LIDOCAINE ANHYDROUS Drug Interactions: What You Need to Know

INTERACTIONS

• Local Anesthetics: The toxic effects of local anesthetics are additive. Monitor for neurologic and cardiovascular effects when additional local anesthetics are administered ( 7.1 )
• Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: Administration of lidocaine hydrochloride to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension Concurrent use of these agents should generally be avoided ( 5.5 , 7.2 )
• Ergot-type Oxytocic drugs: Concurrent administration of lidocaine hydrochloride and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents ( 5.5 , 7.3 )
• Nonselective Beta-Adrenergic Antagonists: Administration of lidocaine hydrochloride in patients receiving nonselective beta-adrenergic antagonist may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. ( 5.5 , 7.4 )
• Drugs Associated with Methemoglobinemia: Patients are at increased risk of developing methemoglobinemia when concurrently exposed to nitrates, nitrites, local anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants and other drugs ( 7.5 ).
• Potent Inhalation Anesthetics: Serious dose-related cardiac arrhythmias may occur if preparations containing epinephrine are used in patients during or following the administration of potent inhalation anesthetics (5.11, 7.6)
• Geriatric Use: Elderly patients should be given reduced doses commensurate with their age and physical condition ( 8.5 )
• Hepatic Impairment: consider reduced dosing and increased monitoring for local anesthetic systemic toxicity in patients with hepatic impairment ( 8.6 )

7.1 Local Anesthetics The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with lidocaine hydrochloride cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>.

7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants The administration of lidocaine hydrochloride to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situation when concurrent therapy is necessary, careful monitoring of the patient’s hemodynamic status is essential <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 )]</span>.

7.3 Ergot-Type Oxytocic Drugs Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Avoid use of lidocaine hydrochloride concomitantly with ergot-type oxytocic drugs <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 )]</span>.

7.4 Nonselective Beta-Adrenergic Antagonists Administration of lidocaine hydrochloride in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient&apos;s blood pressure and heart rate is essential <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.5 )]</span>.

7.5 Drugs Associated with Methemoglobinemia Patients that are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following oxidizing agents: Class Examples Nitrates/Nitrites nitroglycerin, nitroprusside, nitric oxide, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, rasburicase, ifosfamide, hydroxyurea Antibiotics dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid Antimalarials chloroquine, primaquine Anticonvulsants phenytoin, sodium valproate, phenobarbital Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

Lidocaine hydrochloride injection is contraindicated in patients with a known hypersensitivity to lidocaine or to any local anesthetics of the amide type or to other components of lidocaine hydrochloride injection.

• Known hypersensitivity to any local anesthetic agent of the amide-type or to other components of lidocaine hydrochloride injection.

AND PRECAUTIONS

• Dose-Related Toxicity: Monitor cardiovascular and respiratory vital signs and patient’s state of consciousness after injection of lidocaine hydrochloride injection. ( 5.1 )
• Methemoglobinemia: Cases of methemoglobinemia have been reported in association with local anesthetics use. See full prescribing information for more details on managing these risks. ( 5.2 )
• Chondrolysis with Intra-Articular Infusion: Avoid Intra-articular infusions as there have been post-marketing reports of chondrolysis in patients receiving such infusion. ( 5.4 )
• Allergic-Type Reactions to Sulfites in Lidocaine Hydrochloride and Anaphylactic Reactions: Lidocaine hydrochloride injection without epinephrine does not contain sodium metabisulfite. ( 5.6 )
• 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 injection. ( 5.7 )

5.1 Dose Related Toxicity The safety and effectiveness of lidocaine hydrochloride 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&apos;s state of consciousness should be performed after injection of lidocaine hydrochloride solution. 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 that results in effective anesthesia to avoid high plasma levels and serious adverse effects. Avoid rapid injection of a large volume of lidocaine hydrochloride solution and administer fractional (incremental) doses when feasible. Injection of repeated doses of lidocaine hydrochloride 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 <span class="opacity-50 text-xs">[see Drug Interactions ( 7.5 )]</span> . 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 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.

5.4 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. 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 nd 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.

