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  • CLASSES

    Amide Local Anesthetics
    Anti-arrhythmics, Class I-B
    Compounding Kits Miscellaneous
    Ophthalmological Local Anaesthetics
    Other Agents for Local Oral Treatment
    Systemic Corticosteroids, Plain
    Topical Anti-hemorrhoidals
    Topical Local Anesthetics

    BOXED WARNING

    Children, infants, neonates, teething pain

    Lidocaine dosages in pediatric patients should be reduced, commensurate with age, body weight and physical condition. When multiple formulations of lidocaine are used at once, the amount systemically absorbed from all formulations must be considered. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated by pediatric patients, particularly by those who are debilitated or the acutely ill. Similar increases in systemic exposure are possible with repeat topical application. Certain products, such as lidocaine transdermal patches, have not been FDA-approved for application to pediatric patients. Non-prescription (OTC) products should not be used without healthcare professional advice in those under 2 years of age, or as directed on the product label. Do not use lidocaine viscous solution for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, cardiopulmonary arrest, severe brain injury, and death. The FDA reviewed 22 cases of serious adverse events that occurred in infants and young children between 5 months and 3.5 years of age after receiving lidocaine viscous solution for the treatment of mouth pain due to teething or stomatitis or who had accidental ingestions. Of the 22 cases, 6 cases resulted in death, 3 were categorized as life-threatening, 11 required hospitalization, and 2 required medical intervention without hospitalization. The FDA recommends against the use of topical pain relievers for teething pain due to the fact that they wash out of the mouth within minutes of application and can cause serious adverse reactions if they are swallowed in excessive amounts. Advise parents and caregivers with teething pain concerns to follow the American Academy of Pediatrics recommendations for the management of teething pain, which include using a teething ring chilled in the refrigerator (not frozen) and gently rubbing or massaging the gums with a finger. For other conditions, the use of viscous lidocaine in neonates, infants, and children 3 years of age and younger should be limited to those situations where safer alternatives are not available or have failed. To ensure safety, doses should be measured by an accurate device, administered no more often than every 3 hours, used only for the prescribed indication, and stored safely out of the reach of children immediately after use. When topical anesthetics are used in the mouth, the topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating.

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Amide local anesthetic and type IB antiarrhythmic; available as an ointment, jelly, patch, or aerosol for topical use, as an oral solution, as an ophthalmic gel, and as an injection for local anesthesia; used parenterally to treat acute, life-threatening ventricular arrhythmias.

    COMMON BRAND NAMES

    Akten, ANASTIA, AneCream, Anestacon, Aspercreme with Lidocaine, Astero, CidalEaze, EnovaRX, Glydo, LidaMantle, LIDO-K, Lidocare, Lidoderm, Lidomar, LidoRx, Lidosense 4, LMX 4, LMX 4 with Tegaderm, LMX 5, MENTHO-CAINE, Numbonex, Professional DNA Collection Kit, RectaSmoothe, RectiCare, Senatec, SOLUPAK, Tranzarel, VacuStim Silver, Xylocaine, Xylocaine MPF, Xylocaine Viscous, Zilactin-L, Zingo

    HOW SUPPLIED

    Akten Ophthalmic Gel: 3.5%
    ANASTIA/Lidocaine/Lidocaine Hydrochloride/LIDO-K/Numbonex/Senatec Topical Lotion: 2.75%, 3%
    AneCream/Aspercreme with Lidocaine/CidalEaze/LidaMantle/Lidocaine/Lidocaine Hydrochloride/Lidosense 4/LMX 4/LMX 4 with Tegaderm/LMX 5/RectaSmoothe/RectiCare Topical Cream: 3%, 4%, 5%
    Anestacon/Glydo/Lidocaine/Lidocaine Hydrochloride/Xylocaine Topical Jelly: 2%
    Astero/LidoRx/Tranzarel Topical Gel: 3%, 4%
    EnovaRX Topical Pwd F/Recon: 3g, 6g, 12g
    Lidocaine Hydrochloride, Dextrose/Lidocaine, Dextrose/Xylocaine Intrathecal Inj Sol: 5-7.5%
    Lidocaine/Lidocaine Hydrochloride Intravenous Sol: 1%
    Lidocaine/Lidocaine Hydrochloride/Lidocaine Hydrochloride, Dextrose/Lidocaine, Dextrose/Xylocaine/Xylocaine MPF Intravenous Inj Sol: 0.5%, 1%, 2%, 0.4-5%, 0.8-5%
    Lidocaine/Lidocaine Hydrochloride/Lidomar/Professional DNA Collection Kit/Xylocaine Viscous Oropharyngeal Sol: 2%
    Lidocaine/Lidocaine Hydrochloride/Lidomar/Professional DNA Collection Kit/Xylocaine Viscous Periodontal Sol: 2%
    Lidocaine/Lidocaine Hydrochloride/VacuStim Silver/Xylocaine/Zilactin-L Topical Sol: 1mL, 4%, 40mg
    Lidocaine/Lidocaine Hydrochloride/Xylocaine MPF Retrobulbar Inj Sol: 4%
    Lidocaine/Lidocaine Hydrochloride/Xylocaine MPF Topical Inj Sol: 4%
    Lidocaine/Lidocaine Hydrochloride/Xylocaine/Xylocaine MPF Epidural Inj Sol: 0.5%, 1%, 1.5%, 2%
    Lidocaine/Lidocaine Hydrochloride/Xylocaine/Xylocaine MPF Infiltration Inj Sol: 0.5%, 1%, 1.5%, 2%
    Lidocaine/Lidocaine Hydrochloride/Xylocaine/Xylocaine MPF Intracaudal Inj Sol: 1%, 1.5%, 2%
    Lidocaine/Lidocare Transdermal Film: 4%
    Lidocaine/Lidoderm Transdermal Film ER: 5%
    Lidocaine/MENTHO-CAINE/SOLUPAK Topical Ointment: 5%
    Xylocaine Percutaneous Inj Sol: 0.5%, 1%
    Xylocaine Urethral Jelly: 2%
    Zingo Intradermal Pwd: 0.5mg

    DOSAGE & INDICATIONS

    For the treatment of perfusing ventricular arrhythmias including ventricular fibrillation (VF) and ventricular tachycardia (VT) that may result during acute myocardial infarction or cardiac manipulation (e.g., cardiac surgery).
    NOTE: See resuscitation indication for dosage guidelines for VF or pulseless VT.
    NOTE: Although not considered a drug of choice for ventricular arrhythmias, lidocaine may be used as an alternative antiarrhythmic in patients with preserved ventricular function and stable monomorphic VT. Lidocaine may also be used to treat polymorphic VT in patients with a normal QT interval (when electrolyte imbalance and ischemia are treated). If pulseless cardiac arrest associated with VF or VT, see separate dosage guidelines for the treatment ventricular arrhythmias during CPR.
    NOTE: Lidocaine may be used to treat patients with polymorphic VT associated with QT prolongation (e.g., torsade de pointes).
    NOTE: Monitor blood pressure and the electrocardiogram (ECG) during intravenous lidocaine administration.
    Loading dose.
    Intravenous dosage (Injection)
    Adults

    Initially, 50 to 100 mg IV given at a rate of approximately 25 to 50 mg/minute; monitor ECG during administration. If needed, a second dose may be repeated in 5 minutes; the maximum loading dose is 300 mg IV administered over a 1 hour period. Alternatively, for perfusing ventricular tachycardia, initially 0.5 to 0.75 mg/kg IV and up to 1 to 1.5 mg/kg IV; may repeat 0.5 to 0.75 mg/kg IV every 5 to 10 minutes up to a maximum total loading dose of 3 mg/kg IV.

    Children

    1 mg/kg IV loading dose; administer slowly. Additional boluses may be given every 5 to 10 minutes if needed; up to 3 mg/kg total for loading dose.

    Intramuscular dosage
    Adults

    300 mg IM has been administered in the pre-hospital setting. Intramuscular lidocaine should not be used in the presence of shock due to potential unreliable systemic absorption.

    Maintenance dose.
    NOTE: Intravenous infusion should be terminated as soon as the cardiac rhythm stabilizes or if toxicity occurs. It is rarely necessary to continue IV infusions more than 24 hours. When feasible, switch to an oral antiarrhythmic agent for maintenance therapy.
    Intravenous dosage (Continuous Infusion)
    Adults

    1 to 4 mg/minute (20 to 50 mcg/kg/minute) IV infusion is recommended by the manufacturer; monitor ECG during administration. Clinical practice guidelines for ventricular tachycardia (with pulse) recommend a similar dosage regimen of 1 to 4 mg/minute (30 to 50 mcg/kg/minute) IV infusion. Use lower infusion rates for patients with heart failure or hepatic disease, patients older than 70 years, or debilitated patients. Arrhythmia breakthrough can be treated with a bolus dose of 0.5 mg/kg IV and an increase in the infusion rate, up to 4 mg/minute IV. If the infusion is continued more than 24 hours, a decrease in the maintenance infusion rate may be needed to avoid systemic drug accumulation.

    Children

    20 to 50 mcg/kg/minute IV infusion. Reduce the maintenance infusion rate in patients with shock, hepatic disease, or heart failure. If the infusion is initiated more than 15 minutes since a bolus loading dose of lidocaine, administer a 1 mg/kg IV loading dose when the continuous infusion is initiated.

    For topical anesthesia of skin and mucous membranes or stomatitis.
    For prevention of dental pain† and for topical anesthesia of mucous membranes.
    Transmucosal dosage (DentiPatch system)
    Adults, Adolescents, and Children 12 years and older

    Isolate the procedure area with cotton rolls; dry the tissue with air or gauze. Apply the patch to the desired area using firm pressure. Allow the patch to remain in place until the desired anesthetic effect is produced but for no longer than 15 minutes. Anesthesia usually occurs within 2.5 minutes of application, is present for the duration of a 15 minute application period, and persists for approximately 30 minutes after patch removal.

    Children younger than 12 years†

    An application time of 5 minutes was used in small pharmacokinetic study in children (n = 11, age 2 to 7 years). Apply patch to the local area of gingiva or mucosa before palatal injection, then remove the patch. Do not inject through the patch. Before scaling and root planing, apply to the buccal and lingual side of the molar, then to the premolar areas in the quadrant being worked on. Allow 5 to 10 minutes after applying the system before beginning any procedures. In adult patients, anesthesia continues for 30 to 40 minutes after system removal after a 15 minute application time.

    For laryngoscopy.
    Topical dosage (4% solution)
    Adults

    Spray the pharynx with 1 to 5 mL (40 to 200 mg or 0.6 to 3 mg/kg).

    For nonurgent painful procedures including IV cannulation, venipuncture, lumbar puncture, or arterial puncture.
    Topical dosage (Zingo)
    Adults, Adolescents, and Children 3 years and older

    0.5 mg (1 actuation) to intact skin 1 to 3 minutes before venipuncture or peripheral IV cannulation. After administration, perform the procedure within 10 minutes. Application of 1 additional actuation (0.5 mg) at a new location is acceptable after a failed attempt at venous access. Multiple administrations of a dose at the same location are not recommended.

    Topical dosage (4% cream; e.g., LMX 4)
    Children and Adolescents

    Apply 2 to 2.5 g for 20 to 60 minutes before procedure and cover with an occlusive dressing (Max application time: 2 hours).

    Neonates† and Infants†

    Apply 1 g for 20 to 40 minutes before procedure and cover with an occlusive dressing (Max application time: 1 hour).

    For the treatment of stage 1 thru 4 pressure ulcers, venous stasis ulcers, ulcerations of mixed vascular etiologies, diabetic skin ulcers, first and second degree burns, and post surgical incisions, cuts, and abrasions.
    Topical dosage (LDO Plus 4% Hydrogel Wound Dressing)
    Adults, Adolescents, and Children 2 years and older

    Apply a thin layer of gel to the wound surface and the immediate surrounding skin 3 to 4 times daily.

    For endotracheal intubation.
    Topical dosage (4% solution)
    Neonates†, Infants, Children, and Adolescents

    4 mg/kg of 4% lidocaine solution was administered via 2 different methods to 490 patients (age 0 to 16 years) undergoing elective endotracheal intubation. Lidocaine was administered to 1 group via a spray onto the vocal cords using an atomizer under direct laryngoscopy (n = 254). The other group received lidocaine dripped out of a syringe over the base of the tongue blindly into the pharynx (n = 236). There were no differences in respiratory adverse reactions during the perioperative period between the 2 methods of administration; however, patients who received lidocaine before intubation had significantly more desaturations (SpO2 less than 95%) during induction and recovery compared to patients who did not receive lidocaine (n = 510, 14.7% vs. 9.2%, p less than 0.01).

    Topical dosage (jelly)
    Infants, Children, and Adolescents

    Apply a moderate amount of jelly to the external surface of the endotracheal tube shortly before use. Do not exceed a maximum lidocaine dose of 4.5 mg/kg. Avoid getting any of the jelly into the lumen of the tube in order to prevent occlusion. Do not use jelly to lubricate endotracheal stylettes.

    For neonatal circumcision†.
    Topical dosage (4% cream; e.g., LMX 4)
    Neonates

    Apply 2 g topically to the foreskin for 20 minutes before procedure and cover with an occlusive dressing. Topical 4% lidocaine is the preferred topical local anesthetic for neonatal circumcision because of a faster onset of action, no risk of methemoglobinemia, and less risk of minor skin reactions or blistering as compared with lidocaine; prilocaine cream.

