Marcaine

Tell your doctor if you have ever had an allergic reaction to any type of numbing medicine.

Before receiving this medication, tell your doctor if you have kidney or liver disease, anemia (lack of red blood cells), a bleeding or blood clotting disorder, syphilis, polio, a brain or spinal cord tumor, numbness or tingling, chronic back pain, headache caused by surgery, low or high blood pressure, a curved spine, or arthritis.

You will be watched closely after receiving bupivacaine, to make sure you do not have a reaction to the medication.

This medication can cause numbness over a large portion of your body. Take care to avoid injury before the feeling has returned completely. After a dental procedure, avoid eating, chewing gum, or drinking a hot beverage until your mouth is no longer numb.

Some epidural numbing medications can have long-lasting or permanent effects on certain body processes such as sexual function, bowel or bladder control, and movement or feeling in your legs or feet. Talk with your doctor about your specific risk of nerve damage from bupivacaine.

This medication can cause numbness over a large portion of your body. Take care to avoid injury before the feeling has returned completely.

After a dental procedure, avoid eating, chewing gum, or drinking a hot beverage until your mouth is no longer numb.

Serious side effects have been reported with Marcaine including the following:

• Allergic-type reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of allergic-type reactions.
  • Itching, hives, and redness
  • Swelling of the throat or face
  • Increased heart rate
  • Sneezing
  • Nausea
  • Vomiting
  • Dizziness
  • Loss of consciousness
  • Excessive sweating
  • Elevated temperature or fever
• Neurologic reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of neurologic reactions.
  • Decreased heart rate
  • Urinary retention
  • Fecal and urinary incontinence
  • Persistent anesthesia
  • Tingling in the extremities
  • Weakness
  • Paralysis of the lower extremities
  • Headache
  • Backache
  • Septic meningitis (inflammation of the brain and spinal cord)

Marcaine can cause drowsiness, dizziness, and blurred vision. Do not drive or operate heavy machinery until you know how Marcaine affects you.

Do not take Marcaine if you:

• are allergic to Marcaine or to any of its ingredients

Marcaine injection should not be used in obstetrical paracervical block (local anesthetic injection around cervix) anesthesia.

Before taking Marcaine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Marcaine or to any of its ingredients
• have or have had liver problems
• have or have had heart problems
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Use Marcaine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot.
• Your doctor will give this medicine.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If you need to store Marcaine at home, talk with your doctor, nurse, or pharmacist about how to store it.

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:

Epinephrine is (-)-3,4-Dihydroxy-α-[(methylamino)methyl] benzyl alcohol. It has the following structural formula:

Marcaine is available in sterile isotonic solutions with and without epinephrine (as bitartrate) 1:200,000 for injection via local infiltration, peripheral nerve block, and caudal and lumbar epidural blocks. Solutions of Marcaine may be autoclaved if they do not contain epinephrine. Solutions are 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.

MarcaineSterile isotonic solutions containing sodium chloride. In multiple-dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 4 and 6.5 with sodium hydroxide or hydrochloric acid.

Marcaine with epinephrine 1:200,000 (as bitartrate)Sterile isotonic solutions containing sodium chloride. Each mL contains bupivacaine hydrochloride and 0.0091 mg epinephrine bitartrate, with 0.5 mg sodium metabisulfite, 0.001 mL monothioglycerol, and 2 mg ascorbic acid as antioxidants, 0.0017 mL 60% sodium lactate buffer, and 0.1 mg edetate calcium disodium as stabilizer. In multiple-dose vials, each mL also contains 1 mg methylparaben as antiseptic preservative. The pH of these solutions is adjusted to between 3.4 and 4.5 with sodium hydroxide or hydrochloric acid. The specific gravity of Marcaine 0.5% with epinephrine 1:200,000 (as bitartrate) at 25°C is 1.008 and at 37°C is 1.008.

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.

Local anesthetic solutions containing antimicrobial preservatives, i.e., those supplied in multiple-dose vials, should not be used for epidural or caudal anesthesia because safety has not been established with regard to intrathecal injection, either intentionally or unintentionally, of such preservatives.

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.

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.

Marcaine with epinephrine 1:200,000 or other vasopressors should not be used concomitantly with ergot-type oxytocic drugs, because a severe persistent hypertension may occur. Likewise, solutions of Marcaine containing a vasoconstrictor, such as epinephrine, should be used with extreme caution in patients receiving monoamineoxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe prolonged hypertension may result.

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

Mixing or the prior or intercurrent use of any other local anesthetic with Marcaine 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 Marcaine for intravenous regional anesthesia (Bier Block). Information on safe dosages and techniques of administration of Marcaine in this procedure is lacking. Therefore, Marcaine is not recommended for use in this technique.

Marcaine with epinephrine 1:200,000 contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Single-dose ampuls and single-dose vials of Marcaine without epinephrine do not contain sodium metabisulfite.

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 LD50 in mice is 6 mg/kg to 8 mg/kg and 38 mg/kg to 54 mg/kg respectively.

These solutions are not for spinal anesthesia.

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

Marcaine―Solutions of Marcaine that do not contain epinephrine may be autoclaved. Autoclave at 15-pound pressure, 121°C (250°F) for 15 minutes.

Marcaine with epinephrine 1:200,000 (as bitartrate)―Solutions of Marcaine that contain epinephrine should not be autoclaved and should be protected from light. Do not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate.

Revised: 10/2014

                                                                               EN-3536

Hospira, Inc., Lake Forest, IL 60045 USA                                                                              

50 mL Multiple-Dose Vial

Marcaine™ 0.25%
bupivacaine HCl injection, USP
125 mg/50 mL
(2.5 mg/mL)

Each mL contains 2.5 mg bupivacaine
HCl, with 1 mg methylparaben as
antiseptic preservative and NaCl to make
isotonic, in Water for Injection.
pH adjusted with NaOH or HCl.

for INFILTRATION and NERVE BLOCK