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Xylocaine
Classes
Amide Local Anesthetics
Anti-arrhythmics, Class I-B
Miscellaneous Topical Agents for Local Pain
Ophthalmological Local Anaesthetics
Other Agents for Local Oral Treatment
Topical Anti-hemorrhoidals
Topical Local Anesthetics
Topical Neuropathic Pain agents
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.
Monitor blood pressure and ECG during IV administration.
IV Push
During cardiopulmonary resuscitation (CPR): Administer IV push.
Non-CPR indications: Administer bolus injection at a rate of 0.35 to 0.7 mg/kg/minute (25 to 50 mg/minute).
Continuous IV Infusion
Add 1 or 2 g 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.
ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 8 mg/mL.[64020]
ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 4 mg/mL or 8 mg/mL.
Use an infusion pump to administer by continuous infusion.
Inject, preferably, deep into the deltoid muscle. The quadriceps muscle has also been used for injection.
Intramuscular administration should not be used in the presence of shock due to potential unreliable systemic absorption.
Intradermal Administration (Zingo)
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 Administration
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 unsuccessful or not feasible.[43713] [60636]
Dental, Peripheral, or Sympathetic Block
Consult specialized references for proper injection technique.
Inject slowly and with frequent aspirations to prevent intravascular 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.
Have resuscitative equipment and drugs for the management of adverse reactions immediately available while administering local anesthetics to mucous membranes.
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.
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.
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 Topical System (ZTlido)
Keep the system in the sealed envelope until immediately before use.
Systems may be cut into smaller sizes prior to removal of the release liner.
After removing the system from the protective envelope, immediately apply to intact skin to cover the most painful area. Do not expose the eyes.
Adherence of the system may be affected by contact with water; advise patients that the system may be briefly exposed to water (such as showering for 10 minutes or immersion for 15 minutes). Dry the system after water exposure by gently patting the skin.
Do not apply external heat sources, including heating pads and electric blankets, directly to the system. The system can be applied to the administration site after moderate heat exposure (e.g., 15 minutes of heating pad exposure on a medium setting). The system may be used during moderate exercise (e.g., biking for 30 minutes).
If a system comes off completely and will not stick to the skin, it should be thrown away and a new system should be applied for a total duration of 12 hours of new and previous topical systems together.
Wash hands immediately after handling the system. To discard, fold the system so that the adhesive side sticks to itself. Safely dispose used systems where children or pets cannot get to them.
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.
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.
Single-use Foam Applicator
Apply using gloved hands.
Swirl the applicator tip prior to removing the swab from the pouch.
Apply to the area 3 to 5 minutes prior to the procedure not more than 4 times daily.
Do not use in large quantities over raw or blistered skin.
For ophthalmic administration under the direct supervision of a health care provider. The product is NOT intended for patient self-administration.
Do not touch the tip of the tube to the eye, fingertips, or other surface.
Endotracheal Administration
NOTE: Lidocaine is not FDA-approved for endotracheal (ET) administration.
Consider ET administration only when other access is not available. ET administration is the least-preferred administration due to its association with unpredictable (but generally low) drug concentrations and lower rates of ROSC and survival.
If CPR is in progress, stop chest compressions briefly and administer the medication.
Adults: Dilute the dose in 5 to 10 mL of saline or sterile water. Studies suggest dilution with sterile water may achieve better drug absorption compared to saline.
Pediatrics: Dilute the dose in 1 to 5 mL of saline or follow drug administration with a saline flush (5 mL or more) and 5 consecutive positive-pressure ventilations.
Adverse Reactions
respiratory arrest / Rapid / Incidence not known
seizures / Delayed / Incidence not known
arachnoiditis / Early / Incidence not known
cranial nerve palsies / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
bradycardia / Rapid / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
neonatal depression / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
laryngospasm / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
bronchospasm / 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
erythema / Early / 53.0-67.3
edema / Delayed / 4.3-8.0
euphoria / Early / Incidence not known
hyperesthesia / Delayed / Incidence not known
respiratory depression / Rapid / Incidence not known
confusion / Early / Incidence not known
hot flashes / Early / Incidence not known
blurred vision / 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
skin erosion / Delayed / Incidence not known
dyspnea / Early / Incidence not known
conjunctival hyperemia / Early / Incidence not known
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
agitation / Early / Incidence not known
hypoesthesia / Delayed / Incidence not known
dysarthria / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
asthenia / Delayed / Incidence not known
drowsiness / Early / Incidence not known
tremor / Early / Incidence not known
tinnitus / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
restlessness / Early / Incidence not known
metallic taste / 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
flushing / Rapid / Incidence not known
ecchymosis / Delayed / Incidence not known
skin irritation / Early / Incidence not known
dysesthesia / Delayed / Incidence not known
skin discoloration / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
ocular irritation / Rapid / Incidence not known
Boxed Warning
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.
