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Lidocaine (Systemic)


VA CLASSIFICATION
Primary: CV300

Commonly used brand name(s): Xylocaine; Xylocard.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiarrhythmic—

Indications

Accepted

Arrhythmias, ventricular (treatment)—Lidocaine (systemic) is indicated and is the drug of choice in the acute management of ventricular arrhythmias, such as those resulting from acute myocardial infarction, digitalis toxicity, cardiac surgery, or cardiac catheterization.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

pKa—
    7.86

Mechanism of action/Effect:

Antiarrhythmic—Lidocaine decreases the depolarization, automaticity, and excitability in the ventricles during the diastolic phase by a direct action on the tissues, especially the Purkinje network, without involvement of the autonomic system. Neither contractility, systolic arterial blood pressure, atrioventricular (AV) conduction velocity, nor absolute refractory period is altered by usual therapeutic doses. In the Vaughan Williams classification of antiarrhythmics, lidocaine is a class IB agent.

Distribution:

Rapid. Volume of distribution (Vol D)—About 1 liter per kg of body weight (L/kg); reduced in heart failure patients.

Protein binding:

Moderate to high (60 to 80%; dependent on drug concentration).

Biotransformation:

90% hepatic; active metabolites, monoethylglycinexylidide and glycinexylidide, may contribute to therapeutic and toxic effects, especially after infusions lasting 24 hours or more.

Half-life:

1 to 2 hours (average about 100 minutes); dose-dependent (tends to be biphasic with the distribution phase of 7 to 9 minutes causing the short duration of action following an intravenous loading dose); increased to 3 hours or longer during prolonged intravenous infusions (longer than 24 hours) {03}.

Onset of action:

Intravenous—Immediate (45 to 90 seconds).

Time to steady-state plasma concentration

Continuous intravenous infusion—3 to 4 hours (8 to 10 hours in patients with acute myocardial infarction).

Therapeutic plasma concentration

1.5 to 5 mcg/mL (concentrations exceeding 5 mcg/mL are considered to be in the toxic range).

Duration of action:

Intravenous—10 to 20 minutes.

Elimination:
    Renal, 10% unchanged.
    In dialysis—Very little removable by dialysis {11}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other amide-type anesthetics or flecainide or tocainide may be sensitive to lidocaine also. Cross-sensitivity with procainamide or quinidine has not been reported.

Carcinogenicity/Mutagenicity

Long-term animal studies evaluating the carcinogenic or mutagenic potential of lidocaine have not been done. {04}

Pregnancy/Reproduction

Pregnancy—
Lidocaine crosses the placenta. Adequate and well-controlled studies in humans have not been done.

Studies in rats given doses up to 6.6 times the maximum human dose have not shown that lidocaine causes adverse effects in the fetus. {04} However, lidocaine has been shown to constrict uterine arteries in sheep and in experimentally isolated uterine artery segments. {06} Furthermore, studies in sheep have shown that lidocaine causes significant increases in fetal blood pressure and increases or decreases in fetal heart rate related to the rate of lidocaine infusion. {07} {08}

FDA Pregnancy Category B.

Breast-feeding

It is not known whether lidocaine is distributed into human breast milk. However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of lidocaine have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


Elderly patients are more prone to the adverse effects of lidocaine. {05} In patients over 65 years of age, dose and rate of infusion should be reduced by one half and adjusted slowly as needed and tolerated. In addition, elderly patients are more likely to have age-related renal function impairment, which may require dosage adjustment.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antiarrhythmics, other    (although some antiarrhythmic agents may be used in combination for therapeutic advantage, combined use may sometimes potentiate risk of adverse cardiac effects)


» Anticonvulsants, hydantoin    (concurrent use with lidocaine may have additive cardiac depressant effects; hydantoin anticonvulsants may also promote increased hepatic metabolism of lidocaine, reducing its intravenous concentration)


Beta-adrenergic blocking agents, systemic and ophthalmic (if systemic absorption occurs)    (concurrent use may slow hepatic metabolism and increase the risk of toxicity of lidocaine because of reduced hepatic blood flow)


Cimetidine    (concurrent administration with lidocaine may result in reduced hepatic clearance of lidocaine, possibly resulting in delayed elimination and increased blood concentrations; monitoring of blood concentrations and clinical parameters as a guide to dosage is recommended)


Neuromuscular blocking agents    (effects may be potentiated when used concurrently with large doses [such as those over 5 mg per kg] of intravenous lidocaine)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Bentiromide    (concurrent administration of lidocaine during a bentiromide test period will invalidate test results since lidocaine is also metabolized to arylamines and will thus increase the percent of PABA recovered; discontinuation of lidocaine at least 3 days prior to the administration of bentiromide is recommended)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Adams-Stokes syndrome or
» Heart block, severe, including atrioventricular, intraventricular, or sinoatrial blocks    (heart block may be worsened)