    For bronchoscopy.
    Topical dosage
    Infants and Children

    An initial dose of 5 mg/kg of 1.5% lidocaine solution diluted with 0.9% Sodium Chloride Injection to a final volume of 10 to 20 mL was used in a small study (n = 15, age 3 months to 9.5 years) during bronchoscopy. The dose was administered to various parts of the airway via the bronchoscope. The mean dose required to provide anesthesia throughout the procedure was 5.7 mg/kg (range 3.2 to 8.5 mg/kg). Higher doses (7 mg/kg or more) were only used in patients undergoing longer procedures and were given over 20 to 45 minutes. The mean lidocaine Cmax was 2.5 mcg/mL (range 1 to 3.5 mcg/mL); no patients had toxic serum concentrations (6 mcg/mL or more).

    Nebulized dosage†
    Infants, Children, and Adolescents

    4 to 8 mg/kg of 2% lidocaine solution was administered via nebulization in a small study (n = 20, age 1.5 months to 16 years) of patients immediately before bronchoscopy. Doses with a volume less than 3 mL were further diluted with 0.9% Sodium Chloride Injection. Supplemental doses were administered via syringe into the nose or via bronchoscope at the discretion of the bronchoscopist. The total dose range required during the procedure was 4 to 19.6 mg/kg; 10 patients did not require any supplemental lidocaine. The maximum serum lidocaine concentration observed was 2.27 mcg/mL after a total dose of 16.9 mg/kg; no patients experienced toxic serum concentrations.

    Topical dosage (ointment, jelly, gel, solution)
    Adults, Adolescents, Children, and Infants

    The dosage required varies depending on the area to be anesthetized, the vascularity of the tissue, individual tolerance, and anesthetic technique. Apply to affected area as needed for adequate control of symptoms, not to exceed a total lidocaine dose of 4.5 mg/kg (Max: 300 mg). Use of a sterile gauze pad is recommended for application of the ointment to broken skin tissue. For the lidocaine 3% gel, apply a thin film to the affected area 2 to 3 times daily (Max: 12 pumps from the airless pump bottle/day; 1 pump covers an area 2 by 2 inches); do not exceed 4.5 mg/kg of lidocaine (Max: 300 mg).

    Topical dosage (rectal cream)
    Adults, Adolescents, and Children 12 years and older

    Apply to affected area up to 6 times per day.

    Topical dosage (OTC cream, gel, spray, solution)
    Adults, Adolescents, and Children 2 years and older

    Apply to affected area of skin no more than 3 to 4 times per day. Avoid application of large quantities especially over raw or blistered areas.

    Topical dosage (2% viscous solution)
    Adults

    15 mL/dose; swish and spit solution for use in the mouth or gargle and swallow for use in the pharynx. Separate doses by at least 3 hours (Max: 8 doses/day). A single dose of lidocaine should not exceed 4.5 mg/kg (Max: 300 mg).

    Children and Adolescents 4 to 17 years

    A single dose of lidocaine should not exceed 4.5 mg/kg (Max: 300 mg); swish and spit solution for use in the mouth or gargle and swallow for use in the pharynx. Separate doses by at least 3 hours (Max: 8 doses/day). Do NOT use to treat teething pain in young children due to the risk of serious adverse reactions, including seizures, severe brain injury, heart problems, and death.

    Infants and Children 3 years and younger

    1.2 mL (24 mg) applied to the affected area with a cotton-tipped applicator. Separate doses by at least 3 hours (Max: 4 doses/12 hours). Limit use to those situations where safer alternatives are not available or have failed. Do NOT use to treat teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, severe brain injury, heart problems, and death.

    Topical dosage (Lidocare 4% Pain Relief Patch Back/Shoulder)
    Adults and Adolescents

    Apply patch to affected area every 8 to 12 hours. Leave patch in place for up to 8 but no more than 12 hours.

    For the treatment of pain associated with postherpetic neuralgia.
    NOTE: Lidocaine dermal patch has been designated an orphan drug by the FDA for this indication.
    Dermal topical patch dosage (Lidoderm)
    Adults

    Apply up to 3 patches to intact skin to cover the most painful area for up to 12 hours in a 24-hour period. Patches may be cut into smaller sizes with scissors before removal of the release liner.

    Intravenous dosage†
    Adults

    1 mg/kg IV over 2 hours. In a randomized, double-blind, placebo-controlled, crossover study of patients with pain and allodynia of postherpetic neuralgia (n = 24) who failed to respond to conventional treatments, significant reductions from baseline in mean visual analog scores (VAS) for ongoing pain were demonstrated with placebo and lidocaine infusions (1 mg/kg or 5 mg/kg IV over 2 hours). VAS scores for dynamic pressure-provoked pain and the area of allodynia were significantly reduced from baseline with both lidocaine infusions whereas no significant difference was noted with placebo. Plasma lidocaine concentrations did not correlate with pain score. The low-dose infusion (1 mg/kg) produced lidocaine concentrations well below concentrations that are associated with cardiovascular adverse events, but several patients receiving lidocaine 5 mg/kg reached toxic lidocaine concentrations.

    For ophthalmic anesthesia.
    Regional dosage (4% Xylocaine-MPF sterile solution)
    Adults

    For retrobulbar injection the dose is 3—5 ml (120—200 mg or 1.7—3 mg/kg). A portion of this dose is injected retrobulbarly and the rest may be used to block the facial nerve.

    Ophthalmic dosage (Akten 3.5% ophthalmic gel)
    Adults

    Two drops applied to the ocular surface in the area of the planned procedure. Additional doses may be used to maintain anesthesia.

    For local anesthesia including peripheral nerve block anesthesia.
    NOTE: In adults, the dosages for local anesthesia reported are general guidelines only. The actual dose depends on a variety of factors such as depth of anesthesia, extent of surgical procedure, degree of muscle relaxation required, duration of anesthesia and the patients' physical condition. See Lidocaine; epinephrine monograph for information concerning combination dosing.
    For dental anesthesia including mandibular nerve block and maxillary infiltration.
    Regional dosage
    Adults

    20—100 mg (1—5 ml of a 2% solution).

    Children and Infants

    4—5 mg/kg or 100—150 mg as a single dose. For children < 10 years, it is rarely necessary to administer more than 0.9—1 ml (18—20 mg) per procedure to achieve local anesthesia for a procedure involving a single tooth. For maxillary infiltration, this amount may suffice to treat 2—3 teeth. During mandibular block, this amount will allow treatment of teeth in an entire quadrant. For infants, lidocaine concentrations of 0.25% are recommended.

    For infiltration anesthesia.
    Regional dosage
    Adults

    5—300 mg (up to 60 ml of 0.5% solution or 30 ml of a 1% solution) for percutaneous anesthesia. 50—300 mg (10—60 ml of 0.5% solution) for intravenous regional infiltration anesthesia.

    For intravenous regional anesthesia.
    Intravenous dosage
    Adults

    50—300 mg (10—60 ml of a 0.5% solution) IV.

    For pudendal nerve block.
    Regional dosage
    Adults

    100 mg (10 ml of a 1% solution) per side.

    For paravertebral block.
    Regional dosage
    Adults

    30—50 mg (3—5 ml of a 1% solution).

    For intercostal nerve block.
    Regional dosage
    Adults

    30 mg (3 ml of a 1% solution).

    For brachial plexus block.
    Regional dosage
    Adults

    225—300 mg (15—20 ml of a 1.5% solution).

    For paracervical block.
    Regional dosage
    Adults

    200 mg total dose. One-half of the total dose is administered to each side. Inject slowly, five minutes between sides.

    For sympathetic nerve block.
    For cervical stellate ganglion block.
    Regional dosage
    Adults

    50 mg (5 mL of a 1% solution).

    For lumbar sympathetic block.
    Regional dosage
    Adults

    50 to 100 mg (5 to 10 mL of a 1% solution).

    For epidural anesthesia.
    NOTE: The dose is determined by the number of dermatomes to anesthetized (2 to 3 mL/dermatome). The suggested concentrations and volumes serve as a guide, other volumes and concentrations may be used provided the maximum dose is not exceeded.
    For lumbar anesthesia.
    Epidural dosage
    Adults

    Total dose is usually 200 to 300 mg (10 to 15 mL of a 2% solution) or 225 to 300 mg (15 to 20 mL of a 1.5% solution). For continuous epidural anesthesia, the dose should be given at intervals of at least 90 minutes.

    For lumbar analgesia for severe pain.
    Epidural dosage
    Adults

    250 to 300 mg (25 to 30 mL of a 1% solution).

    For thoracic.
    Epidural dosage
    Adults

    Total dose is usually 200 to 300 mg (20 to 30 mL of a 1% solution). For continuous epidural anesthesia, the dose should be given at intervals of at least 90 minutes.

    For caudal anesthesia.
    For obstetric anesthesia.
    Regional dosage
    Adults

    200 to 300 mg (20 to 30 mL of a 1% solution). For continuous caudal anesthesia, the dose should be given at intervals of at least 90 minutes.

    For surgical anesthesia.
    Regional dosage
    Adults

    225 to 300 mg (15 to 20 mL of a 1.5% solution). For continuous caudal anesthesia, the dose should be given at intervals of at least 90 minutes.

    For spinal anesthesia.
    For obstetrical low spinal or saddle block anesthesia.
    Regional dosage (5% Xylocaine MPF with glucose 7.5% injection)
    Adults and Adolescents >= 16 years

    For vaginal delivery, 1 ml (50 mg) of 5% solution. For caesarean section and those deliveries requiring intrauterine manipulations, use 1.5 ml (75 mg) of 5% solution.

    For intraabdominal anesthesia.
    Regional dosage (5% Xylocaine MPF with glucose 7.5% injection only)
    Adults and Adolescents >= 16 years

    1.5—2 ml (75—100 mg ) of 5% solution.

    For the treatment of ventricular arrhythmias during cardiopulmonary resuscitation† (CPR).
    Intravenous or Intraosseous† dosage
    Adults

    Initially, 1 to 1.5 mg/kg IV. If ventricular fibrillation or pulseless ventricular tachycardia persist, additional 0.5 to 0.75 mg/kg IV doses can be given every 5 to 10 minutes up to a total loading dose of 3 mg/kg. The same dose may be given via the intraosseous route when IV access is not available. There is inadequate evidence to support the routine use of lidocaine after cardiac arrest; however, the initiation or continuation of lidocaine may be considered after return of spontaneous circulation (ROSC) from cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia. If a maintenance lidocaine infusion is warranted for an individual patient, administer 1 to 4 mg/minute (30 to 50 mcg/kg/minute) IV. Use lower infusion rates for patients who are elderly, have heart failure or hepatic disease, or are debilitated. Lidocaine is considered an alternative antiarrhythmic to amiodarone for this indication, particularly when amiodarone is not available. Lidocaine is convenient to administer but is not as effective as amiodarone for improving ROSC or survival to hospital admission among adult patients with VF refractory to a shock and epinephrine. Neither drug has been shown to improve survival to hospital discharge in cardiac arrest patients with VF.

    Neonates, Infants, Children, and Adolescents

    1 mg/kg IV or IO loading dose (Max: 100 mg) followed by a continuous infusion of 20 to 50 mcg/kg/minute. May repeat bolus dose if more than 15 minutes has passed between the initial bolus and the start of the infusion. A maximum infusion rate of 20 mcg/kg/minute IV has been recommended in patients who are in shock, have heart failure, or are in cardiac arrest. Either lidocaine or amiodarone can be used for shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Pediatric observational data has shown improved return of spontaneous circulation (ROSC) with the use of lidocaine as compared with amiodarone. In addition, use of lidocaine compared with no lidocaine was significantly associated with an increased likelihood of ROSC. Neither lidocaine nor amiodarone has been shown to improve survival to hospital discharge. Lidocaine is also recommended by the Pediatric Advanced Life Support (PALS) algorithm to prevent arrhythmias secondary to myocardial infarction in patients with cocaine overdose.

    Endotracheal dosage†
    Adults

    2 to 4 mg/kg via endotracheal (ET) tube (2 to 2.5 times the IV dosage). Dilute dose in 5 to 10 mL of 0.9% Sodium Chloride Injection or Sterile Water for Injection. Based on data with epinephrine and lidocaine, ET drug absorption may be improved by diluting with sterile water for injection instead of 0.9% Sodium Chloride Injection. ET administration is associated with lower blood drug concentrations compared to IV administration and may be unreliable. Therefore, ET administration should be used only if access to IV or IO routes cannot be achieved or when access is delayed.

    Neonates, Infants, Children, and Adolescents

    2 to 3 mg/kg via endotracheal (ET) tube. After administration, flush ET tube with at least 5 mL of 0.9% Sodium Chloride Injection and deliver 5 consecutive positive-pressure ventilations. Based on data with epinephrine and lidocaine in adults, ET drug absorption may be improved by diluting with Sterile Water for Injection instead of 0.9% Sodium Chloride Injection. ET tube administration is associated with lower blood drug concentrations compared to IV administration and may be unreliable. Therefore, only use ET tube administration if access to IV or IO routes cannot be achieved or when access is delayed.

    For the attenuation of increased intracranial pressure† during rapid-sequence intubation† or endotracheal tube suctioning†.
    During rapid-sequence intubation in patients with traumatic brain injury (TBI).
    Intravenous dosage
    Adults

    Limited data are available and use is controversial. Clinical trials examining the use of lidocaine during rapid sequence intubation (RSI) in patients with TBI have not been published. Some clinicians recommend 1.5 mg/kg IV given 2 minutes prior to intubation based on a study of 20 patients with cerebral neoplasms. In this placebo-controlled trial, the patients underwent endotracheal intubation for elective neurosurgery and were given lidocaine or placebo at the time of induction. All patients experienced an increase in ICP associated with intubation, but the authors report a 12 mmHg smaller increase in patients who received lidocaine compared to those who received placebo. Other clinicians caution against the use of lidocaine during RSI citing a lack of data and concern for a potential reduction in mean arterial pressure, which may lead to a reduction in cerebral perfusion pressure (CPP).