Common Brand Names
7T Lido, Akten, ALOCANE, ANASTIA, AneCream, Anestacon, Aspercreme with Lidocaine, Astero, BenGay, Blue Tube, Blue-Emu, CidalEaze, DermacinRx Lidogel, DermacinRx Lidorex, DERMALID, GEN7T, Glydo, Gold Bond, LidaMantle, LIDO-K, LIDO-SORB, Lidocan, Lidocare, Lidoderm, LidoDose, LidoDose Pediatric, Lidofore, LidoHeal-90, Lidomar, Lidomark, LidoReal-30, LidoRx, Lidosense 4, Lidosol, Lidosol-50, Lidotral, Lidovix L, LIDOZION, Lidozo, LMX 4, LMX 4 with Tegaderm, LMX 5, Lydexa, MENTHO-CAINE, Moxicaine, Numbonex, Professional DNA Collection Kit, ReadySharp Lidocaine, RectaSmoothe, RectiCare, Salonpas Lidocaine, Senatec, SOLUPAK, SUN BURNT PLUS, Tranzarel, VacuStim Silver, Xyliderm, Xylocaine, Xylocaine MPF, Xylocaine Topical Jelly, Xylocaine Topical Solution, Xylocaine Viscous, Zilactin-L, Zingo, Zionodi, ZTlido
Dea Class
OTC, Rx
Description
Amide local anesthetic and type IB antiarrhythmic
Used IV for acute, life-threatening ventricular arrhythmias; topically and locally for anesthesia
Continuous ECG monitoring necessary when given IV
Dosage And Indications
NOTE: See resuscitation indication for dosage guidelines for VF or pulseless VT (pVT).
Intravenous dosage Adults
1 to 1.5 mg/kg/dose IV load then 1 to 4 mg/minute (0.02 to 0.05 mg/kg/minute in the average 70 kg adult) IV infusion. Administer with constant ECG monitoring. Terminate IV infusion as soon as the cardiac rhythm stabilizes or if toxicity occurs. It is rarely necessary to continue IV infusions for more than 24 hours. Due to reduced clearance of lidocaine after prolonged infusions, a 50% reduction in the infusion rate may be necessary to avoid toxicity if therapy more than 24 hours is required. When feasible, switch to an oral antiarrhythmic agent for maintenance therapy.[32857]
1 mg/kg (Max: 100 mg) IV load then 20 to 50 mcg/kg/minute IV. May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max IV load: 3 mg/kg or 300 mg, whichever is less, administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute IV has been recommended in patients with shock, heart failure, or cardiac arrest. Monitor blood pressure and the electrocardiogram (ECG) during IV lidocaine administration. Terminate IV infusion as soon as the cardiac rhythm stabilizes or if toxicity occurs. It is rarely necessary to continue IV infusions for longer than 24 hours. Due to reduced clearance of lidocaine after prolonged infusions, a 50% reduction in the infusion rate is necessary to avoid toxicity if therapy longer than 24 hours is required. When feasible, switch to an oral antiarrhythmic agent for maintenance therapy.
1 mg/kg IV load then 20 to 50 mcg/kg/minute IV. May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max IV load: 3 mg/kg administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute IV has been recommended in patients with shock, heart failure, or cardiac arrest. Monitor blood pressure and the electrocardiogram (ECG) during IV lidocaine administration. Terminate IV infusion as soon as the cardiac rhythm stabilizes or if toxicity occurs. It is rarely necessary to continue IV infusions for longer than 24 hours. Due to reduced clearance of lidocaine after prolonged infusions, a 50% reduction in the infusion rate is necessary to avoid toxicity if therapy longer than 24 hours is required. When feasible, switch to an oral antiarrhythmic agent for maintenance therapy.
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.
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.
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.
Spray the pharynx with 1 to 5 mL (40 to 200 mg or 0.6 to 3 mg/kg).
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.
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.
Apply 2 to 2.5 g for 20 to 60 minutes before procedure and cover with an occlusive dressing (Max application time: 2 hours).
Apply 1 g for 20 to 40 minutes before procedure and cover with an occlusive dressing (Max application time: 1 hour).
Apply to area 3 to 5 minutes prior to procedure not more than 4 times daily.
Apply to area 3 to 5 minutes prior to procedure not more than 4 times daily.
Apply a thin layer of gel to the wound surface and the immediate surrounding skin 3 to 4 times daily.
Apply a thin layer of gel to the wound surface and the immediate surrounding skin 3 to 4 times daily.
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).
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.
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.
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).
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.
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 1 to 4 pumps of gel to the affected area 3 to 4 times daily (Max: 16 pumps from the airless pump bottle/day; 1 pump covers an area 2 by 2 inches); do not exceed 120 mg of lidocaine per day. For lidocaine 2.75% and 3% lotion, apply a thin film to the affected area 2 to 3 times daily.
