Lidocaine

Mechanism of Action

Lidocaine HCl stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.

Hemodynamics

Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded.

Pharmacokinetics and Metabolism

Information derived from diverse formulations, concentrations and usages reveals that lidocaine HCl is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.

The plasma binding of lidocaine HCl is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base per mL 60 to 80 percent of lidocaine HCl is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Lidocaine HCl crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine HCl is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of lidocaine HCl. Approximately 90% of lidocaine HCl administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.

The elimination half-life of lidocaine HCl following an intravenous bolus injection is typically 1.5 to 2.0 hours. Because of the rapid rate at which lidocaine HCl is metabolized, any condition that affects liver function may alter lidocaine HCl kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine HCl kinetics but may increase the accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of lidocaine HCl required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0μg free base per mL. In the rhesus monkey arterial blood levels of 18–21 µg/mL have been shown to be threshold for convulsive activity.

Store lidocaine at room temperature.

Keep this and all medicines out of the reach of children.

You should not receive this medication if you are allergic to lidocaine or any other type of numbing medicine.

Before you receive lidocaine injection, tell your doctor if you have liver or kidney disease, heart disease, coronary artery disease, circulation problems, or a history of malignant hyperthermia.

To treat irregular heart rhythms, your doctor may prescribe a LidoPen auto-injector. This is a prefilled automatic injection device to be used in an emergency. Keep the device with you at all times.

Your doctor will describe the signs and symptoms to watch for when deciding when it's time to use lidocaine injection at home. Never use the LidoPen auto-injector without first calling your doctor.

With the LidoPen auto-injector you will also receive a CardioBeeper to transmit your heart rate and rhythm to your doctor over a telephone. Read all provided instructions and practice using the CardioBeeper.

Lidocaine can cause side effects that may impair your thinking or reactions. Unless absolutely necessary, do not drive after using this medication

Since lidocaine injection is used only when needed, you are not likely to be on a dosing schedule.

Never use the LidoPen auto-injector without first calling your doctor.

Lidocaine hydrochloride is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type. 

Lidocaine HYDROCHLORIDE INJECTION, USP FOR INFILTRATION AND NERVE BLOCK SHOULD BE EMPLOYED ONLY BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER ENSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT AND THE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES. (See also ADVERSE REACTIONS and PRECAUTIONS.) DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST AND, POSSIBLY, DEATH.

Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been postmarketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.

To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.

Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of  local anesthetic solution (see ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS).

Management of Local Anesthetic Emergencies

The first consideration is prevention best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient’s state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered.

The first step in the management of convulsions, as well as underventilation or apnea due to unintended subarachnoid injection of drug solution, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to the use of local anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor as directed by the clinical situation (e.g., ephedrine).

If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. Underventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.

Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated.

Dialysis is of negligible value in the treatment of acute overdosage with Lidocaine hydrochloride. The oral LD50 of Lidocaine hydrochloride in non-fasted female rats is 459 (346 to 773) mg/kg (as the salt) and 214 (159 to 324) mg/kg (as the salt) in fasted female rats.

NOTE: The products accompanying this insert do not contain epinephrine. 

Adults

For normal healthy adults, the individual maximum recommended dose of Lidocaine hydrochloride with epinephrine should not exceed 7 mg/kg (3.5 mg/lb) of body weight, and in general it is recommended that the maximum total dose not exceed 500 mg. When used without epinephrine the maximum individual dose should not exceed 4.5 mg/kg (2 mg/lb) of body weight, and in general it is recommended that the maximum total dose does not exceed 300 mg. For continuous epidural or caudal anesthesia, the maximum recommended dosage should not be administered at intervals of less than 90 minutes. When continuous lumbar or caudal epidural anesthesia is used for non-obstetrical procedures, more drug may be administered if required to produce adequate anesthesia.