Risk-benefit should be considered when the following medical problems exist
» Congestive heart failure or
Hepatic function impairment or
» Reduced hepatic blood flow or
Renal function impairment    (accumulation may occur; dose and rate of infusion should be reduced by one half)


» Heart block, incomplete or
» Hypovolemia and shock or
» Sinus bradycardia or
» Wolff-Parkinson-White syndrome    (may be aggravated)


Sensitivity to lidocaine

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood pressure determinations and
» Electrocardiograph (ECG) determinations    (recommended throughout therapy to help adjust dosage and detect toxicity; intravenous infusion of lidocaine should be promptly discontinued if ECG determinations show a prolonged PR interval and QRS complex or if arrhythmias occur or become worse)


Electrolyte concentrations, serum    (periodic to allow imbalance corrections during prolonged infusions)


Lidocaine concentrations, serum    (useful to avoid toxicity during prolonged or high-dose infusions or in patients receiving drugs that alter lidocaine clearance)




Side/Adverse Effects

Note: Adverse effects are dose- and age-related; incidence is increased in patients over 65 years of age.
Adverse cardiovascular effects at therapeutic doses are rare, except in patients with existing compromised ventricular function. Cardiac conduction disturbances are extremely rare. High plasma lidocaine concentrations may lead to hypotension, arrhythmias, heart block, and respiratory and cardiac arrest.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Allergic reaction (difficulty in breathing; itching; skin rash; swelling of skin)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
    
Pain at site of injection —with prolonged intravenous use

Incidence dose-related
With serum lidocaine concentrations of 1.5 to 6 mcg/mL
    
Anxiety or nervousness
    
dizziness
    
drowsiness
    
feelings of coldness, heat, or numbness






Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
With serum lidocaine concentrations of 6 to 8 mcg/mL
    
Blurred or double vision
    
nausea or vomiting
    
ringing in ears
    
tremors or twitching

With serum lidocaine concentrations of > 8 mcg/mL
    
Difficulty in breathing
    
dizziness, severe, or fainting
    
seizures
    
slow heartbeat


Treatment of overdose


For severe reactions:
Stopping administration of lidocaine; monitoring patient closely.

Maintenance of airway and administration of oxygen.



Specific treatment:
For circulatory depression—Administration of a vasopressor (such as ephedrine or metaraminol) and intravenous fluids if necessary.

For seizures—If no satisfactory response to respiratory support is obtained, diazepam in 2.5-mg increments, or an ultra-short-acting barbiturate (such as thiopental or thiamylal) in 50- to l00-mg increments, is often beneficial. Caution must be maintained because of possible additive circulatory depression. If patient is under anesthesia, a short-acting muscle relaxant (such as succinylcholine) administered intravenously is sometimes helpful. When such relaxants are used, ability to provide artificial respiration is mandatory.



General Dosing Information
See also Patient monitoring.

Dosage should be adjusted to meet the individual requirements of each patient, on the basis of clinical response.

The use of lidocaine necessitates concurrent ECG monitoring and the availability of oxygen, resuscitation equipment, and emergency medications for the management of possible adverse reactions involving the cardiovascular system and/or central nervous system (CNS) as well as possible allergic reactions.
For intravenous administration
Lidocaine for intravenous administration must not contain preservatives or other medications such as epinephrine.

The preferred diluent for lidocaine infusion is 5% dextrose injection.

Lidocaine must not be added to blood transfusions.

To achieve optimal control of lidocaine dosage and rate of administration, it is recommended that lidocaine be administered intravenously by means of an infusion pump, a microdrip regulator, or a similar device that allows precise adjustment of the flow rate.

A loading dose of lidocaine is commonly administered for the initial intravenous dose to partially compensate for its rapid perfusion and distribution, which tend to delay attainment of a therapeutic serum concentration. If the initial loading dose does not provide the desired effect within 5 minutes, a second loading dose reduced to one half to one third of the first dose may be given.

Dosage reduction may be required with prolonged intravenous infusions (longer than 24 hours) because of the risk of accumulation.



Parenteral Dosage Forms

LIDOCAINE HYDROCHLORIDE INJECTION (FOR CONTINUOUS INTRAVENOUS INFUSION) USP

Usual adult dose
Antiarrhythmic
Continuous intravenous infusion (usually following a loading dose), 1 to 4 mg per minute (20 to 50 mcg per kg of body weight per minute). {12}


Note: Infusion rates should be decreased in older patients and patients with congestive heart failure or hepatic dysfunction to avoid lidocaine toxicity. {12}


Usual adult prescribing limits
300 mg (about 4.5 mg per kg of body weight) in any one-hour period.