    Infants, Children, and Adolescents

    Clinical trials have not been published; however, 1—3 mg/kg IV given 2—5 minutes prior to laryngoscopy has been recommended.

    Associated with endotracheal suctioning in patients with closed head injury.
    Intravenous dosage
    Adults

    Limited data suggest that 1.5 mg/kg IV administered prior to suctioning may attenuate the rise in intracranial pressure (ICP) associated with endotracheal suctioning. A randomized, double-blind, cross-over trial of 10 patients with closed head injury compared IV lidocaine to saline. All patients were receiving mechanical ventilation and experienced ICPs of > 20 torr in response to endotracheal suctioning prior to study initiation. After the administration of lidocaine or saline, all patients continued to experience an increase in ICP in response to suctioning. However, the authors concluded that the mean peak increase in ICP was lower in the lidocaine group. There were no significant changes in mean arterial pressure associated with lidocaine administration. Another trial of 9 patients with severe head injury compared 1.5 mg/kg IV lidocaine to 2 ml of 4% lidocaine administered intratracheally prior to endotracheal suctioning. Neither IV nor intratracheal lidocaine reduced the baseline ICP; however, both treatments suppressed an acute rise in ICP during suctioning. The mean peak ICP after suctioning was lower in the intratracheal group compared to the IV group (p < 0.01).

    Endotracheal dosage
    Adults

    Limited data are available. A trial of 9 patients with severe head injury compared 1.5 mg/kg IV lidocaine to 2 ml of 4% lidocaine administered intratracheally prior to endotracheal suctioning. The intratracheal dose was administered through a 4 French tube inserted near the carina. Neither IV nor intracheal lidocaine reduced the baseline ICP; however, both treatments suppressed an acute rise in ICP during suctioning. The mean peak ICP after suctioning was lower in the intratracheal group compared to the IV group (p < 0.01).

    For the treatment of severe singultus (hiccups)†.
    Intravenous dosage
    Adults

    A single case report is noted in which IV lidocaine successfully aborted severe hiccups. A loading dose of 1 mg/kg IV followed by a continuous infusion of 1 mg/minute initially was given, followed by additional boluses to yield a total loading dose of 2 mg/kg and an increase in the rate to 4 mg/minute. Within 1 hour, the patient was able to eat and speak without interruption. Lidocaine was discontinued after 24 hours and the hiccups returned. A second infusion of lidocaine at 2 mg/minute was successful. After 24 hours, lidocaine was discontinued and the patient was given oral carbamazepine for 2 weeks. Hiccups did not recur after carbamazepine was discontinued.

    For the treatment of headache†.
    For the treatment of acute headache† associated with migraine†.
    Intranasal dosage (An intranasal dosage form is not available in the US)†
    Adults

    Lidocaine, instilled intranasally, was superior to placebo in a randomized, double-blind study for the treatment of migraine headache. Lidocaine provided significant relief of headache pain, nausea, and photophobia within 5 minutes compared to placebo. Fifty-five percent of lidocaine patients compared to 21% of controls had at least a 50% reduction in headache intensity. Among those with initial relief, 24% of the lidocaine group relapsed within the first hour after treatment compared with 83% of the placebo group. In this study, topical lidocaine 4% solution was used. A dose of 0.5 mL was dripped into the nostril on the same side as the migraine. If the headache was bilateral, both nostrils were treated.

    For the treatment of cluster headache†.
    Intranasal dosage (An intranasal dosage form is not available in the US)†
    Adults

    Lidocaine, administered as a 4% intranasal spray, was offered to 30 male patients with cluster headache. Four sprays were used initially, followed by 2 additional sprays repeated in 15 minutes, if necessary. The patient was instructed to extend the head 45 degrees, bent ipsilateral to the pain. To overcome nasal congestion prior to lidocaine, 0.5% phenylephrine nasal spray was used. Although the study was not blinded or randomized, the efficacy was marginal. Forty-six percent of patients experienced no relief. Twenty-seven percent experienced mild or moderate relief, respectively. No patient experienced excellent relief.

    For the symptomatic treatment of corticosteroid-dependent asthma†.
    NOTE: Initial bronchoconstriction can occur. In addition, lidocaine toxicity can result in tremors, hallucinations, seizures, and cardiac arrest. Caution is advised until long-term safety and efficacy can be established.
    Inhalational dosage (An inhalational dosage form is not available in the US)
    Adults

    100 mg (2.5 ml of 4% injectable lidocaine without preservatives) was administered via inhalation four times daily for 8 weeks in a randomized, placebo-controlled study. Fifty subjects with mild to moderate asthma receiving inhaled corticosteroids were randomized to receive active drug or placebo (i.e., nebulized saline). Subjects were instructed not to eat or drink for 1 hour following treatment due to diminished cough and gag reflexes. Study results indicated that significant improvement occurred in the lidocaine group in symptom scores, nighttime awakenings, bronchodilator use, FEV1 in liters, FEV1 percent predicted, and blood eosinophils compared to those receiving placebo. Most subjects in the lidocaine group had discontinued corticosteroid use by the end of the study. Results from a small open-label study suggested benefits of nebulized lidocaine in allowing reduction or elimination of oral corticosteroids in severe, steroid-dependent asthmatics. Further study is needed to confirm these findings.

    Children and Adolescents 8—14 years

    Very limited data are available from a case report and open-label trial. Nebulized doses of 40—100 mg (0.8—2.5 mg/kg/dose) were administered three to four times daily to 6 pediatric patients with severe, glucocorticoid-dependent asthma. All patients were asked not to eat or drink for 30 minutes prior to and 1 hour following treatment due to the local anesthetic effects of the drug. Discontinuation of oral glucocorticoids was achieved in 5 of 6 patients between 1—7 months, although 'short bursts' of steroids were needed for some acute exacerbations. The duration of treatment was patient-specific (7—16 months). One patient did not improve and discontinued treatment after 7 months. Side effects included bitter taste and transient oropharyngeal anesthesia. In a separate report, inhaled lidocaine 100 mg (2.5 mg/kg/dose) four times a day was effective in one 12 year old patient with frequent and severe asthma attacks. Improvements included a decrease in symptoms and exercise-induced bronchospasm, decreased rescue treatment (i.e., beta-2 agonists), discontinuation of routine oral corticosteroid use, improvement in PEFR, and improvement in predicted FEV1 up to 30% after 18 months of treatment. This preliminary evidence suggests that lidocaine may have steroid-sparing actions in some severely asthmatic pediatric patients; however, further study is needed to confirm these findings and to determine long-term safety and efficacy.

    For short-term prophylaxis of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing† (SUNCT).
    Continuous IV Infusion dosage
    Adults

    Results from limited observational studies and case series suggest a dose of 1 to 3 mg/minute continuous IV infusion for 1 to 14 days is effective in providing relief from SUNCT symptoms; however, side effects such as nausea, vomiting, depression, and vivid dreams caused some patients to discontinue treatment. One author recommends not exceeding 7 days of lidocaine treatment. In a case report, a 70-year-old man experienced almost complete resolution of SUNCT symptoms after 10 minutes of 1.3 mg/kg/hour continuous IV infusion. He received the medication for 21 days and was discharged pain-free on lamotrigine.

    Continuous Subcutaneous Infusion dosage
    Adults

    Results from a case series suggest a dose of 2 mg/minute via continuous subcutaneous infusion for an average of 6 to 8 days may be effective at ceasing SUNCT symptoms. In this study, patients receiving subcutaneous had similar efficacy to patients receiving IV administration of lidocaine (79% effective for subcutaneous vs. 67% for IV, p value not reported).

    For the treatment of painful diabetic neuropathy† in adults.
    Dermal topical patch dosage (e.g., Lidoderm 5% patch or therapeutic equivalents)
    Adults

    Optimal dosage has not been determined. Apply up to 4 patches topically to the most painful area (Max recommended by manufacturer: 3 patches to the most painful area ). Wear for up to 12 hours within a 24-hour period ; however, some studies allowed patches to remain in place for up to 18 hours. American Academy of Neurology clinical practice guidelines consider the lidocaine patch as possibly effective in lessening the pain of diabetic neuropathy; use as a treatment option may be considered.

    †Indicates off-label use

    MAXIMUM DOSAGE

    NOTE: These refer to lidocaine use as a local anesthetic.
    NOTE: The dose of local anesthetics differs with the anesthetic procedure; the area to be anesthetized; the vascularity of the tissues; the number of neuronal segments to be blocked; the intensity of the block; the degree of muscle relaxation required; the duration of anesthesia desired; individual tolerance; and the physical condition of the patient.

    Adults

    4.5 mg/kg or 300 mg per procedure when used as a local anesthetic without epinephrine. For continuous epidural or caudal epidural anesthesia, the maximum dosage should not be administered at intervals less than 90 minutes. When continuous lumbar or caudal epidural anesthesia is used for non-obstetrical patients, more drug may be administered if needed to achieve adequate anesthesia. The maximum dose for paracervical block in obstetrical and non-obstetrical patients is 200 mg (100 mg per side) in a 90 minute period. For intravenous regional anesthesia, the dose should not exceed 4 mg/kg. The total dose contributed by all formulations should be considered. For Zingo, 2 actuations (0.5 mg/actuation) at different sites.

    Geriatric

    4.5 mg/kg or 300 mg per procedure when used as a local anesthetic without epinephrine. For continuous epidural or caudal epidural anesthesia, the maximum dosage should not be administered at intervals less than 90 minutes. When continuous lumbar or caudal epidural anesthesia is used for non-obstetrical patients, more drug may be administered if needed to achieve adequate anesthesia. The maximum dose for paracervical block in obstetrical and non-obstetrical patients is 200 mg (100 mg per side) in a 90 minute period. For intravenous regional anesthesia, the dose should not exceed 4 mg/kg. The total dose contributed by all formulations should be considered. For Zingo, 2 actuations (0.5 mg/actuation) at different sites.

    Adolescents

    For Zingo, 2 actuations (0.5 mg/actuation) at different sites.

    Children

    11 years or more: 4.5 mg/kg when used as a local anesthetic without epinephrine. For induction of intravenous regional anesthesia in children, dilute solutions (i.e., 0.25 to 0.5%) should be used and total dosages should not to exceed 3 mg/kg. For Zingo, 2 actuations (0.5 mg/actuation) at different sites. The total dose contributed by all formulations should be considered. 
    3 to 10 years: The maximum dose should be determined by the application of one of the standard pediatric drug formulas (i.e., Clark's rule) in children who have normal lean body mass and normal body development. For induction of intravenous regional anesthesia in children, use dilute solutions (i.e., 0.25 to 0.5%) and total dosages should not to exceed 3 mg/kg. For Zingo, 2 actuations (0.5 mg/actuation) at different sites. The total dose contributed by all formulations should be considered.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dosage adjustment may be required in some patients with hepatic dysfunction. No established guidelines are available.

    Renal Impairment

    No dosage adjustment needed. However, the elimination of glycinexylidide (major active metabolite) is eliminated renally, and accumulation of the metabolite in severe renal failure could theoretically result in neurotoxicity.
     
    Intermittent hemodialysis
    No dosage adjustment is needed in hemodialysis patients.

    ADMINISTRATION

    Injectable Administration

    For specific procedures and administration techniques, consult specialized references.
    Have resuscitative equipment and drugs for the management of adverse reactions immediately available.
    Administer intramuscularly or intravenously for cardiac arrhythmias and by infiltration or epidural (including caudal), peripheral, sympathetic, or spinal block techniques for anesthesia.
    Serum lidocaine concentrations may be used to guide parenteral therapy. Target serum concentration is approximately 2 to 6 mcg/mL. Monitor patients with heart failure or liver disease closely since lidocaine clearance is reduced in these patients.
    Do not use injections containing epinephrine to treat arrhythmias.
    Due to the risk of overdosage, injections containing 40 or 200 mg/mL should only be used for preparation of IV infusion solutions.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intravenous injection:
    Monitor blood pressure and the electrocardiogram during intravenous administration.
    Administer bolus injection at a rate of 25 to 50 mg/minute. May administer faster during cardiac arrest.
    During adult cardiopulmonary resuscitation (CPR): Administer bolus dose into a peripheral vein, followed by an injection of 20 mL IV fluid. Elevate the extremity for 10 to 20 seconds to facilitate drug delivery to the central circulation. Although peak concentrations are lower when drugs are administered via peripheral vs. central sites, the establishment of peripheral access does not require interruption of CPR. Drugs generally reach the central circulation within 1 to 2 minutes when administered peripherally but require less time when given via central venous access.
    During pediatric CPR: Administer bolus dose by rapid IV push.
     
    Intravenous infusion:
    Monitor blood pressure and the electrocardiogram during intravenous administration.
    Add 1 or 2 grams lidocaine to 1 L of 5% Dextrose Injection to obtain infusions with concentrations of 1 or 2 mg/mL. Alternatively, commercially available infusions of 2, 4, or 8 mg/mL in 5% Dextrose Injection may be used.
    Use an infusion pump to administer by continuous infusion.

    Intramuscular Administration

    Inject, preferably, deep into the deltoid muscle. The quadriceps muscle has also been used for injection.
    Aspirate prior to injection to avoid injection into a blood vessel.
    Intramuscular administration should not be used in the presence of shock due to potential unreliable systemic absorption.

