LIDOCAINE HYDROCHLORIDE- lidocaine hydrochloride injection, solution
McKesson Packaging Services Business Unit of McKesson Corporation
Lidocaine Hydrochloride Injection, USP is a sterile, nonpyrogenic solution of an antiarrhythmic agent administered intravenously by either direct injection or continuous infusion. It is available in various concentrations with the following characteristics:
(Total Lidocaine HCl)
For Direct Intravenous Injection
5 mL (100 mg)
6.0 (5.0 to 7.0)
5 mL (50 mg)
6.0 (5.0 to 7.0)
10 mL (1000 mg)
5.7 (5.0 to 7.0)
10 mL (2000 mg)
5.7 (5.0 to 7.0)
*1000 mg and 2000 mg concentrations FOR DILUTION ONLY.
Must not be administered without proper dilution prior to injection.
May contain sodium hydroxide and/or hydrochloric acid for pH adjustment. Injections containing 10 mg/mL (1%) contain sodium chloride 7 mg and injections containing 20 mg/mL (2%) lidocaine hydrochloride contain sodium chloride 6 mg to adjust tonicity. Single-dose solutions contain no preservative and unused portions must be discarded after use.
Lidocaine Hydrochloride, USP is chemically designated 2-(Diethylamino)-2’,6’-acetoxylidide monohydrochloride monohydrate, a white powder freely soluble in water. The molecular formula is C14 H22 N2 O• HCl •H2 O. The molecular weight is 288.82. It has the following structural formula:
The semi-rigid vial used for the plastic vials is fabricated from a specially formulated polyolefin. It is a copolymer of ethylene and propylene. The safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. The container requires no vapor barrier to maintain the proper drug concentration.
The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.
Mechanism of Action and Electrophysiology:
Studies of the effects of therapeutic concentrations of lidocaine on the electrophysiological properties of mammalian Purkinje fibers have shown that lidocaine attenuates phase 4 diastolic depolarization, decreases automaticity and causes a decrease or no change in excitability and membrane responsiveness. Action potential duration and effective refractory period of Purkinje fibers are decreased while the ratio of effective refractory period to action potential duration is increased. Action potential duration and effective refractory period of ventricular muscle are also decreased. Effective refractory period of the AV node may increase, decrease or remain unchanged and atrial effective refractory period is unchanged. Lidocaine raises the ventricular fibrillation threshold. No significant interactions between lidocaine and the autonomic nervous system have been described and consequently lidocaine has little or no effect on autonomic tone.
Clinical electrophysiological studies with lidocaine have demonstrated no change in sinus node recovery time or sinoatrial conduction time. AV nodal conduction time is unchanged or shortened and His-Purkinje conduction time is unchanged.
At therapeutic doses, lidocaine has minimal hemodynamic effects in normal subjects and in patients with heart disease. Lidocaine has been shown to cause no, or minimal decrease in ventricular contractility, cardiac output, arterial pressure or heart rate.
Pharmacokinetics and Metabolism:
Lidocaine is rapidly metabolized by the liver and less than 10% of a dose is excreted unchanged in the urine. Oxidative N-dealkylation, a major pathway of metabolism, results in the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological activities of these metabolites are similar to but less potent than lidocaine. The primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline.
The elimination half-life of lidocaine following an intravenous bolus injection is typically 1.5 to 2 hours. There are data that indicate that the half-life may be 3 hours or longer following infusions of greater than 24 hours.
Because of the rapid rate at which lidocaine is metabolized, any condition that alters liver function, including changes in liver blood flow, which could result from severe congestive heart failure or shock may alter lidocaine kinetics. The half-life may be two-fold or more greater in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics, but may increase the accumulation of metabolites.
Therapeutic effects of lidocaine are generally associated with plasma levels of 6 to 25 μmole/L (1.5 to 6 μg free base per mL). The blood to plasma distribution ratio is approximately 0.84. Objective adverse manifestations become increasingly apparent with increasing plasma levels above 6 μg free base per mL.
The plasma protein binding of lidocaine is dependent on drug concentration and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 μg free base per mL, 60 to 80 percent of lidocaine is protein bound. In addition to lidocaine concentration, the binding is dependent on the plasma concentration of the α-1-acid glycoprotein.
Lidocaine readily crosses the placental and blood-brain barriers. Dialysis has negligible effects on the kinetics of lidocaine.
Lidocaine hydrochloride injection administered intravenously or intramuscularly, is specifically indicated in the acute management of ventricular arrhythmias such as those occurring in relation to acute myocardial infarction, or during cardiac manipulation, such as cardiac surgery.
Lidocaine hydrochloride is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type. Lidocaine hydrochloride should not be used in patients with Stokes-Adams syndrome, Wolff-Parkinson-White syndrome or with severe degrees of sinoatrial, atrioventricular or intraventricular block in the absence of an artificial pacemaker.
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