alpha-Adrenergic Agonist

Lidocaine Hydrochloride and Epinephrine

Approved 21 Jun 1988InjectionInjectable

The FDA lists this product in 18 strengths and forms.

Indications

Lidocaine Hydrochloride and Epinephrine Injection is indicated in adult and pediatric patients 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 Lidocaine Hydrochloride and Epinephrine Injection are recommended for each type of block indicated to produce local or regional anesthesia or analgesia [see Dosage and Administration (2.2) ] .

Lidocaine Hydrochloride and Epinephrine Injection is a combination of lidocaine, an amide local anesthetic, and epinephrine, an alpha and beta adrenergic agonist. Lidocaine Hydrochloride and Epinephrine Injection is indicated in adult and pediatric patients 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.

For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended. ( 1 , 2.2 )

Contraindications

Lidocaine Hydrochloride and Epinephrine Injections are 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 and Epinephrine Injections. Known hypersensitivity to any local anesthetic agent of the amide-type or to other components of Lidocaine Hydrochloride and Epinephrine Injection. ( 4 )

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. ( 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 )

Indications

For each type of block indicated to produce local or regional anesthesia or analgesia, specific concentrations and presentations are recommended. ( 1 , 2.2 )

Contraindications

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. ( 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 )

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 and Epinephrine Injection 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 Epinephrine Injection 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 and Epinephrine Injection 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 )

7.1Local Anesthetics

The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with Lidocaine Hydrochloride and Epinephrine Injection cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity [see Warnings and Precautions (5.1) ] .

7.2Monoamine Oxidase Inhibitors and Tricyclic Antidepressants

The administration of Lidocaine Hydrochloride and Epinephrine Injection to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient’s hemodynamic status is essential [see Warnings and Precautions (5.5) ] .

7.3Ergot-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 and Epinephrine Injection concomitantly with ergot-type oxytocic drugs [see Warnings and Precautions (5.5) ] .

7.4Nonselective Beta-Adrenergic Antagonists Administration of Lidocaine Hydrochloride and Epinephrine Injection

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's blood pressure and heart rate is essential [see Warnings and Precautions (5.5) ] .

7.5Drugs 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

7.6Potent Inhalation Anesthetics

Serious dose-related cardiac arrhythmias may occur if preparations containing epinephrine (e.g., Lidocaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics [see Warnings and Precautions (5.11) ] .

7.7Phenothiazines and Butyrophenones Phenothiazines

and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of Lidocaine Hydrochloride with Epinephrine and these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Available published data and decades of clinical use with lidocaine hydrochloride in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Local anesthetics may cause varying degrees of toxicity to the mother and fetus and adverse reactions include alterations of the central nervous system, peripheral vascular tone and cardiac function (see Clinical Considerations ) .

In a published animal reproduction study, pregnant rats administered lidocaine by continuous subcutaneous infusion at a dose approximately 9.6 times the maximum recommended human dose (MRHD) of 500 mg in lidocaine hydrochloride during the period of organogenesis resulted in lower fetal body weights [ see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the United States general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Maternal adverse reactions Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves.

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. Elevating the patient’s legs will also help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously, and electronic fetal monitoring is highly advisable.

Labor or delivery Local anesthetics rapidly cross the placenta, and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity [see Clinical Pharmacology (12.3) ] . The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone and cardiac function.

However, dosage recommendations for spinal anesthesia are much lower than dosage recommendations for other major blocks. Spinal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Spinal anesthesia has also been reported to prolong the second stage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance.

The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. Data Animal Data Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by lidocaine hydrochloride. In a published study, lidocaine administered to pregnant rats by continuous subcutaneous infusion during the period of organogenesis at 100, 250, and 500 mg/kg/day, did not produce any structural abnormalities, but did result in lower fetal weights at 500 mg/kg/day dose (approximately 9.6 times the maximum recommended human dose [MRHD] of 500 mg lidocaine on a mg/m 2 basis) in the absence of maternal toxicity.