    Other Injectable Administration

    Intradermal Injection (Zingo) system
    Each device contains 0.5 mg of sterile lidocaine hydrochloride monohydrate powder.
    Only use on skin locations where an adequate seal can be maintained. Do not use around the eyes, on body orifices, on mucous membranes, or on areas with a compromised skin barrier.
    Press the device against an intact area of skin. Ensure an adequate seal between the device and the skin. Pressing the device against the skin will release the safety interlock. Press the button to actuate the device.
    A popping sound like a burst balloon is heard when the device is actuated. Lidocaine is delivered to the dermis by a needle-free, helium-pressurized delivery system.
    Multiple administrations at the same location are not recommended.
     
    Intraosseous infusion†:
    NOTE: Lidocaine is not FDA-approved for intraosseous administration.
    During cardiopulmonary resuscitation, the same dosage may be given via the intraosseous route when IV access is not available.
     
    Dental, peripheral, or sympathetic block:
    Consult specialized references for proper injection technique.
    Inject slowly and with frequent aspirations to prevent intravascular injection. 
     
    Endotracheal (ET) Administration (e.g., Xylocaine-MPF Sterile Solution)
    Generally, the optimal dosage for endotracheal administration has not been established; higher doses may be required for some patients.
    Adults: Dilute dose in 5 to 10 mL of 0.9% Sodium Chloride Injection or Sterile Water for Injection. Administer via ET tube. Endotracheal absorption may be improved by diluting with water instead of 0.9% Sodium Chloride Injection.
    Children: After dose administration, flush the ET tube with a minimum of 5 mL of 0.9% Sodium Chloride Injection.
     
    Epidural Administration
    Only specially trained healthcare professionals should use this route of administration. Consult specialized references for specific procedures and administration techniques.
    Have resuscitative equipment and drugs used in the management of adverse reactions immediately available.
    May be given as a caudal block, epidural intermittent bolus, continuous infusion, or patient controlled epidural analgesia.
    Placement of epidural catheter and administration should be at a site near the dermatomes covering the field of pain to decrease dose requirements and increase specificity.
    Administer a test dose of 2 to 3 mL of 1.5% lidocaine 5 minutes before administering the total dose. Inadvertent subarachnoid injection is indicated by motor paralysis and extensive sensory anesthesia. If epinephrine is contained in the test dose, a transient increase in heart rate and systolic blood pressure (SBP), circumoral pallor, palpitations, and nervousness will occur in non-sedated patients if subarachnoid injection occurs. In sedated patients, a momentary increase in SBP will be detected.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Discard unopened solutions if a precipitate is present that does not disappear with shaking.
    Vials containing lidocaine alone may be autoclaved repeatedly if necessary.
     
    Epidural or caudal block:
    Do not use injections containing preservatives for epidural or caudal block. Discard any partially used injections that do not contain preservatives.
    Inject slowly with frequent aspirations. Monitor blood pressure during anesthesia. Use care to prevent intravascular or subarachnoid injection.
     
    Epidural infusion:
    Do not use injections containing preservatives for epidural infusion. Discard any partially used injections that do not contain preservatives.
    A controlled-infusion device must be used. For highly concentrated injections, an implantable controlled-microinfusion device is used. Monitor patients for several days following implantation of the device.
    Preservative-free 0.9% Sodium Chloride Injection is recommended for dilution.
    Implantable infusion device: Only fully trained and qualified healthcare professionals should fill the infusion device reservoir. Strict aseptic technique must be used. Withdraw dose from the ampule through a 5-micron (or smaller pore diameter) microfilter to avoid contamination with glass or other particles. Ensure proper placement of the needle when filling the reservoir to avoid accidental overdosage.
    To avoid exacerbation of severe pain and/or reflux of CSF into the reservoir, depletion of the reservoir should be avoided.
     
    Spinal Administration (Xylocaine-MPF with Glucose 7.5% Injection)
    This route should only be used by specially trained healthcare professionals. Specialized references should be consulted for specific procedures and administration techniques.
    Resuscitative equipment and drugs used in the management of adverse reactions should be immediately available while administering spinal anesthesia.
    Injections containing preservatives should not be used. Prior to using, the outside of ampules should be sterilized, preferably by autoclaving.
    Do not autoclave ampules more than once since the formulation contains glucose, caramelization may occur under prolonged heating and, in some instances, prolonged storage.
    Do not use solution if it is discolored or a precipitate is present.
    Discard any partially used injections that do not contain preservatives.
     
    Spinal block:
    Spinal anesthesia may be induced in the right or left lateral recumbent position or the sitting position. Since this is a hyperbaric solution, the anesthetic will tend to move in the direction in which the table is tilted.
    Administer via 22 or 25 gauge spinal needles. Monitor blood pressure during administration.
    Mixing lidocaine with an equal volume of CSF or preservative-free 0.9% Sodium Chloride Injection may reduce the risk of nerve injury due to pooling of the concentrated local anesthetic.
    After the desired level of anesthesia is obtained and the anesthetic has become fixed, usually within 5 to 10 minutes, the patient may be positioned appropriately.

    Topical Administration

    Have resuscitative equipment and drugs for the management of adverse reactions immediately available while administering local anesthetics to mucous membranes.

    Cream/Ointment/Lotion Formulations

    Ointment:
    Skin: If used on broken skin, apply using a sterile gauze pad.
    Dental use: Apply to dried oral mucosa. Subsequent removal of excess saliva with cotton rolls or saliva ejector minimizes dilution of the ointment, permits maximum penetration, and minimizes the possibility of swallowing. For denture fitting, apply to all denture surfaces contacting the mucosa.
    Intubation: Apply to the tube prior to intubation. Be sure to avoid putting ointment into the lumen of the tube.

    Transdermal Patch Formulations

    Dermal Patch (Lidoderm)
    Keep the patches in their sealed envelopes until immediately before use.
    After removing the patch from the protective envelope, immediately apply to intact skin to cover the most painful area. Do not expose the eyes.
    Patches may be cut into smaller sizes prior to removal of the release liner.
    Adherence of the patch may be affected by contact with water; advise patients to avoid activities such as bathing, swimming, or showering while wearing the patch.
    Wash hands after handling the patches. Fold the sticky side of used patches together, and dispose of in such a way as to prevent accidental exposure to children or pets.
     
    Dermal Patch (Lidocare)
    Clean and dry the affected area.
    Remove the patch from the pouch and remove the clear, protective liner.
    Apply patch to affected area.
    Wash hands thoroughly after applying or removing the patch.
    Do not use other local anesthetics while using the patch.
     
    Transoral Delivery System
    Isolate the procedure area with cotton rolls; use suction as appropriate.
    Dry area of application with air or gauze for 30 seconds. Drying time may be reduced when administering palatal injections.
    Remove protective liner and apply the system with firm finger pressure. Hold in place for 30 seconds. This allows the patch to properly conform and adhere to the gingiva and mucosa.
    Leave patch in place for a minimum of 5 to 10 minutes. Confirm the level of anesthesia by probing the site prior to beginning the procedure.
    Remove the system after 15 minutes using cotton pliers or fingers and dispose of properly. Based on a 15 minute application of the system, 30 to 40 minutes of continued anesthesia can be achieved.

    Other Topical Formulations

    Liquid:
    For topical use only. Do not inject parenterally.
    Apply using a swab. Discard swab after single use. The maximum single adult dose should not exceed 5 mL of 5% lidocaine liquid within any 3-hour period.
     
    Topical sterile solution:
    For topical use only.
    Topical solution may be sprayed or applied using cotton applicators or packs. When used as a spray, transfer topical solution from its original container to an atomizer.
     
    Viscous solution:
    For use in the mouth: Swish around in the mouth and spit out. For infants and children less than 3 years, apply the solution to the affected area using a cotton-tipped applicator. Do not use for the treatment of teething pain in infants and young children; 2% viscous lidocaine has been associated with serious adverse reactions, including seizures, severe brain injury, heart problems, and death.
    For use in the pharynx: Gargle with the undiluted solution and either swallow or spit out the solution. Do not administer more frequently than every 3 hours. Do not give more than 8 doses in any 24-hour period.
     
    Jelly:
    For urethral anesthesia: Follow manufacturer's direction for instillation into the urethra.
    For use in endotracheal intubation: Apply a moderate amount to the external surface of the tube. Be careful to avoid getting any of the jelly into the lumen of the tube in order to prevent occlusion. Do not use jelly to lubricate endotracheal stylettes.
     
    Hydrogel (LDO Plus 4% Hydrogel Wound Dressing):
    Cleanse the wound and blow it dry. Apply a thin layer of hydrogel to the skin and surrounding surface.

    Ophthalmic Administration

    Instruct patient on proper application of ophthalmic gel.
    Do not to touch the tip of the dropper to the eye, fingertips, or other surface.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store between 59 to 77 degrees F
    Akten :
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 59 to 77 degrees F
    - Store in original package until time of use
    ANASTIA:
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    AneCream:
    - Store at room temperature (between 59 to 86 degrees F)
    Anestacon:
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Aspercreme with Lidocaine:
    - Storage information not listed
    Astero :
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    CidalEaze:
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    EnovaRX:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in a cool, dry place
    Glydo:
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)
    LidaMantle:
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Lidocare:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lidoderm:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    LIDO-K :
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Lidomar :
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    LidoRx:
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Lidosense 4 :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    LMX 4:
    - Store at room temperature (between 59 to 86 degrees F)
    LMX 4 with Tegaderm:
    - Store at room temperature (between 59 to 86 degrees F)
    LMX 5:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    LTA:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    MENTHO-CAINE :
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Numbonex:
    - Protect from freezing
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Professional DNA Collection Kit:
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    RectaSmoothe:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    RectiCare:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Senatec:
    - Brief exposure up to 104 degrees F does not adversely affect product
    - Protect from freezing
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Solarcaine:
    - Store at room temperature (between 59 to 86 degrees F)
    SOLUPAK:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Tranzarel:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    VacuStim Silver:
    - Storage information not provided in labeling
    Xylocaine:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Xylocaine MPF:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Xylocaine Viscous:
    - Do not freeze
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Zilactin-L:
    - Store at room temperature (between 59 to 86 degrees F)
    Zingo:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Lidocaine application to oral mucosa can interfere with swallowing and increase the risk of aspiration. Patients should not ingest food for at least 1 hour after the use of anesthetic agents in the mouth or throat. 
     
    Local anesthetics, like lidocaine, should only be administered by a clinician trained in the diagnosis and management of drug-related toxicity and other acute emergencies that might arise from the administration of a regional anesthetic block. The immediate availability of oxygen, cardiopulmonary resuscitative equipment and drugs and the appropriate support personnel for the management of toxic reactions or emergencies must be ensured. Any delay in appropriate management may lead to the development of acidosis, cardiac arrest, and possibly death.

    Amide local anesthetic hypersensitivity, epidural anesthesia

    Lidocaine is contraindicated in patients with amide local anesthetic hypersensitivity. Parenteral preparations containing preservatives should not be used for spinal or epidural anesthesia. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products. There have been no reports of cross-sensitivity between lidocaine and either procainamide or quinidine.

    Collagen-vascular disease

    Lidocaine does not provide adequate anesthesia in patients with collagen-vascular disease, such as Ehlers Danlos Type III. Lidocaine is relatively contraindicated in these conditions.

    G6PD deficiency

    Lidocaine should be used with caution in patients with G6PD deficiency or pre-existing methemoglobinemia. As is reported in the literature, the use of topical or parenteral lidocaine may induce methemoglobinemia. Closely monitor predisposed patients who receive lidocaine. If symptoms of methemoglobinemia occur, hypoxia can be treated with oxygen therapy. Persistence of symptoms should be treated with methylene blue therapy.

    Geriatric, heart failure, hepatic disease

    Use lidocaine with caution in patients at increased risk of adverse events. Conditions that reduce hepatic blood flow such as hepatic disease and congestive heart failure may reduce hepatic metabolism and lead to drug accumulation, increasing the risk of developing systemic toxicity, particularly with parenteral, prescription topical jelly, or transdermal patch use. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated, particularly by those who are debilitated, pediatric patients, geriatric patients, or the acutely ill. Excessive dosing by applying lidocaine transdermal patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine and high blood concentrations, leading to serious systemic adverse effects. Lidocaine toxicity could be expected at lidocaine blood concentrations above 5 mcg/mL. The blood concentration of lidocaine is determined by the rate of systemic absorption and elimination. Longer duration of transdermal application, application of more than the recommended number of patches, smaller patients, or impaired elimination may all contribute to increasing the blood concentration of lidocaine. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. The OBRA guidelines caution that antiarrhythmics can have serious adverse effects (e.g., impairment of mental function, appetite, behavior, heart function, or falls) in older individuals.

    Hypotension, pregnancy

    Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women. Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure. When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary. A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.

    Breast-feeding

    According to the manufacturers, caution should be exercised when lidocaine is administered to breast-feeding women (regardless of dosage formulation). Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4. Many specific dosage forms, including Lidoderm brand lidocaine transdermal patches, have not been studied in breast-feeding women. The American Academy of Pediatrics lists lidocaine as usually compatible with breast-feeding. When lidocaine is used for dental or short-term, limited local anesthesia, the healthy term infant can generally safely nurse as soon as the mother is awake and alert. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternal drug exposure, healthcare providers are encouraged to report the adverse effect to the FDA.

