LIDOCAINE HYDROCHLORIDE AND DEXTROSE

Lidocaine Hydrochloride and 5% Dextrose Injection, USP is a sterile, nonpyrogenic solution prepared from lidocaine hydrochloride and dextrose in water for injection. It contains no antimicrobial agents. Lidocaine hydrochloride is designated chemically as 2-(Diethylamino) - 2', 6' - acetoxylidide monohydrochloride. The solution serves as a cardiac antiarrhythmic agent intended for intravenous use. Composition, osmolarity, pH and caloric content are shown in Table 1. The pH is adjusted with sodium hydroxide. Table 1 Composition Normal physiologic osmolarity range is approximately 280 to 310 mOsmol/L. Administration of substantially hypertonic solutions (≥ 600 mOsmol/L) may cause vein damage. Osmolarity (mOsmol/L) (calc) pH Caloric Content (kcal/L) **Lidocaine Hydrochloride, USP (mg/mL) ***Dextrose Hydrous, USP (g/L) 0.4% Lidocaine Hydrochloride and 5% Dextrose Injection, USP 4 50 282 4.0 (3.0 to 7.0) 170 0.8% Lidocaine Hydrochloride and 5% Dextrose Injection, USP 8 50 311 4.0 (3.0 to 7.0) 170 This VIAFLEX Plus plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). VIAFLEX Plus on the container indicates the presence of a drug additive in a drug vehicle. The VIAFLEX Plus plastic container system utilizes the same container as the VIAFLEX plastic container system. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million. However, the safety of the plastic has been confirmed in tests in animals according to USP biological standards for plastic containers as well as by tissue culture toxicity studies. Lidocaine Hydrochloride, USP and D-Glucose Monohydrate Structural Formula Images

Lidocaine hydrochloride administered intravenously is specifically indicated in the acute management of (1) ventricular arrhythmias occurring during cardiac manipulations, such as cardiac surgery and (2) life-threatening arrhythmias which are ventricular in origin, such as occur during acute myocardial infarction.

Therapy of ventricular arrhythmias is often initiated with a single IV bolus of 1.0 to 1.5 mg/kg at a rate of 25 to 50 mg/min. of lidocaine hydrochloride injection. Following acute treatment by bolus in patients in whom arrhythmias tend to recur and who are incapable of receiving oral antiarrhythmic agents, intravenous infusion of Lidocaine Hydrochloride and 5% Dextrose Injection, USP is administered continuously at the rate of 1 to 4 mg/min (0.020 to 0.050 mg/kg/min in the average 70 kg adult). The 0.4% solution (4 mg/mL) can be given at a rate of 15 to 60 mL/hr (0.25 to 1 mL/min). The 0.8% solution (8 mg/mL) can be given at a rate of 7.5 to 30 mL/hr (0.12 to 0.5 mL/min). Precise dosage regimen is determined by patient characteristics and response. Infusion rate should be reduced by approximately one-half to compensate for decreased rate of clearance after prolonged infusion (24 hours) (see Clinical Pharmacology ). Failure to adjust the rate of infusion in keeping with this altered ability to eliminate lidocaine may result in toxic accumulation of the drug in the patient’s serum. Intravenous infusions of lidocaine hydrochloride must be administered under constant ECG monitoring to avoid potential overdosage and toxicity. Intravenous infusion should be terminated as soon as the patient’s basic cardiac rhythm appears to be stable or at the earliest signs of toxicity (see OVERDOSAGE). It should rarely be necessary to continue intravenous infusions beyond 24 hours. As soon as possible and when indicated, patients should be changed to an oral antiarrhythmic agent for maintenance therapy. Caution: When administering lidocaine hydrochloride by continuous infusion, it is advisable to closely monitor the infusion rate. Administer Lidocaine Hydrochloride and 5% Dextrose Injection, USP only with a calibrated infusion device. Pediatric: Clinical studies to establish pediatric dosing schedules have not been conducted. The usual dosage is a bolus dose of 1 mg/kg followed by an infusion rate of 20 mcg to 50 mcg/kg/min. The bolus dose should be repeated if infusion is not initiated within 15 minutes of the initial bolus dose. Hepatic impairment is likely to decrease clearance and increase exposure level of lidocaine. Administer lidocaine at lower maintenance infusion rate with close monitoring of toxicity in patients with hepatic impairment. Renal Impairment : In patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), administer lidocaine at lower maintenance infusion rate with close monitoring of toxicity. Lidocaine is incompatible with the following due to precipitate formation (includes but is not limited to): • Amphotericin • Cephazolin sodium • Phenytoin sodium Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear, the seal is intact, and the container is undamaged. Some opacity of the container plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect solution quality or safety. The opacity will diminish gradually. Use of a final filter is recommended during administration of all parenteral solutions, where possible. Lidocaine must not be infused simultaneously through the same tubing with other medicinal products without first verifying their compatibility. Set the vent to the close position on a vented intravenous administration set to prevent air embolism. All injections in VIAFLEX Plus plastic containers are intended for intravenous administration using sterile equipment. Because dosages of this drug are titrated to response, no additives should be made to Lidocaine Hydrochloride and 5% Dextrose Injection, USP.

