Epinephrine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Dose-Related Toxicity : Monitor cardiovascular and respiratory vital signs and patient’s state of consciousness after injection of Lidocaine Hydrochloride and Epinephrine. • Methemoglobinemia : Cases of methemoglobinemia have been reported in association with local anesthetics use.

See full prescribing information for more details on managing these risks. • Chondrolysis with Intra-Articular Infusion : Avoid intra-articular infusions as there have been post-marketing reports of chondrolysis in patients receiving such infusion. • Allergic-Type Reactions to Sulfites in Lidocaine Hydrochloride and Epinephrine Injection and Anaphylactic Reactions : Lidocaine Hydrochloride and Epinephrine Injection 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. • Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection : Unintended intravascular or intrathecal injection may be associated with systemic toxicities, including CNS or cardiorespiratory depression and coma, progression ultimately to respiratory arrest.

Aspirate for blood or cerebrospinal fluid (where applicable) prior to each dose and consider using a test dose of Lidocaine Hydrochloride and Epinephrine.

5.1 Dose-Related Toxicity The safety and effectiveness of Lidocaine Hydrochloride and Epinephrine 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 Lidocaine Hydrochloride and Epinephrine 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 Lidocaine Hydrochloride and Epinephrine Injection that results in effective anesthesia to avoid high plasma levels and serious adverse effects.

Avoid rapid injection of a large volume of Lidocaine Hydrochloride and Epinephrine Injection solution and administer fractional (incremental) doses when feasible.

Injection of repeated doses of Lidocaine Hydrochloride and Epinephrine 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.

5.2 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 ].

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 abnormal coloration of the blood.

Methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death.

Discontinue Lidocaine Hydrochloride and Epinephrine Injection and any other oxidizing agents.

Depending on the severity of the symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration.

More severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

5.3 Antimicrobial Preservatives in Multiple-Dose Vials Avoid use of Lidocaine Hydrochloride and Epinephrine Injection solutions containing antimicrobial preservatives (i.e., those supplied in multiple-dose vials) for epidural or caudal anesthesia because safety has not been established with such use.

5.4 Chondrolysis with Intra-Articular Infusion 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.