    Adams-Stokes syndrome, atrial fibrillation, atrial flutter, AV block, bradycardia, cardiogenic shock, hemorrhagic shock, hypovolemia, shock, Wolff-Parkinson-White syndrome

    Although specific forms of parenteral lidocaine are indicated for the treatment of some cardiac arrhythmias, it can worsen others. Intravenous (IV) lidocaine for the treatment of ventricular arrhythmias is contraindicated in patients with Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, or with severe SA block, AV block, or intraventricular heart block. The administration of IV lidocaine for the elimination of ventricular ectopic beats to patients with bradycardia or incomplete heart block without prior acceleration of heart rate may cause a more serious ventricular arrhythmia or complete heart block. Lidocaine can increase the ventricular rate in patients with atrial fibrillation or atrial flutter. Use lidocaine with caution in patients with hypovolemia. Monitor blood pressure and the electrocardiogram during IV lidocaine administration. Promptly discontinue the infusion if signs of excessive depression of cardiac conductivity occur, such as prolongation of the PR interval, widening of the QRS interval, or appearance or aggravation of arrhythmias. Use both parenteral and topical formulations of lidocaine with caution in patients with severe shock (including cardiogenic shock and hemorrhagic shock) and heart block. Patients with impaired cardiac function, particularly AV block, may be less able to compensate for functional changes associated with prolonged AV conduction (i.e., PR or QT prolongation) caused by local anesthetics. Topical ocular application of lidocaine is not expected to result in systemic exposure.

    Renal disease, renal failure, renal impairment

    No lidocaine dosage adjustment needed in patients with renal impairment. However, the elimination of glycine xylidide (major active metabolite) is eliminated renally, and accumulation of the metabolite in severe renal failure (renal disease) theoretically could result in neurotoxicity.

    Burns, eczema, heating pad, occlusive dressing, skin abrasion

    Applying dermal, transdermal, or oromucosal lidocaine preparations to severely traumatized skin (e.g.,mucosal or skin abrasion, eczema, burns), to large surface areas, or to warm skin (i.e., exercise, or application of thermal heat wraps or a heating pad immediately before or during topical lidocaine use) can increase its absorption, possibly increasing the risk of systemic toxicity. Also, applying large amounts of lidocaine or using an occlusive dressing (skin wraps) can increase absorption. Patches and administration via Zingo injection system should only be used on intact skin, and transoral delivery systems should only be applied to intact mucosa. Excessive dosing by applying patches to larger areas or for longer than the recommended wearing time could result in increased absorption of lidocaine. Application of one additional Zingo at a new location is acceptable after a failed attempt at venous access. However, multiple administrations of Zingo at the same location are not recommended. Multiple Zingo applications could result in plasma concentrations that could produce systemic toxicity. At least 2 reports of deaths exist after application of topical anesthetics prior to cosmetic procedures. In both instances, women, aged 22 and 25 years, applied topical anesthetics to their legs and wrapped the treated area, as directed, in plastic wrap to enhance the numbing effect of the cream. Both women died from toxic effects of the topical anesthetic. The preparations used in both cases were compounded in pharmacies and contained high amounts of lidocaine and tetracaine. In order to reduce the risk of toxicity due to increased absorption of topical anesthetic, the FDA recommends patients use a topical anesthetic containing the lowest amount of medication needed to relieve pain, apply the medication sparingly, and only treat known or anticipated areas of pain. Further, do not apply the anesthetic to broken or irritated skin, be aware of potential adverse reactions, and do not cover or apply heat to the treated area.

    Cataracts, ocular exposure, ocular trauma

    Avoid unintended ocular exposure of lidocaine dermal, oromucosal, and transdermal products. Severe eye irritation has been reported in animals treated with similar products. If eye contact occurs, immediately wash the eye with water or saline and protect the eye until sensation returns. Lidocaine ophthalmic gel is intended for application to the eye surface; however, prolonged use may produce permanent corneal opacification and ulceration with accompanying visual loss. Use with caution in patients with pre-existing cataracts or ocular trauma or ulceration.

    Accidental exposure

    To avoid accidental exposure and/or ingestion, advise patients to store and dispose of all lidocaine products out of the reach of children and pets. It is important to note that whether new or used, lidocaine patches contain a large amount of lidocaine (at least 665 mg post-use). The potential exists for small children or pets to suffer serious adverse effects from unintended lidocaine exposure including chewing or ingesting a new or used lidocaine patch.

    Intraarterial administration, intrathecal administration, intravenous administration

    When parenteral lidocaine is intended as a local anesthetic, avoid intravenous administration, intraarterial administration, or intrathecal administration. Unintended intravenous or intraarterial administration may result in cardiac arrest and may require prolonged resuscitation. Further, do not administer preservative-containing parenteral lidocaine via intrathecal routes. To avoid intravascular administration of lidocaine during local anesthetic procedures, aspiration should be performed before the local anesthetic is injected and after repositioning of the needle. During epidural administration, a test dose should be administered initially and the patient should be monitored for CNS and cardiovascular toxicity, as well as signs of inadvertent intrathecal administration (see Adverse Reactions). Syringe aspiration should also be performed before and during each supplemental injection in continuous catheter techniques. Clinicians should be aware that the absence of blood return does not guarantee that intravascular injection has been avoided.

    Head and neck anesthesia

    Patients receiving local head and neck anesthesia including retrobulbar, stellate ganglion, and dental blocks, are at increased risk of CNS toxicity similar to the systemic toxicity seen with unintentional intravascular injections of large doses of lidocaine. These reactions may be due to potential intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Patients receiving these blocks should have their ventilatory and circulatory systems monitored closely. Recommended doses should not be exceeded in these patients.

    Ocular surgery

    When local anesthetics, like lidocaine, are used for retrobulbar block during ocular surgery, lack of corneal sensation should not be relied upon to determine whether or not the patient is ready for surgery. Lack of corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.

    Anticoagulant therapy, bleeding, coagulopathy, infection, neurological disease, requires a specialized care setting, requires an experienced clinician, sepsis, spinal anesthesia, thrombocytopenia

    Parenteral use of lidocaine requires an experienced clinician and requires a specialized care setting. Lidocaine preparations containing preservatives should not be used for epidural or spinal anesthesia. Patients with the following conditions should receive spinal anesthesia with caution: pre-existing CNS disorders such as poliomyelitis, pernicious anemia, paralysis from nerve injuries or syphilis;  children < 16 years, or elderly patients; chronic backache; preoperative headache; hypotension; hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients. Consult standard textbooks for specific techniques and precautions for spinal anesthetic procedures. Epidural, local, nerve block and spinal administration of lidocaine are contraindicated in patients with the following: infection or inflammation at the injection site, bacteremia (sepsis), platelet abnormalities, thrombocytopenia less than 100,000/mm3, increased bleeding time, uncontrolled coagulopathy or bleeding, or anticoagulant therapy. Lumbar and caudal epidural anesthesia should be used with extreme caution in patients with existing neurological disease, spinal deformities, sepsis, and severe hypertension. Use caution when applying topical lidocaine to mucous membranes in the presence of sepsis due to the potential for rapid systemic absorption. Patients with platelet disorders or those with bleeding tendencies may be at risk for superficial dermal bleeding when lidocaine is administered intradermally for topical anesthesia.

    Fetal distress, labor, obstetric delivery, pudendal nerve block

    During labor and obstetric delivery, local anesthetics, like lidocaine, can cause varying degrees of maternal, fetal, and neonatal toxicities. The potential for toxicity is related to the procedure performed, the type and amount of drug used, and the technique of administration. Appropriate patient positioning during obstetric delivery may decrease maternal hypotension that can result from regional anesthesia. Injection of the local anesthetic should be performed with the patient in the left lateral decubitus position to displace the gravid uterus, thereby minimizing aortocaval compression. Epidural, spinal, paracervical, or pudendal nerve block may alter the forces of parturition. The use of obstetrical anesthesia may alter the duration of various phases of labor and increase the need for forceps assistance. Electronic fetal monitoring for signs of fetal distress is highly recommended.

    Continuous intraarticular infusion administration

    Lidocaine is not approved for continuous intraarticular infusion administration. Infusion of local anesthetics into a joint space may have caused chondrolysis (see Adverse Reactions). Local anesthetics are not indicated for continuous intraarticular postoperative infusions or for use with infusion devices such as elastomeric pumps.

    Fetal prematurity, paracervical nerve block

    Physicians should weigh the possible risks versus benefits when considering obstetrical paracervical nerve block with parenteral lidocaine in situations of fetal prematurity, toxemia of pregnancy, and fetal distress. Adherence to the recommended dosage is critical during obstetrical paracervical block. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Use of paracervical block in early pregnancy (i.e., anesthesia for elective abortion) may result in rapid systemic absorption and can result in maternal seizures or cardiovascular collapse. The recommended dose of the local anesthetic should not be exceeded. Injections should be administered slowly with frequent aspirations. Allow a 5-minute interval between administration to each side.

    Malignant hyperthermia

    Use lidocaine with caution in patients with a genetic predisposition to malignant hyperthermia. Although it is unknown whether lidocaine triggers this reaction, it is recommended that a standard protocol for management be available when lidocaine is administered in hospital environments.

    Children, infants, neonates, teething pain

    Lidocaine dosages in pediatric patients should be reduced, commensurate with age, body weight and physical condition. When multiple formulations of lidocaine are used at once, the amount systemically absorbed from all formulations must be considered. Resuscitative equipment and facilities should be readily available in case of an emergency when using parenteral products. Repeated doses of parenteral lidocaine may cause a significant increase in blood concentrations with each successive dose; these increases may be poorly tolerated by pediatric patients, particularly by those who are debilitated or the acutely ill. Similar increases in systemic exposure are possible with repeat topical application. Certain products, such as lidocaine transdermal patches, have not been FDA-approved for application to pediatric patients. Non-prescription (OTC) products should not be used without healthcare professional advice in those under 2 years of age, or as directed on the product label. Do not use lidocaine viscous solution for the treatment of teething pain in infants and young children due to the risk of serious adverse reactions, including seizures, cardiopulmonary arrest, severe brain injury, and death. The FDA reviewed 22 cases of serious adverse events that occurred in infants and young children between 5 months and 3.5 years of age after receiving lidocaine viscous solution for the treatment of mouth pain due to teething or stomatitis or who had accidental ingestions. Of the 22 cases, 6 cases resulted in death, 3 were categorized as life-threatening, 11 required hospitalization, and 2 required medical intervention without hospitalization. The FDA recommends against the use of topical pain relievers for teething pain due to the fact that they wash out of the mouth within minutes of application and can cause serious adverse reactions if they are swallowed in excessive amounts. Advise parents and caregivers with teething pain concerns to follow the American Academy of Pediatrics recommendations for the management of teething pain, which include using a teething ring chilled in the refrigerator (not frozen) and gently rubbing or massaging the gums with a finger. For other conditions, the use of viscous lidocaine in neonates, infants, and children 3 years of age and younger should be limited to those situations where safer alternatives are not available or have failed. To ensure safety, doses should be measured by an accurate device, administered no more often than every 3 hours, used only for the prescribed indication, and stored safely out of the reach of children immediately after use. When topical anesthetics are used in the mouth, the topical anesthesia may impair swallowing and thus enhance the danger of aspiration. For this reason, food should not be ingested for 60 minutes following use of local anesthetic preparations in the mouth or throat area. This is particularly important in children because of their frequency of eating.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    arachnoiditis / Early / Incidence not known
    cranial nerve palsies / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    neonatal depression / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    methemoglobinemia / Early / Incidence not known
    chondrolysis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    corneal opacification / Delayed / Incidence not known
    malignant hyperthermia / Rapid / Incidence not known

    Moderate

    erythema / Early / 53.0-67.3
    edema / Delayed / 4.3-8.0
    blurred vision / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    confusion / Early / Incidence not known
    hot flashes / Early / Incidence not known
    euphoria / Early / Incidence not known
    fecal incontinence / Early / Incidence not known
    meningitis / Delayed / Incidence not known
    urinary incontinence / Early / Incidence not known
    neuropathic pain / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    decreased uterine contractility / Early / Incidence not known
    fetal bradycardia / Delayed / Incidence not known
    fetal acidosis / Delayed / Incidence not known
    conjunctival hyperemia / Early / Incidence not known