The maximum recommended dose per 90 minute period of  Lidocaine hydrochloride for paracervical block in obstetrical patients and non-obstetrical patients is 200 mg total. One half of the total dose is usually administered to each side. Inject slowly, five minutes between sides. (See also discussion of paracervical block in PRECAUTIONS.)

For intravenous regional anesthesia, the dose administered should not exceed 4 mg/kg in adults.

Children

It is difficult to recommend a maximum dose of any drug for children, since this varies as a function of age and weight. For children over 3 years of age who have a normal lean body mass and normal body development, the maximum dose is determined by the child’s age and weight. For example, in a child of 5 years weighing 50 lbs the dose of Lidocaine hydrochloride should not exceed 75 to 100 mg (1.5 to 2 mg/lb). The use of even more dilute solutions (i.e., 0.25 to 0.5%) and total dosages not to exceed 3 mg/kg (1.4 mg/lb) are recommended for induction of intravenous regional anesthesia in children.

In order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose should be used at all times. In some cases it will be necessary to dilute available concentrations with 0.9% sodium chloride injection in order to obtain the required final concentration.

NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. Do not use if solution is discolored or contains a precipitate.

THE ABOVE SUGGESTED CONCENTRATIONS AND VOLUMES SERVE ONLY AS A GUIDE. OTHER VOLUMES AND CONCENTRATIONS MAY BE USED PROVIDED THE TOTAL MAXIMUM RECOMMENDED DOSE IS NOT EXCEEDED.

Rx only             NDC 55150-161-02
Lidocaine
HCl Injection, USP
1%    20 mg/2 mL
       (10 mg/mL)
Preservative-Free
2 mL                     Single Dose Vial
 

Rx only               NDC 55150-164-02
Lidocaine
HCl Injection, USP
2%    40 mg/2 mL
       (20 mg/mL)
Preservative-Free
2 mL                     Single Dose Vial
 
 
 

The following serious adverse reactions are described elsewhere in the labeling:

• Application Site Reactions [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]

The following adverse reactions from voluntary reports or clinical studies have been reported with lidocaine. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin And Subcutaneous Tissues: blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erosions, erythema, exfoliation, flushing, irritation, papules, petechia, pruritus, vesicles, and abnormal sensation.

Immune system: angioedema, bronchospasm, dermatitis, dyspnea, hypersensitivity, laryngospasm, pruritus, shock, and urticaria.

Central Nervous System: lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, somnolence, respiratory depression and arrest.

Cardiovascular: bradycardia, hypotension, and cardiovascular collapse leading to arrest.

Other: asthenia, disorientation, headache, hyperesthesia, hypoesthesia, metallic taste, nausea, pain exacerbated, paresthesia, taste alteration, and vomiting.

ZTLIDO™
(ZEE-TEE-LIE-DOH)
(lidocaine topical system)

What is ZTLIDO?

ZTLIDO is a prescription medicine used for relief of pain from damaged nerves (neuropathic pain) that follows healing of shingles. It is not known if ZTLIDO is safe and effective in children.

Do not use ZTLIDO if you:

• have a history of allergic reactions to numbing medicines (anesthetics). Ask your healthcare provider if you are not sure.
• are allergic to any of the ingredients in ZTLIDO. See the end of this leaflet for a complete list of ingredients in ZTLIDO.

Before using ZTLIDO, tell your healthcare provider about all your medical conditions, including if you:

• have liver problems.
• are allergic to para-aminobenzoic acid (PABA) medicines such as procaine, tetracaine, or benzocaine.
• are pregnant or plan to become pregnant. It is not known if ZTLIDO will harm your unborn baby.
• are breastfeeding or plan to breastfeed. ZTLIDO can pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use ZTLIDO.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially, tell your healthcare provider if you are using other lidocaine containing products or anesthetic medicines.

How should I use ZTLIDO?

Read the Instructions for Use at the end of this Patient Information leaflet for information about how to apply the ZTLIDO topical system.