Hypersensitivity reactions, including anaphylactic reactions, have been reported with lidocaine. Lidocaine hydrochloride is contraindicated in patients with a history of hypersensitivity to local anesthetics of the amide type. Lidocaine is contraindicated in patients with Stokes-Adams syndrome, Wolff-Parkinson-White syndrome, or with severe degrees of sinoatrial, atrioventricular, or intraventricular block.

Systemic reactions of the following types have been reported: Nervous System Disorders: respiratory depression and arrest; unconsciousness; convulsions; tremors; twitching; vomiting; blurred or double vision; drowsiness; dizziness; light-headedness; tinnitus; sensation of heat, cold or numbness; euphoria; apprehension; agitation; confused state; paresthesia; dysarthria. Cardiovascular System: cardiovascular arrest; bradycardia which may lead to cardiac arrest; hypotension, Ventricular fibrillation, Ventricular tachycardia, Ventricular arrhythmia, Asystole. Gastrointestinal Disorders: Hypoesthesia oral, Nausea, Hematologic Effects: methemoglobinemia. Psychiatric Disorders: Disorientation Allergic reactions, including anaphylactic reactions, may occur but are infrequent. There have been no reports of cross sensitivity between lidocaine hydrochloride and procainamide or between lidocaine hydrochloride and quinidine.

Pharmacodynamics Interactions Digitalis derivatives: Monitor toxicity when lidocaine is used in patients with digitalis toxicity accompanied by supraventricular arrhythmia and/or atrioventricular block (see Contraindications ). When lidocaine is administered with other antiarrhythmic drugs such as amiodarone, phenytoin, procainamide, propranolol or quinidine, the cardiac effects may be additive or antagonistic and toxic effects may be additive. Pharmacokinetics Interactions Concomitant treatment with drugs which are inhibitors of CYP1A2 and/or CYP3A4 has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and thereby prolonging the elimination half-life. Monitor toxicity when administering lidocaine with CYP1A2 and/or CYP3A4 inhibitors. Concomitant use of lidocaine at steady-state concentrations of the CYP1A2 inhibitor fluvoxamine increases intravenous lidocaine plasma AUC and C max by 71% and 22%, and decreases MEGX AUC and C max by 54% and 65%. Fluvoxamine decreases the plasma clearance of lidocaine by 41%-60% and prolonged the mean half-life by one hour. Monitor toxicity when coadministering these medications. Concomitant use of lidocaine with propofol, a hypnotic agent and CYP3A4 inhibitor, may increase lidocaine plasma levels by reducing lidocaine clearance. Monitor toxicity when coadministering lidocaine with propofol. Concomitant treatment with drugs which are inducers of CYP1A2 and/or CYP3A4 (e.g., phenytoin) has the potential to decrease lidocaine plasma levels and higher doses may be required. Concomitant use of lidocaine with a weak CYP1A2 and CYP3A4 inhibitor has been reported to increase lidocaine plasma levels by 24% – 75% and may result in toxic accumulation of the drug. Monitor toxicity when coadministering lidocaine with cimetidine. Beta-adrenergic blockers (e.g. propranolol): Concomitant use of lidocaine with beta-adrenergic blockers may increase lidocaine plasma levels by decreasing hepatic blood flow and thereby decrease lidocaine clearance. Monitor for toxicity when coadministering lidocaine with drugs that decrease hepatic blood flow.