    Mild

    injection site reaction / Rapid / 0.5-67.3
    petechiae / Delayed / 44.0-46.4
    pruritus / Rapid / 1.0-9.4
    nausea / Early / 2.0-2.0
    vomiting / Early / 1.0-1.0
    dizziness / Early / 0.9-0.9
    tinnitus / Delayed / Incidence not known
    anxiety / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    tremor / Early / Incidence not known
    restlessness / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    headache / Early / Incidence not known
    back pain / Delayed / Incidence not known
    shivering / Rapid / Incidence not known
    weakness / Early / Incidence not known
    skin irritation / Early / Incidence not known
    skin discoloration / Delayed / Incidence not known
    dysesthesia / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    ocular irritation / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Propoxyphene: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Adapalene; Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
    Aldesleukin, IL-2: (Moderate) Concomitant use of systemic lidocaine and aldesleukin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; aldesleukin inhibits CYP3A4.
    Alfentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aliskiren; Amlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Alogliptin; Pioglitazone: (Moderate) Concomitant use of systemic lidocaine and pioglitazone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; pioglitazone induces CYP3A4.
    Ambenonium Chloride: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Amiodarone: (Major) Concomitant administration of lidocaine with amiodarone has been reported to cause sinus bradycardia and seizure. Amiodarone and its main metabolite, N-monodesethylamiodarone (DEA), appear to inhibit the metabolism of lidocaine by competitively inhibiting CYP3A4. Furthermore, DEA inhibits lidocaine metabolism in a concentration-dependent manner. Also, the metabolism of amiodarone to DEA appears to be competitively inhibited by lidocaine. Close correlations between amiodarone N-monodesethylase activities and the amounts of CYP3A4 and the rates of lidocaine N-monodesethylation have been observed from analyses of in vitro data. Inhibition of lidocaine metabolism is supported by in vivo data from 6 adults. The mean systemic concentration of lidocaine over 300 minutes after receipt of lidocaine hydrochloride 1 mg/kg intravenously before amiodarone treatment is 111.7 +/- 23.2 mcg/minute/mL. In contrast, the mean systemic concentration of lidocaine over 300 minutes after cumulative amiodarone doses of 3 g and 13 g is 135.3 +/- 34.6 and 131.7 +/- 25.5 mcg/minute/mL, respectively. As expected, the systemic exposure of the lidocaine metabolite, monoethylglycinexylidide, decreases from 19.2 +/- 6.5 to 15.8 +/- 8.3 mcg/minute/mL after 3 g of amiodarone. In addition, the systemic clearance of lidocaine decreases from 7.86 +/- 1.83 to 6.31 +/- 2.21 mL/minute/kg body weight. As compared with values before amiodarone administration, the lidocaine elimination half-life and the distribution volume at steady state remain relatively unchanged. Due to the long half-life of amiodarone, clinicians should use caution when administering lidocaine to patients who are receiving or who have recently discontinued amiodarone.
    Amitriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Amitriptyline; Chlordiazepoxide: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Amlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Atorvastatin: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Benazepril: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Olmesartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Telmisartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amlodipine; Valsartan: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4.
    Amprenavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Anagrelide: (Moderate) Anagrelide has been shown to inhibit CYP1A2. In theory, coadministration of anagrelide with substrates of CYP1A2, including lidocaine, could lead to increases in the serum concentrations of lidocaine and, thus, adverse effects. Patients receiving anagrelide and lidocaine concomitantly should be monitored for increased toxicity of lidocaine.
    Aprepitant, Fosaprepitant: (Major) Use caution if lidocaine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in lidocaine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. This interaction is not expected with topical preparations of lidocaine. Lidocaine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of systemic lidocaine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Atazanavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Atazanavir; Cobicistat: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of systemic lidocaine with cobicistat. Lidocaine is a substrate for CYP3A4; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated lidocaine plasma concentration.
    Atenolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Atenolol; Chlorthalidone: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Atracurium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Atropine; Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Barbiturates: (Moderate) Lidocaine is a substrate for the cytochrome P450 isoenzymes 1A2 and 3A4. Barbiturates may enhance lidocaine clearance by inducing cytochrome P450 enzymes. In the case of phenobarbital, enhanced lidocaine clearance may persist for several days after phenobarbital is discontinued. Increased lidocaine clearance, however, appears to be of minor clinical significance since IV lidocaine is usually titrated to response.
    Basiliximab: (Moderate) Concomitant use of systemic lidocaine and basiliximab may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; basiliximab may inhibit CYP3A4.
    Belladonna; Opium: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Bendroflumethiazide; Nadolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Benzocaine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
    Benzocaine; Butamben; Tetracaine: (Moderate) Caution is advised if combining topical local anesthetics. The toxic effects of local anesthetics are additive. In addition, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed.
    Benzonatate: (Major) Caution is advised if amide local anesthetics are used concurrently with benzonatate. The toxic effects of local anesthetics are additive.
    Benzoyl Peroxide: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
    Benzoyl Peroxide; Clindamycin: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
    Benzoyl Peroxide; Erythromycin: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
    Benzoyl Peroxide; Sulfur: (Moderate) Concurrent use of benzoyl peroxide and topical anesthetics may decrease the efficacy of the anesthetic. In a clinical study, an estimated 75% increase in patient-reported, prick-induced pain was noted in areas treated with both 5% benzoyl peroxide and 6% benzocaine cream as compared to areas treated with 6% benzocaine cream alone. Investigators attributed the decreased anesthetic effect to a breakdown of the benzocaine molecule by either or both benzoyl peroxide or benzoyl peroxide-derived free radicals. It is recommended that the skin area that is to be topically anesthetized have no previous treatment with benzoyl peroxide or that the skin is thoroughly washed prior to the application of the anesthetic.
    Beta-adrenergic blockers: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Betaxolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Bexarotene: (Moderate) Concomitant use of systemic lidocaine and bexarotene may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; bexarotene induces CYP3A4.
    Bisoprolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Boceprevir: (Major) Close clinical monitoring is advised when administering systemic lidocaine with boceprevir due to an increased potential for serious and/or life-threatening lidocaine-related adverse events. If lidocaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of lidocaine. Lidocaine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated lidocaine plasma concentrations.
    Bosentan: (Moderate) Bosentan is an inducer of CYP3A4 enzymes, and may decrease plasma concentrations of drugs metabolized by these enzymes. Caution is recommended when administering bosentan to patients receiving lidocaine as lidocaine is a CYP3A4 substrate.
    Brigatinib: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration with brigatinib is necessary. Lidocaine is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of lidocaine may decrease.
    Brimonidine; Timolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Capreomycin: (Moderate) Partial neuromuscular blockade has been reported with capreomycin after the administration of large intravenous doses or rapid intravenous infusion. Lidocaine could potentiate the neuromuscular blocking effect of capreomycin by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects.
    Carbamazepine: (Moderate) Concomitant use of systemic lidocaine and carbamazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; carbamazepine induces both hepatic isoenzymes.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Carteolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Carvedilol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Ceritinib: (Moderate) Monitor for lidocaine toxicity if coadministration with ceritinib is necessary. Ceritinib is a CYP3A4 inhibitor; lidocaine is metabolized by CYP3A4 and CYP1A2. Concomitant treatment CYP3A4 inhibitors has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and prolonging the elimination half-life.
    Chloramphenicol: (Moderate) Concomitant use of systemic lidocaine and chloramphenicol may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; chloramphenicol inhibits CYP3A4.
    Chloroprocaine: (Major) Caution is advised if a local anesthetic is used concurrently with other local anesthetics. The toxic effects of the drugs are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage.
    Chloroxylenol; Hydrocortisone; Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
    Chlorpheniramine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cholinesterase inhibitors: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Cimetidine: (Moderate) Concomitant use of systemic lidocaine and cimetidine may increase lidocaine plasma concentrations. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP1A2 and CYP3A4 substrate; cimetidine inhibits both of these isoenzymes. Concomitant use of lidocaine with a weak CYP1A2 and CYP3A4 inhibitor has reportedly increased lidocaine plasma concentrations by 24% to 75%.
    Ciprofloxacin: (Moderate) Concomitant use of systemic lidocaine and ciprofloxacin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ciprofloxacin inhibits both of these isoenzymes. In a study of healthy volunteers (n = 9), concomitant use of lidocaine (1.5mg/kg IV) and ciprofloxacin (500 mg twice daily) resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively.
    Cisatracurium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Citalopram: (Moderate) Concomitant use of systemic lidocaine and citalopram may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; citalopram is a weak CYP1A2 inhibitor.
    Clarithromycin: (Moderate) Concomitant use of systemic lidocaine and clarithromycin may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4.
    Clomipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of systemic lidocaine with cobicistat. Lidocaine is a substrate for CYP3A4; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated lidocaine plasma concentration.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of systemic lidocaine with cobicistat. Lidocaine is a substrate for CYP3A4; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated lidocaine plasma concentration.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of systemic lidocaine with cobicistat. Lidocaine is a substrate for CYP3A4; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated lidocaine plasma concentration.
    Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Guaifenesin: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Phenylephrine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Colesevelam: (Moderate) Colesevelam may decrease the absorption of lidocaine. To minimize potential for interactions, consider administering lidocaine at least 1 hour before or at least 4 hours after colesevelam.
    Conivaptan: (Major) According to the manufacturer, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as lidocaine, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with lidocaine. Treatment with lidocaine may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Crizotinib: (Moderate) Monitor for lidocaine-related adverse reactions and toxicities if coadministration with crizotinib is necessary. Lidocaine is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor.
    Cyclosporine: (Moderate) Concomitant use of systemic lidocaine and cyclosporine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; cyclosporine inhibits CYP3A4.
    Dabrafenib: (Moderate) Concomitant use of systemic lidocaine and dabrafenib may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dabrafenib induces CYP3A4.
    Dalfopristin; Quinupristin: (Moderate) Dalfopristin; quinupristin is a potent inhibitor of cytochrome P450 isoenzyme 3A4, and lidocaine is a substrate for CYP3A4. Concomitant use may cause an increase in lidocaine concentrations, which could increase efficacy or toxicity. If lidocaine and dalfopristin; quinupristin is used concurrently, careful plasma lidocaine concentration monitoring is needed.
    Danazol: (Moderate) Danazol is a CYP3A4 inhibitor and may decrease the hepatic metabolism of lidocaine. Patients receiving lidocaine should be closely monitored for toxicity if danazol is added to therapy.
    Darunavir: (Major) Darunavir can inhibit CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and darunavir should be carefully monitored due to the potential for serious toxicity.
    Darunavir; Cobicistat: (Major) Darunavir can inhibit CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and darunavir should be carefully monitored due to the potential for serious toxicity. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of systemic lidocaine with cobicistat. Lidocaine is a substrate for CYP3A4; cobicistat is an inhibitor of this enzyme. Concurrent use may result in elevated lidocaine plasma concentration.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Dasatinib: (Moderate) Concomitant use of systemic lidocaine and dasatinib may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; dasatinib inhibits CYP3A4.
    Deferasirox: (Major) Concomitant use of systemic lidocaine and deferasirox may alter lidocaine plasma concentrations; avoid concurrent use. If use together is necessary, monitor patients closely for lidocaine toxicity and therapeutic efficacy. Lidocaine is a CYP3A4 and CYP1A2 substrate; deferasirox inhibits CYP1A2 and induces CYP3A4.
    Delavirdine: (Moderate) Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as lidocaine, should be expected with concurrent use of delavirdine.
    Desipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Dexamethasone: (Moderate) Concomitant use of systemic lidocaine and dexamethasone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; dexamethasone induces CYP3A4.
    Dextromethorphan; Quinidine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Dibucaine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Diltiazem: (Moderate) Concomitant use of systemic lidocaine and diltiazem may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; diltiazem inhibits CYP3A4.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Disopyramide: (Major) The effects of concomitant administration of disopyramide with other antiarrhythmics could potentially be synergistic or antagonistic, and adverse cardiac effects could potentially be additive. Class IA antiarrhythmic agents are associated with proarrhythmias (e.g., torsades de pointes) resulting from QTc prolongation. Coadministration of disopyramide with other Class IA antiarrhythmics should be reserved for patients with life-threatening arrhythmias who are unresponsive to single-agent antiarrhythmic therapy. Lidocaine has occasionally been used concurrently with disopyramide; however, additive electrophysiologic effects may occur. Since disopyramide and lidocaine are both sodium-channel-acting agents, it is somewhat irrational to use these drugs together; isolated cases of intraventricular conduction abnormalities have been reported with this drug combination. Patients receiving more than one antiarrhythmic drug must be carefully monitored.
    Disulfiram: (Moderate) Concomitant use of systemic lidocaine and disulfiram may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; disulfiram inhibits CYP1A2.
    Dofetilide: (Severe) Concurrent exposure of systemic lidocaine with dofetilide could increase the risk of dofetilide-induced proarrhythmias. Before switching from lidocaine to dofetilide therapy, lidocaine generally should be withheld for at least three half-lives prior to initiating dofetilide. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).
    Donepezil: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Donepezil; Memantine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Dorzolamide; Timolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Doxacurium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Doxepin: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Dronedarone: (Moderate) Concomitant use of systemic lidocaine and dronedarone may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; dronedarone inhibits CYP3A4.
    Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Efavirenz: (Moderate) Efavirenz induces cytochrome P450 (CYP) 3A4 and thus, may decrease serum concentrations of lidocaine. Caution is recommended when administering efavirenz with CYP3A4 substrates that have a narrow therapeutic range (e.g., systemic lidocaine).
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Efavirenz induces cytochrome P450 (CYP) 3A4 and thus, may decrease serum concentrations of lidocaine. Caution is recommended when administering efavirenz with CYP3A4 substrates that have a narrow therapeutic range (e.g., systemic lidocaine).
    Elbasvir; Grazoprevir: (Moderate) Administering lidocaine with elbasvir; grazoprevir may result in elevated lidocaine plasma concentrations. Lidocaine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Enzalutamide: (Moderate) Coadministration of systemic lidocaine with enzalutamide may decrease lidocaine plasma concentrations; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
    Erythromycin: (Moderate) Erythromycin is a substrate and inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4, and lidocaine is a CYP3A4 substrate. As compared with placebo, receipt of erythromycin 500 mg three times daily for 4 days before intravenous administration of lidocaine 1.5 mg/kg over 60 minutes did not affect the systemic lidocaine concentration. However, the plasma concentration of monoethylglycinexylidide, an active lidocaine metabolite, increased from 56 ng/ml to 80 ng/ml. The clinical significance of this interaction is not known, but the magnitude of effect on lidocaine serum concentrations may be greater when a CYP3A4 inhibitor is coadministered with a CYP1A2 inhibitor. For example, in one study, coadministration of lidocaine with both fluvoxamine (CYP1A2 inhibitor) and erythromycin has been reported to further reduce lidocaine clearance than observed with fluvoxamine alone. Fluvoxamine, a potent CYP1A2 inhibitor, has been shown to reduce lidocaine clearance by approximately 40 to 60% during in vivo studies. However, cytochrome activity was not measured during these trials. Since fluvoxamine has also been reported to moderately inhibit CYP3A4 isoenzymes, CYP3A4 inhibition may have also contributed to the reduction in lidocaine clearance. Until further data are available, it is prudent to monitor for potential lidocaine adverse effects during coadministration of systemic lidocaine and erythromycin and/or fluvoxamine.
    Erythromycin; Sulfisoxazole: (Moderate) Erythromycin is a substrate and inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4, and lidocaine is a CYP3A4 substrate. As compared with placebo, receipt of erythromycin 500 mg three times daily for 4 days before intravenous administration of lidocaine 1.5 mg/kg over 60 minutes did not affect the systemic lidocaine concentration. However, the plasma concentration of monoethylglycinexylidide, an active lidocaine metabolite, increased from 56 ng/ml to 80 ng/ml. The clinical significance of this interaction is not known, but the magnitude of effect on lidocaine serum concentrations may be greater when a CYP3A4 inhibitor is coadministered with a CYP1A2 inhibitor. For example, in one study, coadministration of lidocaine with both fluvoxamine (CYP1A2 inhibitor) and erythromycin has been reported to further reduce lidocaine clearance than observed with fluvoxamine alone. Fluvoxamine, a potent CYP1A2 inhibitor, has been shown to reduce lidocaine clearance by approximately 40 to 60% during in vivo studies. However, cytochrome activity was not measured during these trials. Since fluvoxamine has also been reported to moderately inhibit CYP3A4 isoenzymes, CYP3A4 inhibition may have also contributed to the reduction in lidocaine clearance. Until further data are available, it is prudent to monitor for potential lidocaine adverse effects during coadministration of systemic lidocaine and erythromycin and/or fluvoxamine.
    Eslicarbazepine: (Moderate) Concomitant use of systemic lidocaine and eslicarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; eslicarbazepine induces CYP3A4.
    Esmolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Ester local anesthetics: (Major) Caution is advised if a local anesthetic is used concurrently with other local anesthetics. The toxic effects of the drugs are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage.
    Ethotoin: (Moderate) Lidocaine is a substrate for the cytochrome P450 isoenzymes 1A2 and 3A4. Ethotoin may enhance lidocaine clearance by inducing cytochrome P-450 enzymes.
    Ethyl Chloride: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
    Etravirine: (Major) Etravirine is an inducer of CYP3A4; systemic lidocaine concentrations may be decreased with coadministration. Coadminister these drugs with caution. It is recommended to monitor lidocaine concentrations when possible.
    Famotidine: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
    Famotidine; Ibuprofen: (Moderate) Concomitant use of systemic lidocaine and famotidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; famotidine inhibits CYP1A2.
    Felbamate: (Moderate) Concomitant use of systemic lidocaine and felbamate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; felbamate induces CYP3A4.
    Fentanyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for epidural analgesia or additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Flecainide: (Major) Although causality for torsades de pointes has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation, such as local anesthetics, may have an increased risk of developing proarrhythmias. Use with caution.
    Fluconazole: (Moderate) Concomitant use of systemic lidocaine and fluconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluconazole inhibits CYP3A4.
    Fluoxetine: (Moderate) Concomitant use of systemic lidocaine and fluoxetine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluoxetine inhibits CYP3A4.
    Fluoxetine; Olanzapine: (Moderate) Concomitant use of systemic lidocaine and fluoxetine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; fluoxetine inhibits CYP3A4.
    Fluvoxamine: (Moderate) Concomitant use of systemic lidocaine and fluvoxamine increases lidocaine exposure by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine plasma clearance is decreased by 41% to 60% and the mean half-life prolonged by 1 hour when used in combination with fluvoxamine. Lidocaine is a CYP1A2 and CYP3A4 substrate; fluvoxamine inhibits both of these hepatic isoenzymes.
    Fosamprenavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Fosphenytoin: (Moderate) Lidocaine is a substrate for the cytochrome P450 isoenzymes 1A2 and 3A4. Fosphenytoin may enhance lidocaine clearance by inducing cytochrome P-450 enzymes.