• Use ZTLIDO exactly as your healthcare provider tells you to use it.
• Do not apply more than your prescribed number of ZTLIDO. You may apply up to 3 ZTLIDO topical systems at one time.
• A ZTLIDO may be worn only 1 time for up to 12 hours within a 24-hour period (12 hours on and 12 hours off).
• Apply ZTLIDO to intact skin only. Do not apply ZTLIDO to skin that is not intact, such as skin that is cut, scraped, burned, or irritated.
• ZTLIDO topical systems that are lifting at the edges maybe reattached by firmly pressing down on the edges.
• If the ZTLIDO you are wearing comes off completely, and will not stick to your skin, throw away the used ZTLIDO. You may apply a replacement (a new) ZTLIDO. Take off the replacement ZTLIDO at your usual removal time. The total time you may wear the used and replacement ZTLIDO should not be more than 12 hours.
• You may wear clothing over the ZTLIDO application site.
• Do not apply external heat sources, such as heating pads or electric blankets, directly on ZTLIDO. This may cause increased levels of lidocaine in your blood. You may apply ZTLIDO to a treatment site after moderate heat exposure, such as after 15 minutes of heating pad use on a medium setting.
• ZTLIDO may be used during moderate exercise, such as biking for 30 minutes.
• After using ZTLIDO, fold the used ZTLIDO so that the sticky sides stick together. Safely throw away used ZTLIDO and any pieces of cut ZTLIDO where children and pets cannot get to them.
• Wash your hands right away after applying or handling ZTLIDO.
• If you start feeling irritation or burning when applying ZTLIDO, remove the ZTLIDO. Do not reapply ZTLIDO until the irritation or burning goes away.
• If you apply more than 3 ZTLIDO topical systems or apply ZTLIDO for longer than 12 hours of a 24-hour period, call your healthcare provider.

What should I avoid while using ZTLIDO?

• Avoid contact with water, such as bathing, swimming, or showering while wearing ZTLIDO. ZTLIDO may not stick if it gets wet. Avoid contact of your hands and fingers with your eyes while handling ZTLIDO.

What are the possible side effects of ZTLIDO?

ZTLIDO may cause serious side effects, including:

• Lidocaine overdose can happen if you apply more than the prescribed number of ZTLIDO, applying ZTLIDO for longer than 12 hours, have liver problems, use ZTLIDO on skin that is not intact, or if you apply external heat sources directly on ZTLIDO. This can result in increased levels of lidocaine in your blood.
  • Do not apply more than the prescribed number of ZTLIDO.
  • Do not wear ZTLIDO longer than 12 hours.
  • Do not apply ZTLIDO on skin that is not intact, such as skin that is cut, scraped, burned, or irritated.
  • Do not apply external heat sources directly to ZTLIDO. See “How should I use ZTLIDO?” for more information about how to properly use external heat sources when using ZTLIDO.
• Application site reactions. Skin reactions at the ZTLIDO application site are common and are usually mild, but can be severe if ZTLIDO is applied for a longer period of time than prescribed. These reactions can happen during or right after treatment with ZTLIDO. Application site reactions will usually go away within a few minutes to hours. Symptoms of application site reactions may include:
  • blisters
  • peeling or flaking of skin
  • bruising
  • irritation
  • burning or abnormal sensation
  • pimple-like raised skin
  • change or loss of color of your skin
  • itching
  • swelling, redness, and pain of the skin
• Allergic reactions can happen if you have a history of allergic reactions to numbing medicines (anesthetics). Tell your healthcare provider right away if you have any symptoms of an allergic reaction such as swelling or shortness of breath.
• Contact of ZTLIDO with your eyes can happen if you touch your eyes while handling the topical system and can cause severe eye irritation. Avoid eye contact with your hands and fingers while handling ZTLIDO. Wash your hands right away after handling ZTLIDO. If the medicine in ZTLIDO comes in contact with your eye, wash out your eye with water or saline right away. Protect the eye (for example eye glasses or eye wear) until the numbness goes away.