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 1 to 4 pumps of gel to the affected area 3 to 4 times daily (Max: 16 pumps from the airless pump bottle/day; 1 pump covers an area 2 by 2 inches); do not exceed 120 mg of lidocaine per day. For lidocaine 2.75% and 3% lotion, apply a thin film to the affected area 2 to 3 times daily.
Apply to intact skin of the affected area up to 4 times daily.
Apply to intact skin of the affected area up to 4 times daily.
Apply to affected area up to 6 times per day.
Apply to affected area up to 6 times per day.
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.
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.
Clean the burn area with mild soap and water. Apply the pad over the burn or wound and cover with adhesive tape or gauze. Avoid application of large quantities, especially over raw or blistered areas.
Clean the burn area with mild soap and water. Apply the pad over the burn or wound and cover with adhesive tape or gauze. Avoid application of large quantities, especially over raw or blistered areas.
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).
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.
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.
Apply patch to affected area every 8 to 12 hours. Leave patch in place for up to 8 but no more than 12 hours.
Apply patch to affected area every 8 to 12 hours. Leave patch in place for up to 8 but no more than 12 hours.
NOTE: Lidocaine dermal patch has been designated an orphan drug by the FDA for this indication.
NOTE: 1 Lidoderm (lidocaine patch 5%) provides equivalent lidocaine exposure to 1 ZTlido (lidocaine topical system 1.8%).
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.
NOTE: 1 ZTlido (lidocaine topical system 1.8%) provides equivalent lidocaine exposure to 1 Lidoderm (lidocaine patch 5%).
Apply up to 3 topical systems to intact skin to cover the most painful area for up to 12 hours in a 24-hour period. Smaller areas of treatment are recommended in debilitated patients or patients with impaired elimination. The system may be cut into smaller sizes prior to removal of the release liner.
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 retrobulbar injection the dose is 3 to 5 mL (120 to 200 mg or 1.7 to 3 mg/kg). A portion of this dose is injected retrobulbarly and the rest may be used to block the facial nerve.
2 drops applied to the ocular surface in the area of the planned procedure. Additional doses may be used to maintain anesthesia. Administer under the direct supervision of a health care provider.
2 drops applied to the ocular surface in the area of the planned procedure. Additional doses may be used to maintain anesthesia. Administer under the direct supervision of a health care provider.
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 to 100 mg (1 to 5 mL of a 2% solution).
5 to 300 mg (up to 60 mL of 0.5% solution or 30 mL of a 1% solution) for percutaneous anesthesia. 50 to 300 mg (10 to 60 mL of 0.5% solution) for intravenous regional infiltration anesthesia.
50 to 300 mg (10 to 60 mL of a 0.5% solution) IV.
100 mg (10 mL of a 1% solution) per side.
30 to 50 mg (3 to 5 mL of a 1% solution).
30 mg (3 mL of a 1% solution).
225 to 300 mg (15 to 20 mL of a 1.5% solution).
200 mg total dose. One-half of the total dose is administered to each side. Inject slowly, five minutes between sides.
0.4 to 1 mL of 1% lidocaine given subcutaneously as 2 injections into the base of the penis 3 to 8 minutes prior to the procedure.
50 mg (5 mL of a 1% solution).
50 to 100 mg (5 to 10 mL of a 1% solution).
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.
250 to 300 mg (25 to 30 mL of a 1% solution).
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.
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.
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 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.
1.5 to 2 mL (75 to 100 mg) of 5% solution.
1 to 1.5 mg/kg IV or IO bolus, followed by 1 to 4 mg/minute (30 to 50 mcg/kg/minute) continuous IV infusion. May administer additional doses of 0.5 to 0.75 mg/kg IV/IO every 5 to 10 minutes as needed. Max cumulative load: 3 mg/kg.[45649] [63999] Use lower infusion rates for patients who are elderly, have heart failure or hepatic disease, or are debilitated.[45773] Guidelines recommend lidocaine for ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) that is unresponsive to CPR, defibrillation, and a vasopressor. Evidence is inadequate regarding the routine use of lidocaine after cardiac arrest or early (within the first hour) after return of spontaneous circulation (ROSC). However, prophylactic use of lidocaine may be considered in certain circumstances (e.g., during emergency medical services transport) when treatment of recurrent VF/pVT may be challenging.[63999]
1 mg/kg IV or IO bolus, followed by 20 to 50 mcg/kg/minute continuous IV infusion.[43713] May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max load: 3 mg/kg or 300 mg, whichever is less, administered over a 1-hour period. A maximum infusion rate of 20 mcg/kg/minute has been recommended in patients with shock, heart failure, or cardiac arrest.[53638] Either lidocaine or amiodarone can be used for shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT).[64000] 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 PALS algorithm to prevent arrhythmias secondary to myocardial infarction in patients with cocaine overdose.[43713]
1 mg/kg IV or IO bolus, followed by 20 to 50 mcg/kg/minute continuous IV infusion.[43713] May repeat bolus if the infusion is initiated more than 15 minutes after the initial bolus. Max load: 3 mg/kg administered over a 1-hour period.[64934] A maximum infusion rate of 20 mcg/kg/minute has been recommended in patients with shock, heart failure, or cardiac arrest.[53638] Either lidocaine or amiodarone can be used for shock-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT).[64000] 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.