    Furazolidone: (Moderate) Combined hypotensive effects are possible with the combined use of monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine, or isocarboxazid) and spinal anesthetics. If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking MAOIs may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a MAOI or drugs with monoamine oxidase inhibitor activity such as furazolidone should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Galantamine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of antiarrhythmics, however, no clinical data are available.
    Glimepiride; Pioglitazone: (Moderate) Concomitant use of systemic lidocaine and pioglitazone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; pioglitazone induces CYP3A4.
    Guaifenesin; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Homatropine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Ibuprofen: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocortisone; Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
    Hydromorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Ibuprofen; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lidocaine, a CYP3A substrate, as lidocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Imatinib: (Moderate) Imatinib, STI-571 is a potent inhibitor of cytochrome P450 isoenzymes 2C9, 2D6, and 3A4. If concurrent therapy with lidocaine is necessary, caution is warranted and close monitoring of lidocaine plasma concentrations is recommended.
    Imipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Indinavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with lidocaine may result in increased serum concentrations of lidocaine. Lidocaine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isocarboxazid: (Severe) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to etidocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Administration of a phenothiazine or a butyrophenone may reduce or reverse the pressor effect of epinephrine. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    Isoniazid, INH: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4. (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Isoniazid, INH; Rifampin: (Moderate) Concomitant use of systemic lidocaine and isoniazid may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; isoniazid inhibits CYP3A4. (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Itraconazole: (Moderate) Concomitant use of systemic lidocaine and itraconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; itraconazole inhibits CYP3A4.
    Ivacaftor: (Minor) Use caution when administering ivacaftor and lidocaine concurrently. Ivacaftor is an inhibitor of CYP3A and lidocaine is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as lidocaine, can theoretically increase lidocaine exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Ketoconazole: (Moderate) Concomitant use of systemic lidocaine and ketoconazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ketoconazole inhibits CYP3A4.
    Labetalol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Lapatinib: (Major) Concomitant use of systemic lidocaine and lapatinib may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; lapatinib inhibits CYP3A4. Lapatinib can also prolong the QT interval. Lapatinib should be administered with caution to patients who have or may develop prolongation of QTc such as patients taking anti-arrhythmic medicines that lead to QT prolongation.
    Lesinurad: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4.
    Lesinurad; Allopurinol: (Moderate) Concomitant use of systemic lidocaine and lesinurad may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; lesinurad induces CYP3A4.
    Levobetaxolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Levobunolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Levomethadyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Levorphanol: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Lidocaine; Prilocaine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
    Lopinavir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Lumacaftor; Ivacaftor: (Minor) Use caution when administering ivacaftor and lidocaine concurrently. Ivacaftor is an inhibitor of CYP3A and lidocaine is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as lidocaine, can theoretically increase lidocaine exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Magnesium Salts: (Minor) Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
    Meperidine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Meperidine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Metformin; Pioglitazone: (Moderate) Concomitant use of systemic lidocaine and pioglitazone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; pioglitazone induces CYP3A4.
    Methadone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Metoprolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Metyrapone: (Moderate) Concomitant use of systemic lidocaine and metyrapone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; metyrapone induces CYP3A4.
    Mexiletine: (Major) Mexiletine is chemically and pharmacologically similar to lidocaine; cardiac and toxic effects may be additive. In addition, concurrent use may increase plasma lidocaine concentrations due to the displacement of lidocaine from tissue binding sites by mexiletine. If used together, monitor lidocaine plasma concentrations and adjust the dosage as required.
    Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
    Mirabegron: (Moderate) Concomitant use of systemic lidocaine and mirabegron may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; mirabegron inhibits CYP3A4.
    Mitotane: (Major) Use caution if mitotane and lidocaine are used concomitantly, and monitor for decreased efficacy of lidocaine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and lidocaine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of lidocaine.
    Mivacurium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Modafinil: (Moderate) Concomitant use of systemic lidocaine and modafinil may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; modafinil induces both isoenzymes.
    Monoamine oxidase inhibitors: (Severe) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to etidocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Administration of a phenothiazine or a butyrophenone may reduce or reverse the pressor effect of epinephrine. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    Moricizine: (Severe) The effects of concomitant administration of Class IC antiarrhythmic agents with other antiarrhythmics can be synergistic, additive, or antagonistic, and adverse cardiac effects can be additive. Based on Class IC drug pharmacology, moricizine may have additive Class I electrophysiologic effects that can increase the risk for proarrhythmias. Although moricizine primarily is associated with Class IC actions, it also is associated with quinidine-like (i.e, Class IA) features of intermediate effects on sodium channel blockade and lidocaine-like (e.g., Class IB) features of shortening the action potential duration without altering repolarization. In general, combination therapy has been reported to increase the risk of proarrhythmias.
    Morphine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Morphine; Naltrexone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Nadolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Nebivolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Nebivolol; Valsartan: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Nefazodone: (Moderate) Concomitant use of systemic lidocaine and nefazodone may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; nefazodone inhibits CYP3A4.
    Nelfinavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Neostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Netupitant; Palonosetron: (Moderate) Concomitant use of systemic lidocaine and netupitant may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; inhibition of CYP3A4 by netupitant can last for multiple days after a single dose.
    Neuromuscular blockers: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Nevirapine: (Moderate) Nevirapine is an inducer of the cytochrome P4503A enzyme. Concomitant administration of nevirapine with drugs that are extensively metabolized by this enzyme, such as lidocaine, may require dosage adjustments.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval. Systemic lidocaine has been established to have a causal association with QT prolongation and torsade de pointes. Additionally, nilotinib is a moderate CYP3A4 inhibitor and lidocaine is a CYP3A4 substrate; administering these drugs together may result in increased lidocaine levels. If the use of lidocaine is required, hold nilotinib therapy. If the use of nilotinib and lidocaine cannot be avoided, a lidocaine dose reduction may be necessary; close monitoring of the QT interval is recommended.
    Nortriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as lidocaine. Lidocaine is extensively metabolized in the liver into two active compounds, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). The major metabolic pathway, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4. Therapeutic monitoring is recommended with coadministration.
    Octreotide: (Moderate) Concomitant use of systemic lidocaine and octreotide may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; somatostatin analogs decrease growth hormone secretion, which in turn may inhibit 3A4 enzyme function.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Oritavancin: (Moderate) Lidocaine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of lidocaine may be reduced if these drugs are administered concurrently.
    Oxcarbazepine: (Moderate) Concomitant use of systemic lidocaine and oxcarbazepine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; oxcarbazepine induces CYP3A4.
    Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxymorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Palbociclib: (Moderate) Concomitant use of systemic lidocaine and palbociclib may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; palbociclib inhibits CYP3A4.
    Pancuronium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and lidocaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of lidocaine. Use caution when administering these drugs concomitantly.
    Peginterferon Alfa-2b: (Major) Monitor for adverse effects associated with increased exposure to systemic lidocaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while lidocaine is a CYP1A2 substrate.
    Penbutolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Perindopril; Amlodipine: (Moderate) Concomitant use of systemic lidocaine and amlodipine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; amlodipine inhibits CYP3A4.
    Perphenazine; Amitriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Phenelzine: (Severe) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to etidocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Administration of a phenothiazine or a butyrophenone may reduce or reverse the pressor effect of epinephrine. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    Phentermine; Topiramate: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4.
    Phenytoin: (Major) Lidocaine is a substrate for the cytochrome P450 isoenzymes 1A2 and 3A4. Phenytoin may enhance lidocaine clearance by inducing cytochrome P-450 enzymes. Additive cardiac depression is possible when phenytoin is administered with lidocaine. Phenytoin injection contains 40% propylene glycol. Too rapid IV administration of phenytoin can produce cardiac arrhythmias, hypotension, and/or death.
    Physostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Pindolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Pioglitazone: (Moderate) Concomitant use of systemic lidocaine and pioglitazone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; pioglitazone induces CYP3A4.
    Polymyxins: (Moderate) Lidocaine can potentiate the neuromuscular blocking effect of colistimethate sodium by impairing transmission of impulses at the motor nerve terminals. If these drugs are used in combination, monitor patients for increased adverse effects. Neuromuscular blockade may be associated with colistimethate sodium, and is more likely to occur in patients with renal dysfunction.
    Posaconazole: (Major) Posaconazole and lidocaine should be coadministered with caution due to an increased potential for lidocaine-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used in combination may result in elevated lidocaine plasma concentrations, causing an increased risk for lidocaine-related adverse events.
    Pramoxine: (Moderate) Caution is advised if combining local anesthetics. The toxic effects of local anesthetics are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage. In addition to additive toxic effects, rare and sometimes fatal cases of methemoglobinemia have been reported with the use of topical or oromucosal benzocaine-containing products. Clinicians should closely monitor patients for the development of methemoglobinemia when a combination local anesthetic is used during a procedure. If a patient becomes cyanotic or if elevated methemoglobin concentrations are suspected, immediately institute treatment to counteract methemoglobinemia (such as administration of methylene blue) as oxygen delivery is ineffective throughout the body until the condition is reversed. Patients who are receiving other drugs that can cause methemoglobin formation, such as prilocaine, are at greater risk for developing methemoglobinemia.
    Procainamide: (Major) Concurrent use of systemic lidocaine and other antiarrhythmic drugs such as procainamide may result in additive or antagonistic cardiac effects and additive toxicity. Patients receiving more than one antiarrhythmic drug must be carefully monitored; dosage reduction may be necessary.
    Procaine: (Major) Caution is advised if a local anesthetic is used concurrently with other local anesthetics. The toxic effects of the drugs are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage.
    Procarbazine: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Propafenone: (Major) There is limited experience with the use of propafenone with Class IB antiarrhythmics. No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, the concomitant use of propafenone and lidocaine has been reported to increase the risks of central nervous system side effects of lidocaine. When propafenone is coadministered, the dose of lidocaine should be titrated to the desired therapeutic effects.
    Propofol: (Moderate) Concomitant use of systemic lidocaine and propofol may increase lidocaine plasma concentrations by reducing lidocaine clearance. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 substrate and propofol is a CYP3A4 inhibitor.
    Propoxyphene: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Propranolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Protriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Pyridostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Quinidine: (Major) Avoid concurrent use of quinidine with other antiarrhythmics with Class I activities, such as lidocaine. Concurrent use may result in additive or antagonistic cardiac effects and additive toxicity.
    Quinine: (Moderate) Concomitant use of systemic lidocaine and quinine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; quinine inhibits CYP3A4.
    Ranolazine: (Major) Ranolazine is an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A, and lidocaine is a substrate for this pathway. Thus, ranolazine may theoretically reduce lidocaine clearance. If concurrent therapy with ranolazine is necessary, administer lidocaine parenteral infusions with caution and monitor lidocaine serum concentrations.
    Rapacuronium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Remifentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Ribociclib: (Moderate) Use caution if ribociclib is coadministered with lidocaine, as the systemic exposure of lidocaine may increase resulting in lidocaine-related adverse reactions. Adjust the dose of lidocaine if necessary. Ribociclib is a moderate CYP3A4 inhibitor and lidocaine is a CYP3A4 substrate.
    Ribociclib; Letrozole: (Moderate) Use caution if ribociclib is coadministered with lidocaine, as the systemic exposure of lidocaine may increase resulting in lidocaine-related adverse reactions. Adjust the dose of lidocaine if necessary. Ribociclib is a moderate CYP3A4 inhibitor and lidocaine is a CYP3A4 substrate.
    Rifabutin: (Moderate) Concomitant use of systemic lidocaine and rifabutin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; rifabutin induces CYP3A4.
    Rifampin: (Moderate) Rifampin is a potent inducer of the cytochrome P-450 hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of lidocaine,
    Rifapentine: (Moderate) Concomitant use of systemic lidocaine and rifapentine may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; rifapentine induces CYP3A4.
    Ritonavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Rituximab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Rivastigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Rocuronium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Saquinavir: (Severe) The concurrent use of systemic lidocaine and saquinavir boosted with ritonavir is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of lidocaine. These drugs used together may result in large increases in lidocaine serum concentrations, which could cause fatal cardiac arrhythmias. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as lidocaine.
    Selegiline: (Severe) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to etidocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Administration of a phenothiazine or a butyrophenone may reduce or reverse the pressor effect of epinephrine. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    Simeprevir: (Moderate) Simeprevir, a mild CYP1A2 inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of lidocaine, which is a CYP1A2 and CYP3A4 substrate. Monitor patients for adverse effects of lidocaine, such as CNS and cardiovascular effects.
    St. John's Wort, Hypericum perforatum: (Moderate) Concomitant use of systemic lidocaine and St. John's Wort may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; St. John's Wort induces CYP3A4.
    Streptogramins: (Moderate) Dalfopristin; quinupristin is a potent inhibitor of cytochrome P450 isoenzyme 3A4, and lidocaine is a substrate for CYP3A4. Concomitant use may cause an increase in lidocaine concentrations, which could increase efficacy or toxicity. If lidocaine and dalfopristin; quinupristin is used concurrently, careful plasma lidocaine concentration monitoring is needed.
    Succinylcholine: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Sufentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tacrine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used; dosage adjustments of the cholinesterase inhibitor may be necessary. In addition, inhibitors of CYP1A2, such as tacrine, could theoretically reduce lidocaine metabolism and increase the risk of toxicity when given concurrently. Also, rivastigmine is an acetylcholinesterase inhibitor and therefore is likely to exaggerate muscle relaxation under general anesthetics.
    Tamoxifen: (Moderate) Concomitant use of systemic lidocaine and tamoxifen may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; tamoxifen inhibits CYP3A4.
    Telaprevir: (Major) Close clinical monitoring is advised when administering systemic lidocaine with telaprevir due to an increased potential for serious and/or life-threatening lidocaine-related adverse events. If lidocaine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on metabolic pathways. Lidocaine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated lidocaine plasma concentrations.
    Telithromycin: (Moderate) Telithromycin, a ketolide antibiotic, can compete with lidocaine for metabolism by CYP3A4. This can result in increased systemic concentrations of lidocaine if the two drugs are coadministered.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and lidocaine is necessary, as the systemic exposure of lidocaine may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of lidocaine; consider increasing the dose of lidocaine if necessary. Lidocaine is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Teriflunomide: (Moderate) As teriflunomide is a weak inducer of CYP1A2, exposure to lidocaine, a CYP1A2 substrate, may be reduced. Caution should be exercised with concurrent use. Patients should be monitored for loss of antiarrhythmic effect if teriflunomide therapy is initiated. Conversely, lidocaine doses may need adjustment if teriflunomide treatment is discontinued.
    Tetracaine: (Major) Caution is advised if a local anesthetic is used concurrently with other local anesthetics. The toxic effects of the drugs are additive. A major cause of adverse reactions appears to be excessive plasma concentrations, which may be due to accidental intravascular administration, slow metabolic degradation, or overdosage.
    Thiabendazole: (Moderate) Concomitant use of systemic lidocaine and thiabendazole may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; thiabendazole is a potent CYP1A2 inhibitor.
    Ticagrelor: (Moderate) Concomitant use of systemic lidocaine and ticagrelor may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticagrelor inhibits CYP3A4.
    Ticlopidine: (Moderate) Concomitant use of systemic lidocaine and ticlopidine may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; ticlopidine inhibits CYP1A2.
    Timolol: (Major) Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction. This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
    Tipranavir: (Moderate) Anti-retroviral protease inhibitors can inhibit hepatic cytochrome P450 3A4, an isoenzyme that is partially responsible for the metabolism of lidocaine. The concurrent use of systemic lidocaine and anti-retroviral protease inhibitors should be carefully monitored due to the potential for serious toxicity.
    Tocainide: (Major) Because tocainide is a lidocaine analog, it would be illogical to administer class 1B antiarrhythmic agents simultaneously unless a patient needs to be converted from parenteral lidocaine therapy to oral tocainide therapy. Additive CNS toxicity can occur during concurrent tocainide and lidocaine therapy.
    Topiramate: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4.
    Trandolapril; Verapamil: (Moderate) Concomitant use of systemic lidocaine and verapamil may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; verapamil inhibits both hepatic isoenzymes.
    Tranylcypromine: (Severe) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to etidocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Administration of a phenothiazine or a butyrophenone may reduce or reverse the pressor effect of epinephrine. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    Tricyclic antidepressants: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Trimipramine: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthesia, receipt of the product to a patient taking tricyclic antidepressants (TCA) may lead to severe, prolonged hypertension. In general, concurrent use of a local anesthetic solution containing epinephrine and a TCA should be avoided. If coadministration is necessary, careful patient monitoring is essential.
    Tubocurarine: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Vancomycin: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Vecuronium: (Moderate) Local anesthetics can prolong and enhance the effects of neuromuscular blockers. Monitoring of neuromuscular function is recommended.
    Verapamil: (Moderate) Concomitant use of systemic lidocaine and verapamil may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; verapamil inhibits both hepatic isoenzymes.
    Voriconazole: (Moderate) Voriconazole is an inhibitor of cytochrome P450 isoenzyme 3A4, and lidocaine is a substrate for the cytochrome P450 isoenzyme 3A4. Thus, voriconazole may theoretically reduce lidocaine clearance. If concurrent therapy with lidocaine is necessary, caution is warranted and close monitoring of lidocaine plasma concentrations is recommended.
    Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as lidocaine.
    Zileuton: (Minor) Concomitant use of systemic lidocaine and zileuton may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; in vitro data indicates zileuton is both a substrate and inhibitor of CYP1A2.

