Xylocaine Jelly (Lidocaine HCl)

XYLOCAINE® JELLY 2%

Astra

Lidocaine HCl

Topical Anesthetic

Action And Clinical Pharmacology: Mechanism of Action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Local anesthetics of the amide type are thought to act within the sodium channels of the nerve membrane.

Onset of Action: Anesthesia is achieved within 5 minutes, depending on the area of application. Duration of anesthesia is approximately 20 to 30 minutes. Lidocaine is ineffective when applied to intact skin.

Hemodynamics: Lidocaine, like other local anesthetics, may also have effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.

CNS toxicity (see Overdose: Symptoms and Treatment) usually precedes the cardiovascular effects since it occurs at lower plasma concentrations. Direct effects of local anesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.

Pharmacokinetics and Metabolism: The rate and extent of absorption depends upon concentration and total dose administered, the specific site of application and duration of exposure. In general, the rate of absorption of local anesthetic agents, following topical application to wound surfaces and mucous membranes is high, and occurs most rapidly after intratracheal and bronchial administration. The absorption of lidocaine jelly from the nasopharynx is usually lower than with other lidocaine products. Blood concentrations of lidocaine after instillation of the jelly in the intact urethra and bladder in doses up to 800 mg are fairly low and below toxic levels. Lidocaine is also well absorbed from the gastrointestinal tract, although little intact drug may appear in the circulation because of biotransformation in the liver.

Lidocaine readily crosses the placenta, and equilibrium in regard to free, unbound drug will be reached. Because the degree of plasma protein binding in the fetus is less than in the mother, the total plasma concentration will be greater in the mother, but the free concentrations will be the same.

Normally about 65% of the lidocaine is bound to plasma proteins. Amide local anesthetics are mainly bound to alpha-1-acid glycoprotein and also to albumin. Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine has a total plasma clearance of 0.95 L/min, a volume of distribution at steady state of 91 L, an elimination half-life of 1.6 h and an estimated hepatic extraction ratio of 0.65. The clearance of lidocaine is almost entirely due to liver metabolism, and depends both on liver blood flow and the activity of metabolizing enzymes.

The main elimination pathway of lidociane is by liver metabolism. The primary route of lidocaine is N-dealkylation to monoethylglycine xylidine (MEGX), followed by hydrolysis to 2,6-xylidine and hydroxylation to 4-hydroxy-2,6-xylidine. MEGX can also be further dealkylated to glycine xylidine (GX). The pharmacological/toxicological actions of MEGX and GX are similar to, but less potent than those of lidocaine. GX has a longer half-life (about 10 hours) than lidocaine and may accumulate during long-term administration. Approximately 90% of the lidocaine administered i.v. is excreted in the form of various metabolites, and less than 10% is excreted unchanged in the urine. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-xylidine, accounting for about 70 to 80% of the dose excreted in the urine.

The elimination half-life of lidocaine following an i.v. bolus injection is typically 1.5 to 2.0 hours. The elimination half-life in neonates (3.2 hours) is approximately twice that of adults. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.

Acidosis increases the systemic toxicity of lidocaine while the use of CNS depressants may increase the levels of lidocaine required to produce overt CNS effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 g free base per mL.

Indications And Clinical Uses: Surface anesthesia and lubrication for: The male and female urethra during cystoscopy, catheterization, exploration by sound and other endourethral operations. Nasal and pharyngeal cavities in endoscopic procedures such as gastroscopy and bronchoscopy. Proctoscopy and rectoscopy. Tracheal intubation.

Symptomatic treatment of pain in connection with cystitis and urethritis.

Contra-Indications: Known history of hypersensitivity to local anesthetics of the amide type or to other components in the formulation e.g., methylparaben, propylparaben (preservatives of the tube).

Manufacturers’ Warnings In Clinical States: Excessive dosage, or short intervals between doses, can result in high plasma levels of lidocaine or its metabolites and serious adverse effects. Absorption from the mucous membranes is variable but is especially high from the bronchial tree. Such applications may therefore result in rapidly rising or excessive plasma concentrations, with an increased risk for toxic symptoms, such as convulsions. Patients should be instructed to strictly adhere to the recommended dosage. This is especially important in children where doses vary with weight. The management of serious adverse reactions may require the use of resuscitative equipment, oxygen and other resuscitative drugs (see Overdose: Symptoms and Treatment).

Lidocaine should be used with caution in patients with sepsis and/or traumatized mucosa at the area of application, since under such conditions there is the potential for rapid systemic absorption.

When used for endotracheal tube lubrication, care should be taken to avoid introduction of the jelly into the lumen of the tube. If allowed into the inner lumen, the jelly may dry on the inner surface leaving a residue which tends to clump with flexion, narrowing the lumen. There have been rare reports in which this residue has caused the lumen to occlude. Similarly, do not use the jelly to lubricate the endotracheal stylettes.

Precautions: The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Absorption from mucous membranes is variable but especially high from the bronchial tree. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition. Lidocaine should also be used with caution in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired hepatic or renal function and in severe shock.

Because amide-type local anesthetics such as lidocaine are metabolized by the liver, these drugs, especially repeated doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations.

Lidocaine should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by these drugs.

Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. It has been shown that the use of amide local anesthetics in malignant hyperthermia patients is safe. However, there is no guarantee that neural blockade will prevent the development of malignant hyperthermia during surgery. It is also difficult to predict the need for supplemental general anesthesia. Therefore, a standard protocol for the management of malignant hyperthermia should be available.

Lidocaine should be used with caution in persons with known drug sensitivities. Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to lidocaine.

Drug Interactions: Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics, since the toxic effects are additive.