NOTE: Consider ET administration only when other access is not available. ET administration is the least-preferred administration due to its association with unpredictable (but generally low) drug concentrations and lower rates of ROSC and survival.
2 to 4 mg/kg/dose via ET tube.
2 to 3 mg/kg/dose via ET tube.
2 to 3 mg/kg/dose via ET tube.
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).
1 to 3 mg/kg IV given 30 seconds to 5 minutes prior to laryngoscopy has been recommended as an optional adjunct for rapid sequence intubation (RSI) in patients with increased intracranial pressure. Maximum efficacy occurs 3 to 5 minutes after injection. When a neuroprotective agent (e.g., etomidate) is used for RSI, lidocaine is not likely to provide additional benefit.[44771]
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 more than 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 significantly lower in the intratracheal group compared to the IV group.
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 intratracheal lidocaine reduced the baseline ICP; however, both treatments suppressed an acute rise in ICP during suctioning. The mean peak ICP after suctioning was significantly lower in the intratracheal group compared to the IV group.
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.
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.
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).
1 to 2 mg/kg IV loading dose over 10 minutes followed by a continuous infusion of 2 to 6 mg/kg/hour IV has been reported. The mean duration of infusion in various studies ranged from 14.6 to 105.7 hours.
2 mg/kg IV loading dose over 10 minutes followed by an infusion of 6 mg/kg/hour IV for 6 hours, then 4 mg/kg/hour IV for 12 hours, then 2 mg/kg/hour IV for 12 hours has been recommended as a second- or third-line treatment. Regimens utilizing a short duration of infusion are recommended in order to reduce accumulation of lidocaine and its metabolites and reduce toxicity. If seizures persist during treatment, this may be a sign of accumulation and dose reduction may be necessary. This regimen was effective in 78% of the treatment courses in a small study (n = 15). Although premature neonates were included in this study (n = 4, gestational age 27 to 33 weeks), these patients experienced higher plasma lidocaine concentrations compared to term neonates.[53516] [53801] An initial infusion rate of 4 mg/kg/hour IV for 24 hours then tapered by 1 mg/kg/hour IV every 24 hours for 4 days was used in a small study of premature (n = 5, gestational age 29 to 35 weeks) and term neonates (n = 8). This regimen was effective in 85% of the patients. However, due to reduced clearance seen in premature neonates compared to term neonates, lower initial doses may be warranted in this population.[53805]
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.
Initially, 1 patch for smaller patients (25 to 27 kg) and 2 patches for larger patients (40 to 56 kg) applied for 12 hours in a 24 hour period was used in a small case series (n = 5, age 11 to 18 years) of patients with neuropathic pain secondary to surgery. Pain control was achieved in 4 out of the 5 patients. Apply patches to intact skin to cover the most painful area. Patches may be cut into smaller sizes with scissors prior to removal of the release liner.
100 to 300 mg (5 to 15 mL) PO as a single dose in combination with an oral liquid antacid and with or without an oral liquid anticholinergic.
†Indicates off-label use
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; however, dosage adjustment may be required. Administer IV lidocaine at a lower maintenance infusion rate and monitor for toxicity. Hepatic dysfunction may decrease the clearance and increase the exposure of lidocaine.
Renal ImpairmentSpecific guidelines for dosage adjustments in renal impairment are not available; however, dosage adjustment may be required. Administer IV lidocaine at a lower maintenance infusion rate and monitor for toxicity. The elimination of lidocaine may be reduced in patients with severe renal impairment and accumulation of glycinexylidide (a major active metabolite) may occur, increasing the risk of toxicity.
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: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Caffeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (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; Pyrilamine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Codeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (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; Dextromethorphan: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Diphenhydramine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Hydrocodone: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (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; Ibuprofen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Oxycodone: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (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; Pamabrom; Pyrilamine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Phenylephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acetaminophen; Pseudoephedrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Acyclovir: (Moderate) Monitor for lidocaine toxicity if coadministration with acyclovir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Adagrasib: (Moderate) Monitor for lidocaine toxicity if coadministration with adagrasib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
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.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Coadministration of lidocaine with oxidizing agents, such as aminosalicylic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
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; Celecoxib: (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; 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; Valsartan; 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.
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.
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.
Apalutamide: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with apalutamide is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
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.
Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. (Moderate) Use articaine and lidocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Asciminib: (Moderate) Monitor for lidocaine toxicity if coadministration with asciminib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and asciminib is a weak CYP3A inhibitor.
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) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
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) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Avacopan: (Moderate) Monitor for lidocaine toxicity if coadministration with avacopan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and avacopan is a weak CYP3A inhibitor.
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.