Usual pediatric dose
Antiarrhythmic
Continuous intravenous infusion (usually following a loading dose), 30 mcg (range, 20 to 50 mcg) (0.03 mg; range, 0.02 to 0.05 mg) per kg of body weight per minute. Rate of infusion should not exceed usual adult rate of 4 mg per minute.


Strength(s) usually available
U.S.—


4% w/v (40 mg per mL [1 gram per 25 mL or 2 grams per 50 mL]) (Rx) [Xylocaine (preservative-free)][Generic](may contain methylparaben)


10% w/v (100 mg per mL [1 gram per 10 mL]) (Rx)[Generic](may contain methylparaben)


20% w/v (200 mg per mL [1 gram per 5 mL or 2 grams per 10 mL]) (Rx) [Xylocaine (preservative-free)][Generic](may contain methylparaben)

Canada—


2% (20 mg per mL [1 gram per 50 mL]) (Rx) [Xylocard]


20% (200 mg per mL [1 gram per 5 mL]) (Rx) [Xylocard]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F). Protect from freezing.

Preparation of dosage form:
To prepare solution for intravenous infusion, add 1 gram of lidocaine hydrochloride (25 mL of 4% or 5 mL of 20% Lidocaine Hydrochloride Injection USP) to 1 liter of 5% dextrose injection; the resultant concentration will be 1 mg per mL. Check manufacturer's package insert for additional dilution information.

Stability:
After dilution in the appropriate intravenous solution for infusion, lidocaine hydrochloride is stable for at least 24 hours.

Auxiliary labeling:
Following dilution, a label stating the concentration of the lidocaine hydrochloride contents with time and date of dilution should be placed on the infusion solution container.


LIDOCAINE HYDROCHLORIDE INJECTION (FOR DIRECT INTRAVENOUS INJECTION) USP

Usual adult dose
Antiarrhythmic
Direct intravenous injection, 1 mg per kg of body weight (usually 50 to 100 mg) as a loading dose at a rate of about 25 to 50 mg per minute, the dose being repeated after five minutes if necessary; usually followed by continuous intravenous infusion of lidocaine to maintain antiarrhythmic effects.


Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Usual adult prescribing limits
300 mg (about 4.5 mg per kg of body weight) in any one-hour period.

Usual pediatric dose
Antiarrhythmic
Direct intravenous injection, 1 mg per kg of body weight as a loading dose at a rate of about 25 to 50 mg per minute, the dose being repeated after five minutes if necessary but not exceeding a total dose of 3 mg per kg; usually followed by continuous intravenous infusion of lidocaine to maintain antiarrhythmic effects.


Strength(s) usually available
U.S.—


1% w/v (10 mg per mL [50 mg per 5 mL or 100 mg per 10 mL]) (Rx) [Xylocaine (preservative-free)][Generic](may contain methylparaben)


2% w/v (20 mg per mL [100 mg per 5 mL]) (Rx) [Xylocaine ( preservative-free)][Generic]( may contain methylparaben)

Canada—


2% w/v (20 mg per mL [100 mg per 5 mL]) (Rx) [Xylocard][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F). Protect from freezing.

Stability:
When dilution is required, it should be done immediately prior to direct intravenous administration.


STERILE LIDOCAINE HYDROCHLORIDE USP

Usual adult dose
Antiarrhythmic
Continuous intravenous infusion (usually following a loading dose), 1 to 4 mg per minute (20 to 50 mcg per kg of body weight per minute). {12}


Note: Infusion rates should be decreased in older patients and patients with congestive heart failure or hepatic dysfunction to avoid lidocaine toxicity. {12}


Usual adult prescribing limits
300 mg (about 4.5 mg per kg of body weight) in any one-hour period.

Usual pediatric dose
Antiarrhythmic
Continuous intravenous infusion (usually following a loading dose), 30 mcg (0.03 mg) (range, 20 to 50 mcg) per kg of body weight per minute. Rate of infusion should not exceed usual adult rate of 4 mg per minute.


Size(s) usually available:
U.S.—


1 gram (Rx)[Generic]


2 grams (Rx)[Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F).

Preparation of dosage form:
Sterile Lidocaine Hydrochloride USP is prepared for continuous intravenous infusion by adding 1 or 2 grams to 1000 mL of 5% dextrose injection, producing a solution containing 1 or 2 mg of lidocaine hydrochloride per mL, respectively {02}. Check manufacturer's package insert for additional dilution information.

