Bupivacaine and Epinephrine

MARCAINE / MARCAINE WITH EPINEPHRINE 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 MARCAINE / MARCAINE WITH EPINEPHRINE are recommended for each type of block indicated to produce local or regional anesthesia or analgesia. MARCAINE contains bupivacaine, an amide local anesthetic, and MARCAINE WITH EPINEPHRINE is a combination of bupivacaine, an amide local anesthetic, and epinephrine, an alpha and beta-adrenergic agonist. For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended.

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: pain, temperature, touch, proprioception, and skeletal muscle tone. Epinephrine is a vasoconstrictor added to bupivacaine to slow absorption into the general circulation and thus prolong maintenance of an active tissue concentration.

• Not for intrathecal use. • Avoid use of solutions containing antimicrobial preservatives (i.e., multiple-dose vials) for epidural or caudal anesthesia. • Three mL of MARCAINE WITH EPINEPHRINE without antimicrobial preservative (0.5% bupivacaine with 1:200,000 epinephrine ) is recommended for use as a test dose prior to caudal and lumbar epidural blocks when clinical conditions permit. • See full prescribing information for: - Recommended concentrations and dosages of MARCAINE / MARCAINE WITH EPINEPHRINE according to type of block. - Additional dosage and administration information pertaining to use in epidural anesthesia, test dose for caudal and lumbar epidural blocks, use in dentistry, and use in ophthalmic surgery.

MARCAINE / MARCAINE WITH EPINEPHRINE is contraindicated in: • obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death. • intravenous regional anesthesia (Bier Block). • patients with a known hypersensitivity to bupivacaine or to any local anesthetic agent of the amide-type or to other components of MARCAINE / MARCAINE WITH EPINEPHRINE. • Obstetrical paracervical block anesthesia. Its use in this technique has resulted in fetal bradycardia and death. • Intravenous regional anesthesia (Bier Block).

Boxed warning (risk of cardiac arrest with use of marcaine in obstetrical anesthesia): There have been reports of cardiac arrest with difficult resuscitation or death during use of MARCAINE 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. • Dose-Related Toxicity: Monitor cardiovascular and respiratory vital signs and patient's state of consciousness after injection of MARCAINE / MARCAINE WITH EPINEPHRINE. • Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetic use. See full prescribing information for more detail on managing these risks.

The following clinically significant adverse reactions have been reported and described in the Warnings and Precautions section of the labeling: • Cardiac Arrest in Obstetrical Anesthesia • Dose-Related Toxicity • Methemoglobinemia • Chondrolysis with Intra-Articular Infusion • Severe, Persistent Hypertension, Cerebrovascular Accidents, and Bradycardia Due to Drug Interactions • Cardiac Arrest with Intravenous Regional Anesthesia Use • Allergic-Type Reactions • Systemic Toxicities with Unintended Intravascular or Intrathecal Injection • Respiratory Arrest Following Retrobulbar Block The following adverse reactions from voluntary reports or clinical studies have been reported with bupivacaine or bupivacaine and epinephrine.

• Local Anesthetics: The toxic effects of local anesthetics are additive. Monitor for neurologic and cardiovascular effects when additional local anesthetics are administered. • Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: Administration of MARCAINE WITH EPINEPHRINE to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. • Ergot-Type Oxytocic Drugs: Concurrent administration of MARCAINE WITH EPINEPHRINE and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. • Nonselective Beta-Adrenergic Antagonists: Administration of MARCAINE WITH EPINEPHRINE (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).