    PREGNANCY AND LACTATION

    Pregnancy

    Lidocaine is classified as FDA pregnancy category B. Reproductive studies conducted in rats have not demonstrated lidocaine-induced fetal harm; however, animal studies are not always predictive of human response. There are no adequate or well controlled studies of lidocaine in pregnant women. Local anesthetics are known to cross the placenta rapidly and, when administered for epidural, paracervical, pudendal, or caudal block anesthesia, and to cause fetal toxicity. The frequency and extent of toxicity are dependent on the procedure performed. Maternal hypotension can result from regional anesthesia, and elevating the feet and positioning the patient on her left side may alleviate this effect. Topical ocular application of lidocaine is not expected to result in systemic exposure. When lidocaine is used for dental anesthesia, no fetal harm has been observed; lidocaine is generally the dental anesthetic of choice during pregnancy and guidelines suggest the second trimester is the best time for dental procedures if they are necessary. A study by the American Dental Association provides some evidence that, when needed, the use of dental local or topical anesthetics at 13 weeks to 21 weeks of pregnancy or later is likely safe and does not raise incidences of adverse pregnancy outcomes or other adverse events; the study analyzed data from the Obstetrics and Periodontal Therapy (OPT) trial, a multicenter study of over 800 pregnant patients in the early to mid second trimester who received required dental procedures.

    MECHANISM OF ACTION

    Mechanism of Action: Lidocaine's antiarrhythmic effects result from its ability to inhibit the influx of sodium through the "fast" channels of the myocardial cell membrane, thereby increasing the recovery period after repolarization. Lidocaine suppresses automaticity and decreases the effective refractory period and the action potential duration in the His-Purkinje system at concentrations that do not suppress automaticity at the SA node. The drug suppresses spontaneous depolarizations in the ventricles by inhibiting reentry mechanisms, and it appears to act preferentially on ischemic tissue. Lidocaine shortens the refractory period, unlike procainamide, which lengthens it. Also, lidocaine does not possess vagolytic properties.Lidocaine produces its analgesics effects through a reversible nerve conduction blockade by diminishing nerve membrane permeability to sodium, just as it affects sodium permeability in myocardial cells. This action decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, skeletal muscle tone. Direct nerve membrane penetration is necessary for effective anesthesia, which is achieved by applying the anesthetic topically or injecting it subcutaneously, intradermally, or submucosally around the nerve trunks or ganglia supplying the area to be anesthetized.

    PHARMACOKINETICS

    Lidocaine is administered dermally, topically, ophthalmically, and parenterally. It is extensively metabolized in the liver into two active compounds, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), which possess 100% and 25% of the potency of lidocaine, respectively. The major metabolic pathway, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4. After intravenous administration, MEGX and GX concentrations in serum range from 11—36% and from 5—11%, respectively, of lidocaine concentrations. Serum concentrations of MEGX were about one-third the serum lidocaine concentrations. It is not known if lidocaine is metabolized in the skin. The initial half-life in an otherwise healthy individual is 7—30 minutes, followed by a terminal half-life of 1.5—2 hours. The half-life of MEGX is 0.5—3.3 hours. Lidocaine and its metabolites are excreted by the kidneys. More than 98% of an absorbed dose can be recovered in the urine as metabolites or parent drug. Less than 10% is excreted unchanged in adults.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP3A4
    Lidocaine is extensively metabolized in the liver into two active compounds, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). The major metabolic pathway, sequential N-deethylation to MEGX and GX, is primarily mediated by CYP1A2 with a minor role of CYP3A4.

    Oral Route

    If swallowed, lidocaine is nearly completely absorbed, but it undergoes extensive first-pass metabolism in the liver, resulting in a systemic bioavailability of only 35%. Although it is not administered orally, some systemic absorption is possible when using oral viscous solutions.

    Intravenous Route

    After intravenous injection, lidocaine distributes in two phases. The early phase represents distribution into the most highly perfused tissues. During the second, slower phase, the drug distributes into adipose and skeletal muscle tissues. Distribution can be decreased in patients with heart failure. In healthy patients, the steady-state volume of distribution is approximately 0.8—1.3 L/kg. The onset of action of intravenous doses is immediate. The duration of action is 10—20 minutes with an intravenous dose, although this is highly dependent on hepatic function.

    Intramuscular Route

    The onset of action of an intramuscularly administered dose is 5—15 minutes. The duration of action is 60—90 minutes with an intramuscular dose, although this is highly dependent on hepatic function.

    Subcutaneous Route

    Only minimal amounts of lidocaine enter the circulation after subcutaneous injection, but repeated dosing may result in detectable lidocaine blood concentrations due to gradual accumulation of the drug or its metabolites. The duration of action of subcutaneously administered lidocaine is 1—3 hours, depending upon the strength of the preparation used. The addition of epinephrine 1:200,000 to 1:100,000 slows the vascular absorption of lidocaine and prolongs its effects.

    Topical Route

    Transdermal absorption of lidocaine is related to the duration of application and the surface area over which the patch is applied. When the dermal patch (Lidoderm) is used as directed, only 3 +/- 2% of the dose applied is expected to be absorbed transcutaneously with very little systemic absorption. After application of patches over a 420 cm2 area of intact skin for 12 hours, the absorbed dose of lidocaine was 64 mg resulting in a Cmax of 0.13 mcg/ml. The lidocaine concentration does not increase with daily use in patients with normal renal function. After topical administration of viscous solutions or jelly to mucous membranes, the duration of action is 30—60 minutes with peak effects occurring within 2—5 minutes.
     
    Local anesthesia starts to occur within 2.5 minutes of application of the DentiPatch to intact mucous membranes. During 15 minutes of system application, serum concentrations of lidocaine are < 0.1 mcg/ml. After removal of the patch after 15 minutes of application, local anesthesia continues for approximately 30—40 minutes. The maximum plasma concentration after the application of the Dentipatch is approximately one-seventh of the concentration achieved by the application of 5% lidocaine ointment.
     
    Administration of lidocaine into the dermis with Zingo yields local dermal analgesia within 1—3 minutes of application. Analgesia diminishes within 10 minutes of administration. In adults, lidocaine plasma concentrations were undetectable (< 5 ng/ml) after a single dose of Zingo.

    Other Route(s)

    Ocular Route
    Administration of lidocaine on the ocular surface with Akten yields ocular anesthesia within 20 seconds to 5 minutes of application. Generally, anesthesia occurs within the first 60 seconds of application. The duration of anesthesia ranges from 5—30 minutes with a mean duration of 15 minutes.