Belumosudil: (Moderate) Monitor for lidocaine toxicity if coadministration with belumosudil is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and belumosudil is a weak CYP3A inhibitor.
Benzalkonium Chloride; Benzocaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (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.
Benzocaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Benzocaine; Butamben; Tetracaine: (Moderate) Use lidocaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Berotralstat: (Moderate) Monitor for lidocaine toxicity if coadministration with berotralstat is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor.
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.
Bicalutamide: (Moderate) Monitor for lidocaine toxicity if coadministration with bicalutamide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
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.
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.
Bupivacaine Liposomal: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Bupivacaine; Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Liposomal bupivacaine administration may follow lidocaine administration after a delay of 20 minutes or more. Use lidocaine and other formulations of bupivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (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.
Butalbital; Aspirin; 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.
Calamine; 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.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (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.
Cannabidiol: (Moderate) Monitor for lidocaine toxicity if coadministration with cannabidiol is necessary as concurrent use may increase lidocaine exposure. Consider a dose reduction of lidocaine as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Lidocaine is a CYP1A2 substrate and cannabidiol is a weak CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Capmatinib: (Moderate) Monitor for lidocaine toxicity if coadministration with capmatinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and capmatinib is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
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.
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 strong 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.
Chlordiazepoxide; Amitriptyline: (Major) If epinephrine is added to lidocaine for the purpose of infiltration and nerve block or spinal anesthes
Chloroprocaine: (Moderate) Use lidocaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chloroquine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as chloroquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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; 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.
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) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
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) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
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; 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.
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.
Colistin: (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.
Conivaptan: (Moderate) Monitor for lidocaine toxicity if coadministration with conivaptan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
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 CYP3A inhibitor.
Cyclophosphamide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as cyclophosphamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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) Coadministration of lidocaine with dalfopristin; quinupristin may result in elevated lidocaine plasma concentrations. If these drugs are used together, closely monitor for signs of lidocaine-related adverse events. Lidocaine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
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.
Dapsone: (Moderate) Coadministration of dapsone with lidocaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
Daratumumab; 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.
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) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (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) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
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.
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.
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.
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: (Contraindicated) 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.
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.
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 Disoproxil Fumarate: (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; Lamivudine; Tenofovir Disoproxil Fumarate: (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).
Efgartigimod Alfa; 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.
Elagolix: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
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.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with cobicistat is necessary. Lidocaine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Enzalutamide: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with enzalutamide is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
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.
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.
Everolimus: (Moderate) Monitor for lidocaine toxicity if coadministration with everolimus is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and everolimus is a weak CYP3A4 inhibitor.
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.
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.
Flutamide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Food: (Major) Advise patients to avoid cannabis use during lidocaine treatment due to decreased exposure of lidocaine which may alter its efficacy. Cannabis use induces CYP1A2 and lidocaine is a CYP1A2 substrate. The induction potential of cannabis is greatest with chronic inhalation. Other routes of administration or sporadic use may have less of an effect.
Fosamprenavir: (Moderate) Monitor for lidocaine toxicity if coadministration with fosamprenavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Moderate) Concomitant use of systemic lidocaine and fosphenytoin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; fosphenytoin induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as fosphenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
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.
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.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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; 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.
Hydroxyurea: (Moderate) Coadministration of lidocaine with oxidizing agents, such as hydroxyurea, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Ibuprofen; 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.
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.
Ifosfamide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as ifosfamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Imatinib: (Moderate) Monitor for lidocaine-related toxicity when administering with imatinib; lidocaine exposure may increase. Imatinib is a moderate CYP3A4 inhibitor; lidocaine is a CYP3A4 substrate.
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: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine 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) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifampin is necessary; higher doses of lidocaine may be required. Lidocaine is a substrate of CYP3A and CYP1A2, and rifampin is a strong CYP3A inducer and CYP1A2 inducer.
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) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifampin is necessary; higher doses of lidocaine may be required. Lidocaine is a substrate of CYP3A and CYP1A2, and rifampin is a strong CYP3A inducer and CYP1A2 inducer.
Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Isosorbide Mononitrate: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
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.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class IB antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lamotrigine: (Moderate) Consider ECG monitoring before and during concomitant use of lamotrigine with other sodium channel blockers known to impair atrioventricular and/or intraventricular cardiac conduction, such as class IB antiarrhythmics. Concomitant use of class IB antiarrhythmics with lamotrigine may increase the risk of proarrhythmia, especially in patients with clinically important structural or functional heart disease. In vitro testing showed that lamotrigine exhibits class IB antiarrhythmic activity at therapeutically relevant concentrations.
Lansoprazole; Amoxicillin; 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.
Lapatinib: (Major) Monitor for lidocaine toxicity if coadministration with lapatinib is necessary. Concomitant use of systemic lidocaine and lapatinib may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Lidocaine is a CYP3A4 substrate and lapatinib is a weak CYP3A4 inhibitor.