These are not all the possible side effects of ZTLIDO.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store ZTLIDO?

• Store ZTLIDO at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep ZTLIDO topical system in the original packaging unit until ready for use.

Keep ZTLIDO and all medicines out of the reach of children, pets, and others.

General information about the safe and effective use of ZTLIDO.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ZTLIDO for a condition for which it was not prescribed. Do not give ZTLIDO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about ZTLIDO that is written for health professionals.

What are the ingredients in ZTLIDO?

Active ingredient: lidocaine

Inactive ingredients: butylated hydroxytoluene, dipropylene glycol, isostearic acid, mineral oil, polyisobutylene, silicone dioxide, styrene/isoprene/styrene block copolymer, and terpene resin.

Instructions for Use

ZTLIDO™
(ZEE-TEE-LIE-DOH)
 (lidocaine topical system)

Read this Instructions for Use before you start using the ZTLIDO and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical treatment or condition.

Important information:

• One ZTLIDO (lidocaine topical system) 1.8% provides equivalent lidocaine exposure to one Lidoderm® (lidocaine patch 5%).
• ZTLIDO is for use on intact skin only.
• ZTLIDO comes in a child-resistant envelope. Do not open the ZTLIDO envelope until you are ready to use it.
• Apply the prescribed number of ZTLIDO topical systems at one time.
• You should only use a maximum of 3 ZTLIDO topical systems at a time.
• Keep your prescribed number of ZTLIDO topical systems on for up to 12 hours within a 24-hour period (12 hours on and 12 hours off).
• Avoid contact with water, such as bathing, swimming or showering while using ZTLIDO. ZTLIDO may not stick if it gets wet.
• ZTLIDO topical systems that have lifted at edges may be re-attached by pressing firmly on the edges. If a your ZTLIDO comes off completely and will not stick to your skin, it should be thrown away (see Step 6). If your ZTLIDO topical system comes off completely, you may put on a new ZTLIDO topical system for a total duration of 12 hours for used and new topical systems together.

Figure A: ZTLIDO Topical System

Applying your ZTLIDO topical system:

Step 1: Select the application site.

• ZTLIDO should only be applied to clean, dry, and intact skin to cover the most painful area.

Step 2: Using scissors, carefully cut the envelope along the dotted line and open it to remove ZTLIDO.

• Do not use ZTLIDO if it is damaged. Throw it away and get a new one.
• ZTLIDO may be cut into smaller sizes with scissors prior to removal of the transparent release liner.

Step 3a: Remove the transparent release liner before applying ZTLIDO to the skin. Apply ZTLIDO right away after removing the transparent release liner. Apply ZTLIDO only to intact skin.

Step 3b: Place the adhesive side of ZTLIDO to skin, while not touching the sticky side. Smooth the ZTLIDO using your hands and firmly press to make sure it sticks well to skin.

Step 4: Wash your hands right away after applying ZTLIDO.

• Avoid contact of your hands or fingers with your eyes until hands are washed.

Removing your ZTLIDO topical system:

Step 5: Remove ZTLIDO from you skin after you have worn it for up to 12 hours.

• Fold the used ZTLIDO so that the sticky sides stick together.

Step 6: Throw away the used whole or cut pieces of ZTLIDO where children and pets cannot get to them.

• Wash your hands right away after removing ZTLIDO.

Application of a replacement ZTLIDO (a new ZTLIDO):

• If the ZTLIDO you are wearing comes off completely and will not stick to your skin, throw away the used ZTLIDO as instructed above in Step 6.
• Apply a replacement ZTLIDO the same way you would apply a new ZTLIDO as described above in Steps 1 through 6.
• Take off the replacement ZTLIDO at your usual removal time.
• The total time you may wear the used and replacement ZTLIDO should not be more than 12 hours.

This Patient Information has been approved by the U.S. Food and Drug Administration.