Adverse reactions

The following clinically significant adverse reactions have been reported and described in the Warnings and Precautions section of the labeling:

Dose-Related Toxicity [see Warnings and Precautions (5.1) ]
Methemoglobinemia [see Warnings and Precautions (5.2) ]
Chondrolysis with Intra-Articular Infusion [see Warnings and Precautions (5.4) ]
Severe, Persistent Hypertension, Cerebrovascular Accidents, and Bradycardia Due to Drug Interactions [see Warnings and Precautions (5.5) ]
Allergic-Type Reactions [see Warnings and Precautions (5.6) ]
Systemic Toxicities with Unintended Intravascular or Intrathecal Injection [see Warnings and Precautions (5.7) ]
Respiratory Arrest Following Retrobulbar Block [see Warnings and Precautions (5.14) ] The following adverse reactions from voluntary reports or clinical studies have been reported with lidocaine or lidocaine and epinephrine. 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 Lidocaine Hydrochloride are characteristic of those associated with other amide-type local anesthetic. 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, hypertension 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. When used for dental injections, paresthesia of the lips, tongue, and oral tissues have been reported. Persistent paresthesia lasting weeks to months and, in some instances, lasting greater than one year, have also been reported. Nervous System Disorders Adverse reactions were characterized by excitation and/or depression of the central nervous system and included lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The incidences of adverse reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration and the physical status of the patient. In a prospective review of 10,440 patients who received lidocaine hydrochloride for spinal anesthesia, the incidences of adverse reactions were reported to be about 3 percent each for positional headaches, hypotension and backache; 2 percent for shivering; and less than 1 percent each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with slow recovery (several months) or incomplete recovery have been reported in rare instances when caudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anesthetic procedures. There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration. In the practice of caudal or lumbar epidural block, unintentional penetration of the subarachnoid space by the catheter or needle has occurred. Subsequent adverse effects may have depended partially on the amount of drug administered intrathecally and the physiological and physical effects of a dural puncture. A high spinal has been characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia. Neurologic effects following epidural or caudal anesthesia have included spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities and loss of sphincter control, all of which had slow, incomplete, or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; and cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid. Neurologic effects following other procedures or routes of administration have included persistent anesthesia, paresthesia, weakness, paralysis, all with slow, incomplete, or no recovery. Convulsions : Incidence varied with the procedure used and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1% of local anesthetic administrations. The incidences of adverse neurologic reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient. Cardiac Disorders High doses or unintentional intravascular injection have led to high plasma levels and related depression of the myocardium, decreased cardiac output, heartblock, hypotension, bradycardia, ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, and cardiac arrest [see Warnings and Precautions (5.9) ]. Immune System Disorders Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Allergic reactions may occur as a result of sensitivity either to local anesthetic agents or to the methylparaben used as a preservative in the multiple-dose vials [see Warnings and Precautions (5.6) ] . There have been no reports of cross sensitivity between lidocaine hydrochloride and procainamide or between lidocaine hydrochloride and quinidine. Hematologic Methemoglobinemia [see Warnings and Precautions (5.2) ] . Most common adverse reactions are as follows:
Central Nervous System: Lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. ( 6 )
Cardiovascular System: Bradycardia, hypotension, and cardiovascular collapse. ( 6 )
Allergic: Cutaneous lesions, urticaria, edema or anaphylactoid reactions. ( 6 )
Neurologic: Positional headaches, hypotension and backache. ( 6 )
Hematologic: Methemoglobinemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc, at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Lidocaine Hydrochloride and Epinephrine

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Lidocaine Hydrochloride and Epinephrine

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Dose-Related Toxicity

5.2Methemoglobinemia Cases

5.3Antimicrobial Preservatives in Multiple-Dose Vials

5.4Chondrolysis with Intra-Articular Infusion

Interactions

7.1Local Anesthetics

7.2Monoamine Oxidase Inhibitors and Tricyclic Antidepressants

7.3Ergot-Type Oxytocic Drugs

7.4Nonselective Beta-Adrenergic Antagonists Administration of Lidocaine Hydrochloride and Epinephrine Injection

7.5Drugs Associated with Methemoglobinemia

7.6Potent Inhalation Anesthetics

7.7Phenothiazines and Butyrophenones Phenothiazines

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information

At a glance