5.5 Risk of Adverse Reactions Due to Drug Interactions with Lidocaine Hydrochloride Injection Risk of Severe, Persistent Hypertension Due to Drug Interactions Between Lidocaine Hydrochloride and Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Administration of lidocaine hydrochloride in patients receiving monoamine oxidase inhibitors (MAOI), or tricyclic antidepressants may result in severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient&apos;s hemodynamic status is essential <span class="opacity-50 text-xs">[see Drug Interactions ( 7.2 )]</span>. Risk of Severe, Persistent Hypertension or Cerebrovascular Accidents Due to Drug Interactions Between lidocaine hydrochloride and Ergot-Type Oxytocic Drugs Concurrent administration of lidocaine hydrochloride and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Avoid use of lidocaine hydrochloride concomitantly with ergot-type oxytocic drugs <span class="opacity-50 text-xs">[see Drug Interactions ( 7.3 )]</span>. Risk of Hypertension and Bradycardia Due to Drug Interactions Between Lidocaine Hydrochloride and Nonselective Beta-Adrenergic Antagonists Administration of lidocaine hydrochloride in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient&apos;s blood pressure and heart rate is essential <span class="opacity-50 text-xs">[see Drug Interactions ( 7.4 )]</span>

5.6 Allergic-Type Reactions to Sulfites in Lidocaine Hydrochloride Injection-MPF and Anaphylactic Reactions Lidocaine hydrochloride injection without epinephrine does not contain sodium metabisulfite. Anaphylactic reactions may occur following administration of lidocaine hydrochloride <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span> . Lidocaine hydrochloride should be used with caution in persons with known drug sensitivities. Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine hydrochloride.

5.7 Risk of Systemic Toxicities with Unintended Intravascular or Intrathecal Injection Unintended intravascular or intrathecal injection of lidocaine hydrochloride 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 (&quot;Total or High Spinal&quot;). A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia <span class="opacity-50 text-xs">[see Adverse Reactions ( 6 )]</span>. Aspirate for blood or cerebrospinal fluid (where applicable) before injecting lidocaine hydrochloride, 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. Use of Test Dose with Epidural Anesthesia To serve as a warning of unintended intravascular or intrathecal injection, 3 mL of lidocaine hydrochloride with epinephrine without antimicrobial preservative (1.5% lidocaine with 1:200,000 epinephrine) may be used as a test dose prior to administration of the full dose in caudal and lumbar epidural blocks <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.4 )]</span> . Three mL of lidocaine hydrochloride with epinephrine (1.5% lidocaine with 1:200,000 epinephrine) without antimicrobial preservative contains 45 mg lidocaine and 15 mcg epinephrine. An intravascular or intrathecal injection is still possible even if results of the test dose are negative. Signs/symptoms of unintended intravascular or intrathecal injection of the test dose of lidocaine hydrochloride with epinephrine and monitoring recommendations are described below.

• Unintended intravascular injection: Likely to produce a transient “epinephrine response” within 45 seconds, consisting of an increase in heart rate and/or systolic blood pressure, circumoral pallor, palpitations, and nervousness in the unsedated patient. The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds. Therefore, following the test dose, the heart rate should be monitored for increases. Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect a transient rise in systolic blood pressure.
• Unintended intrathecal injection: Evidenced within a few minutes by signs of spinal block (e.g., decreased sensation of the buttocks, paresis of the legs, or, in the sedated patient, absent knee jerk). The test dose itself may produce a systemic toxic reaction, high spinal or epinephrine-induced cardiovascular effects [see Overdosage ( 10 )].

5.8 Risk of Toxicity in Patients with Hepatic Impairment Because amide local anesthetics such as lidocaine are metabolized by the liver, consider reduced dosing and increased monitoring for lidocaine systemic toxicity in patients with moderate to severe hepatic impairment who are treated with lidocaine hydrochloride, especially with repeat doses <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.6 )]</span>.

5.9 Risk of Use in Patients with Impaired Cardiovascular Function Lidocaine hydrochloride injection should also be given in reduced doses in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs. Monitor patients closely for blood pressure, heart rate, and ECG changes.

5.12 Risk of Adverse Reactions with Use in the Head and Neck Area Small doses of local anesthetics (e.g., lidocaine hydrochloride) 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 lidocaine hydrochloride blocks. Resuscitative equipment and drugs, and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span>.

5.13 Familial Malignant Hyperthermia Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using).

5.14 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 lidocaine hydrochloride), 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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.14 )]</span> . 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.

5.16 Drug/Laboratory Test Interactions The intramuscular injection of lidocaine hydrochloride may result in an increase in creatine phosphokinase levels. Thus, the use of this enzyme determination, without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromised by the intramuscular injection of lidocaine hydrochloride.