Lenacapavir: (Moderate) Monitor for lidocaine toxicity if coadministration with lenacapavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Leniolisib: (Moderate) Monitor for lidocaine toxicity if coadministration with leniolisib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. Coadministration with another CYP1A2 inhibitor increased lidocaine exposure by 71%.
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.
Letermovir: (Moderate) An increase in the plasma concentration of lidocaine may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Lidocaine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Levamlodipine: (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.
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.
Levoketoconazole: (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.
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; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Lidocaine; Prilocaine: (Moderate) Use lidocaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lonafarnib: (Moderate) Monitor for lidocaine toxicity if coadministration with lonafarnib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
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.
Mafenide: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Maribavir: (Moderate) Monitor for lidocaine toxicity if coadministration with maribavir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and maribavir is a weak CYP3A inhibitor.
Menthol; 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.
Meperidine: g> (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.
Mepivacaine: (Moderate) Use mepivacaine and lidocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Metoclopramide: (Moderate) Coadministration of lidocaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Metoprolol; 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.
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.
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) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
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: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
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.
Neostigmine; Glycopyrrolate: (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, Fosnetupitant; 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) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Nevirapine: (Minor) Monitor for reduced efficacy of lidocaine if coadministration with nevirapine is necessary. Concomitant use may decrease lidocaine exposure. Lidocaine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
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.
Nirmatrelvir; 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.
Nitrates: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitrofurantoin: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrofurantoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Nitroglycerin: (Moderate) Coadministration of lidocaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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) Monitor for lidocaine toxicity if coadministration with obeticholic acid is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and obeticholic acid is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Olanzapine; 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.
Olmesartan; 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.
Omeprazole; Amoxicillin; 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.
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.
Osilodrostat: (Moderate) Monitor for lidocaine toxicity if coadministration with osilodrostat is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 and CYP3A4 substrate; osilodrostat is a moderate CYP1A2 inhibitor and weak CYP3A4 inhibitor.
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.
Pacritinib: (Moderate) Monitor for lidocaine toxicity if coadministration with pacritinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 and CYP1A2 substrate; pacritinib is a weak CYP3A4 and CYP1A2 inhibitor.
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) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
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.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as lidocaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as lidocaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Pertuzumab; Trastuzumab; 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.
Phenelzine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Phenobarbital: (Moderate) Concomitant use of systemic lidocaine and phenobarbital may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenobarbital induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of systemic lidocaine and phenobarbital may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenobarbital induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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: (Moderate) Concomitant use of systemic lidocaine and phenytoin may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenytoin induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as phenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Pirtobrutinib: (Moderate) Monitor for lidocaine toxicity if coadministration with pirtobrutinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and pirtobrutinib is a weak CYP3A inhibitor.
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.
Pramoxine; Zinc Acetate: (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.
Prilocaine: (Moderate) Use lidocaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. (Moderate) Use lidocaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Primaquine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as primaquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Primidone: (Moderate) Concomitant use of systemic lidocaine and primidone may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; phenobarbital, the active metabolite of primidone, induces both hepatic isoenzymes. Additionally, coadministration of lidocaine with oxidizing agents, such as primidone, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
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.
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.
Propranolol; 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.
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. Additionally, coadministration of lidocaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Rasburicase: (Moderate) Coadministration of lidocaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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) Monitor for lidocaine-related adverse reactions if coadministration with ribociclib is necessary. Lidocaine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with ribociclib is necessary. Lidocaine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
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) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifampin is necessary; higher doses of lidocaine may be required. Lidocaine is a substrate of CYP3A and CYP1A2, and rifampin is a strong CYP3A inducer and CYP1A2 inducer.
Rifapentine: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with rifapentine is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ritlecitinib: (Moderate) Monitor for lidocaine toxicity if coadministration with ritlecitinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 and CYP3A substrate and ritlecitinib is a moderate CYP1A2 and CYP3A inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
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) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Ropivacaine: (Moderate) Use lidocaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rucaparib: (Moderate) Monitor for an increase in lidocaine-related adverse reactions if coadministration with rucaparib is necessary. Lidocaine is a CYP1A2 substrate and rucaparib is a moderate CYP1A2 inhibitor. Coadministration may increase lidocaine plasma concentrations.
Saquinavir: (Contraindicated) 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.
Selpercatinib: (Moderate) Monitor for lidocaine toxicity if coadministration with selpercatinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and selpercatinib is a weak CYP3A4 inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy of lidocaine if coadministration of systemic lidocaine with taurursodiol is necessary; higher doses of lidocaine may be required. Lidocaine is a CYP1A2 substrate and taurursodiol is a CYP1A2 inducer.
Spironolactone: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for lidocaine toxicity if coadministration with spironolactone is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and spironolactone is a weak CYP3A4 inhibitor.
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) Coadministration of lidocaine with dalfopristin; quinupristin may result in elevated lidocaine plasma concentrations. If these drugs are used together, closely monitor for signs of lidocaine-related adverse events. Lidocaine is a substrate of CYP3A; dalfopristin; quinupristin is a weak CYP3A inhibitor.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
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.