Stability:
After dilution in the appropriate intravenous solution for infusion, lidocaine hydrochloride is stable for at least 24 hours.

Auxiliary labeling:
Following dilution, a label stating the concentration of the lidocaine hydrochloride contents with time and date of dilution should be placed on the infusion solution container.


LIDOCAINE HYDROCHLORIDE AND DEXTROSE INJECTION (FOR CONTINUOUS INTRAVENOUS INFUSION) USP

Usual adult dose
Antiarrhythmic
Continuous intravenous infusion (usually following a loading dose), 1 to 4 mg per minute (20 to 50 mcg per kg of body weight per minute). {12}


Note: Infusion rates should be decreased in older patients and patients with congestive heart failure or hepatic dysfunction to avoid lidocaine toxicity. {12}


Usual adult prescribing limits
300 mg (about 4.5 mg per kg of body weight) in any one-hour period.

Usual pediatric dose
Antiarrhythmic
Continuous intravenous infusion (usually following a loading dose), 30 mcg (range, 20 to 50 mcg) (0.03 mg; range, 0.02 to 0.05 mg) of lidocaine hydrochloride per kg of body weight per minute. Rate of infusion should not exceed usual adult rate of 4 mg per minute.


Strength(s) usually available
U.S.—



Lidocaine Hydrochloride


0.1% w/v (1 mg per mL [250 mg per 250 mL, 500 mg per 500 mL, or 1 gram per 1000 mL]) (Rx)[Generic]


0.2% w/v (2 mg per mL [500 mg per 250 mL, 1 gram per 500 mL or 2 grams per 1000 mL]) (Rx)[Generic]


0.4% w/v (4 mg per mL [1 gram per 250 mL, 2 grams per 500 mL, or 4 grams per 1000 mL]) (Rx)[Generic]


0.8% w/v (8 mg per mL [2 grams per 250 mL, 4 grams per 500 mL, 8 grams per 1000 mL]) (Rx)[Generic]

Canada—



Lidocaine Hydrochloride


0.1% w/v (1 mg per mL [250 mg per 250 mL, 500 mg per 500 mL, or 1 gram per 1000 mL]) (Rx)[Generic]


0.2% w/v (2 mg per mL [500 mg per 250 mL, 1 gram per 500 mL, or 2 grams per 1000 mL]) (Rx)[Generic]


0.4% w/v (4 mg per mL [1 gram per 250 mL, 2 grams per 500 mL, or 4 grams per 1000 mL]) (Rx)[Generic]


0.8% w/v (8 mg per mL [2 grams per 250 mL or 4 grams per 500 mL]) (Rx)[Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F). Protect from freezing.



Revised: 01/13/2003



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Perry RS, Illsky SS. Basic cardiac electrophysiology and mechanisms of antiarrhythmic agents. Am J Hosp Pharm 1986 Apr; 43: 957-74.
  1. Sterile Lidocaine Hydrochloride USP powder package insert (IMS—US), 11/83.
  1. Xylocaine for ventricular arrhythmias package insert (Astra—US), 2/88.
  1. Xylocaine injection for ventricular arrhythmias package insert (Astra—US), Rev 5/89, Rec 5/92.
  1. Cusson J, Nattel S, Matthews C, et al. Age-dependent lidocaine disposition in patients with acute myocardial infarction. Clin Pharmacol Ther 1985; 37: 381-6.
  1. Berkowitz RL, Coustan DR, Mochizuki TK. Handbook for prescribing medications during pregnancy. 2nd ed. Boston/Toronto: Little, Brown and Company; 1986. p. 167.
  1. Mann LI, Bailey C, Carmichael A, Duchin S. Effect of lidocaine on fetal heart rate and fetal brain metabolism and function. Am J Obstet Gynecol 1972; 112(6): 789-93.
  1. Teramo K, Benowitz N, Heymann MA, et al. Effects of lidocaine on heart rate, blood pressure, and electrocorticogram in fetal sheep. Am J Obstet Gynecol 1974; 118(7): 935-49.
  1. Harrison DC. Current classification of antiarrhythmic drugs as a guide to their rational clinical use. Drugs 1986; 31: 93-5.
  1. Lidocaine hydrochloride in dextrose package insert (Baxter—US), Rev 4/89, Rec 6/93.
  1. Anderson JL. Current understanding of lidocaine as an antiarrhythmic agent: a review. Clin Ther 1984; 1986(2): 125-44.
  1. Ryan TJ, Antman EM, Brooks NH et al: ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). Available at http://www.acc.org/clinical/guidelines and http://www.americanheart.org. Accessed on 01/07/2003.

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