PRECAUTIONS: Pediatric use .
^ Risk Of Cardiac Arrest With Use Of Bupivacaine Hydrochloride Injection In Obstetrical Anesthesia
There have been reports of cardiac arrest with difficult resuscitation or death during use of Bupivacaine Hydrochloride Injection for epidural anesthesia in obstetrical patients. In most cases, this has followed use of the 0.75% (7.5 mg/mL) concentration. Resuscitation has been difficult or impossible despite apparently adequate preparation and appropriate management. Cardiac arrest has occurred after convulsions resulting from systemic toxicity, presumably following unintentional intravascular injection. The 0.75% (7.5 mg/mL) concentration of Bupivacaine Hydrochloride Injection is not recommended for obstetrical anesthesia and should be reserved for surgical procedures where a high degree of muscle relaxation and prolonged effect are necessary.
^ Pharmacokinetics
Systemic plasma levels of bupivacaine following administration of Bupivacaine Hydrochloride Injection do not correlate with local efficacy.
^1 Indications And Usage
Bupivacaine Hydrochloride Injection is indicated in adults for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures. Specific concentrations and presentations of Bupivacaine Hydrochloride Injection are recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see Dosage and Administration (2.2)].
^ Mechanism Of Action
Bupivacaine blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.
^Warnings
For external use only.