Sulfadiazine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfasalazine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Sulfonamides: (Moderate) Coadministration of lidocaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
Telmisartan; 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.
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: (Moderate) Use tetracaine and lidocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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.
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.
Tramadol; Acetaminophen: (Moderate) Coadministration of lidocaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
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: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
Trastuzumab; 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.
Tretinoin; 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.
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.
Trofinetide: (Moderate) Monitor for lidocaine toxicity if coadministration with trofinetide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and trofinetide is a weak CYP3A inhibitor.
Tucatinib: (Moderate) Monitor for lidocaine toxicity if coadministration with tucatinib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valproic Acid, Divalproex Sodium: (Moderate) Coadministration of lidocaine with oxidizing agents, such as valproic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
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.
Viloxazine: (Moderate) Monitor for lidocaine toxicity if coadministration with viloxazine is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 and CYP3A substrate and viloxazine is a strong CYP1A2 and weak CYP3A inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Vonoprazan; Amoxicillin: (Moderate) Monitor for lidocaine toxicity if coadministration with vonoprazan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; 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 togethe r. Lidocaine is a CYP3A4 and CYP1A2 substrate; clarithromycin inhibits CYP3A4. (Moderate) Monitor for lidocaine toxicity if coadministration with vonoprazan is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Moderate) Monitor for lidocaine-related adverse reactions if coadministration with voriconazole is necessary. Lidocaine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Monitor for lidocaine toxicity if coadministration with voxelotor is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as lidocaine.
Zileuton: (Moderate) Monitor for lidocaine toxicity if coadministration with zileuton is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and zileuton is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
How Supplied
7T Lido/ALOCANE/Astero/DermacinRx Lidogel/DermacinRx Lidorex/LidoRx/SUN BURNT PLUS/Tranzarel Topical Gel: 2%, 2.8%, 3%, 4%
7T Lido/Anestacon/Glydo/Lidocaine/Lidocaine Hydrochloride/Xylocaine/Xylocaine Topical Jelly Topical Jelly: 2%
Akten Ophthalmic Gel: 3.5%
ALOCANE/Aspercreme with Lidocaine/Blue-Emu/GEN7T/Lidocaine/Lidocare/Lidofore/LidoReal-30/Salonpas Lidocaine Topical Film: 3.5%, 4%
ALOCANE/Aspercreme with Lidocaine/Lidocaine/Lidocaine Hydrochloride Topical Spray: 4%
ANASTIA/GEN7T/Lidocaine/Lidocaine Hydrochloride/LIDO-K/LIDO-SORB/LIDOZION/Numbonex/Senatec/Zionodi Topical Lotion: 2.75%, 3%, 3.5%
AneCream/Aspercreme with Lidocaine/BenGay/Blue Tube/CidalEaze/Gold Bond/LidaMantle/Lidocaine/Lidocaine Hydrochloride/LidoHeal-90/Lidosense 4/Lidotral/LMX 4/LMX 4 with Tegaderm/LMX 5/Lydexa/RectaSmoothe/RectiCare Topical Cream: 3%, 3.88%, 4%, 4.12%, 5%
Aspercreme with Lidocaine/Blue-Emu/GEN7T/Lidocaine/Lidocare/Lidofore/Lidozo/Salonpas Lidocaine Transdermal Film: 3.5%, 4%
Aspercreme with Lidocaine/Lidocaine/Lidocaine Hydrochloride/VacuStim Silver/Xylocaine/Xylocaine Topical Solution/Zilactin-L Topical Sol: 1mL, 4%, 40mg
DERMALID/Lidocaine/Lidocan/Lidoderm/Xyliderm/ZTlido Transdermal Film ER: 1.8%, 5%
Lidocaine Rectal Supp: 50mg
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/Lidomark/Xylocaine/Xylocaine MPF Epidural Inj Sol: 0.5%, 1%, 1.5%, 2%
Lidocaine/Lidocaine Hydrochloride/Lidomark/Xylocaine/Xylocaine MPF Infiltration Inj Sol: 0.5%, 1%, 1.5%, 2%
Lidocaine/Lidocaine Hydrochloride/Lidomark/Xylocaine/Xylocaine MPF Intracaudal Inj Sol: 1%, 1.5%, 2%
Lidocaine/Lidocaine Hydrochloride/Xylocaine MPF Retrobulbar Inj Sol: 4%
Lidocaine/Lidocaine Hydrochloride/Xylocaine MPF Topical Inj Sol: 4%
Lidocaine/Lidocaine Hydrochloride/Xylocaine/Xylocaine MPF Percutaneous Inj Sol: 0.5%, 1%
Lidocaine/Lidocaine Hydrochloride/Xylocaine/Xylocaine MPF Perineural Inj Sol: 1%, 2%
Lidocaine/Lidocaine Hydrochloride/Zingo Intradermal Pwd: 0.5mg
Lidocaine/Lidosol/Lidosol-50/Lidovix L/MENTHO-CAINE/Moxicaine/SOLUPAK/ZiloVal Topical Ointment: 5%
LidoDose/LidoDose Pediatric Topical Swab: 3%
Xylocaine Topical Jelly Urethral Jelly: 2%
Maximum Dosage
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.
Adults100 mg/dose IV load (may repeat to a Max total load of 300 mg over a 1 hour period) for perfusing ventricular arrhythmias or 1.5 mg/kg/dose IV load (may repeat to a Max total load of 3 mg/kg) for ventricular arrhythmias during CPR; 4 mg/minute (50 mcg/kg/minute) IV continuous infusion for ventricular arrhythmias; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
Geriatric100 mg/dose IV load (may repeat to a Max total load of 300 mg over a 1 hour period) for perfusing ventricular arrhythmias or 1.5 mg/kg/dose IV load (may repeat to a Max total load of 3 mg/kg) for ventricular arrhythmias during CPR; 4 mg/minute (50 mcg/kg/minute) IV continuous infusion for ventricular arrhythmias; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
Adolescents1 mg/kg (Max: 100 mg) IV loading dose, up to 3 mg/kg (Max: 300 mg) IV total loading dose, and 50 mcg/kg/minute IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
Children1 mg/kg (Max: 100 mg) IV loading dose, up to 3 mg/kg (Max: 300 mg) IV total loading dose, and 50 mcg/kg/minute IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
Infants1 mg/kg IV loading dose, up to 3 mg/kg IV total loading dose, and 50 mcg/kg/minute IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
Neonates1 mg/kg IV loading dose, up to 3 mg/kg IV total loading dose, and 50 mcg/kg/minute IV continuous infusion for ventricular arrhythmias; 2 mg/kg IV loading dose and 6 mg/kg/hour IV continuous infusion for status epilepticus; maximum dosage for use as a topical or local anesthetic is dependent on the indication, route, and formulation used.
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 stabilizes neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.[44097] 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 2 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% to 36% and from 5% to 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 to 30 minutes, followed by a terminal half-life of 1.5 to 2 hours. The half-life of MEGX is 0.5 to 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 2 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.
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 RouteAfter intravenous injection, lidocaine distributes in 2 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 to 1.3 L/kg. The onset of action of intravenous doses is immediate. The duration of action is 10 to 20 minutes with an intravenous dose, although this is highly dependent on hepatic function.
Intramuscular RouteThe onset of action of an intramuscularly administered dose is 5 to 15 minutes. The duration of action is 60 to 90 minutes with an intramuscular dose, although this is highly dependent on hepatic function.
Subcutaneous RouteOnly 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 to 3 hours, depending upon the strength of the preparation used. The addition of epinephrine 5 to 10 mcg/mL slows the vascular absorption of lidocaine and prolongs its effects.
Topical RouteThe rate and extent of absorption after topical administration is dependent the concentration, total dose, site of application, and duration of exposure. The most rapid rate of absorption generally occurs after intratracheal administration. After topical administration of ointment or jelly, peak effects typically occur within 3 to 5 minutes.
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.
Lidocaine topical system (ZTlido) 1.8% demonstrated equivalent AUC and Cmax of lidocaine to lidocaine dermal patch 5%. After application of 3 lidocaine topical systems over a 420 cm2 area of intact skin on the backs of 54 healthy volunteers for 12 hours, mean plasma Cmax was 75.1 (+/- 23) ng/mL and mean Tmax was 13.9 (4, 18) hours. Systemic lidocaine concentrations did not increase with daily use. Exposure to external heat source (heating pad at medium setting applied for 20 minutes at time 0 and 8.5 hours) increased lidocaine mean peak plasma concentrations from 97.6 +/- 36.9 ng/mL to 160.3 +/- 100.1 ng/mL. Moderate exercise (cycling at a heart rate of 108 bpm) at time 0, 2.5, 5.5, and 8.5 hours produced no clinically relevant differences in systemic absorption with mean peak plasma concentrations of 90.5 +/- 25.4 ng/mL. There were no significant pharmacokinetic differences when the system was applied to the administration site after external heat exposure (heating pad at medium setting applied for 15 minutes prior to system application) or after moderate walking for approximately 20 minutes beginning approximately 30 minutes prior to system application.
Local anesthesia starts to occur within 2.5 minutes of application of the transoral patch (DentiPatch) to intact mucous membranes. During 15 minutes of system application, serum concentrations of lidocaine are less than 0.1 mcg/mL. After removal of the patch after 15 minutes of application, local anesthesia continues for approximately 30 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 to 3 minutes of application. Analgesia diminishes within 10 minutes of administration. In adults, lidocaine plasma concentrations were undetectable (less than 5 ng/mL) after a single dose of Zingo.
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 to 30 minutes with a mean duration of 15 minutes.
Pregnancy And Lactation
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.