Pregnancy: It is reasonable to assume that a large number of pregnant women and women of childbearing age have been given lidocaine. No specific disturbances to the reproductive process have so far been reported, e.g., no increased incidence of malformations. However, care should be given during early pregnancy when maximum organogenesis takes place.

There are no adequate and well-controlled studies in pregnant women on the effect of lidocaine on the developing fetus.

Labor and Delivery: Lidocaine is not contraindicated in labor and delivery. Should Xylocaine Jelly 2% be used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind.

Lactation: Lidocaine is excreted in the breast milk, but in such small quantities that there is generally no risk of affecting the infant at therapeutic dose levels.

Adverse Reactions: Adverse experiences following the administration of lidocaine are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by overdosage or rapid absorption, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.

An increased incidence of postoperative sore throat has been reported following endotracheal tube lubrication with lidocaine jelly.

Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported: CNS: CNS manifestations are excitatory and/or depressant and may be characterized by circumoral paresthesia, lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, hyperacusis, tinnitus, blurred vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest.

Drowsiness following the administration of lidocaine is usually an early sign of a high lidocaine plasma level and may occur as a consequence of rapid absorption.

Cardiovascular: Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, arrhythmia and cardiovascular collapse, which may lead to cardiac arrest.

Allergic: Allergic reactions are characterized by cutaneous lesions, urticaria, edema or, in the most severe instances, anaphylactic shock. Allergic reactions of the amide type are rare and may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation.

Symptoms And Treatment Of Overdose: Acute systemic toxicity from local anesthetics is generally related to high plasma levels encountered during therapeutic use of local anesthetics and originates mainly in the central nervous and the cardiovascular systems (see Adverse Effects, Warnings and Precautions).Symptoms: CNS toxicity is a graded response, with symptoms and signs of escalating severity. The first symptoms are circumoral paresthesia, numbness of the tongue, lightheadedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors are more serious and precede the onset of generalized convulsions. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the increased muscular activity, together with the interference with normal respiration. In severe cases apnea may occur. Acidosis increases the toxic effects of local anesthetics.

Recovery is due to redistribution and metabolism of the local anesthetic drug. Recovery may be rapid unless large amounts of the drug have been administered.

Cardiovascular effects may be seen in cases with high systemic concentrations. Severe hypotension, bradycardia, arrhythmia and cardiovascular collapse may be the result in such cases.

Cardiovascular toxic effects are generally preceded by signs of toxicity in the CNS, unless the patient is receiving a general anesthetic or is heavily sedated with drugs such as a benzodiazepine or barbiturate.

Treatment: 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 administration. At the first sign of change, oxygen should be administered.

The first step in the management of systemic toxic reactions 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. This may prevent convulsions if they have not already occurred.

If necessary, use drugs to control convulsions. An anticonvulsant should be given i.v. if the convulsions do not stop spontaneously in 15 to 20 seconds. Thiopental 100 to 150 mg i.v. will abort the convulsions rapidly. Alternatively, diazepam 5 to 10 mg i.v. may be used, although its action is slower. Succinylcholine will stop the muscle convulsions rapidly, but will require tracheal intubation and controlled ventilation, and should only be used by those familiar with these procedures.

If cardiovascular depression is evident (hypotension, bradycardia), ephedrine 5 to 10 mg i.v. should be given and may be repeated, if necessary, after 2 to 3 minutes.

Should circulatory arrest occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance, since hypoxia and acidosis will increase the systemic toxicity of local anesthetics. Epinephrine (0.1 to 0.2 mg as i.v. or intracardial injections) should be given as soon as possible and repeated, if necessary.

Children should be given doses commensurate with their age and weight.

Dosage And Administration: When used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind. Debilitated, elderly and acutely ill patients should be given reduced doses.

Xylocaine Jelly in the plastic syringe is preservative-free, and intended for single use only. The tube presentation of Xylocaine Jelly contains preservatives. The syringe is graduated, i.e., a 3 mm line of jelly is equivalent to approximately 1 mL of jelly (20 mg lidocaine HCl).

Urethral Anesthesia: Surface Anesthesia of the Male Adult Urethra: For adequate analgesia in males, 20 mL (400 mg lidocaine HCl) jelly is usually required. The jelly is instilled slowly until the patient has a feeling of tension (approximately 10 mL) (200 mg). A penile clamp is then applied for several minutes at the corona, after which the rest of the jelly is instilled.

When anesthesia is especially important, e.g., during sounding or cystoscopy, a larger quantity of jelly (e.g., 30 to 40 mL) may be instilled in 3 to 4 portions and allowed to act for 10 to 12 minutes before insertion of the instrument. The jelly instilled into the bladder is also effective for procedures in this region.

To anesthetize only the anterior male urethra, e.g., for catheterization, small volumes (5 to 10 mL, i.e., 100 to 200 mg lidocaine HCl) are usually adequate for lubrication.

For Surface Anesthesia of the Female Adult Urethra: Instill 5 to 10 mL of jelly in small portions to fill the whole urethra. If desired, some jelly may be deposited on the orifice and covered with a cotton swab. In order to obtain adequate anesthesia, several minutes should be allowed prior to performing urological procedures.

Endoscopy: The instillation of 10 to 20 mL is recommended for adequate analgesia and a small amount may be applied to the lubricating instrument. When combined with other lidocaine products (e.g., for bronchoscopy), the total dose of lidocaine should not exceed 400 mg.

Lubrication for Endotracheal Intubation: Apply approximately 2 mL of jelly to the external surface of the endotracheal tube just prior to insertion. Care should be taken to avoid introducing the product into the lumen of the tube (see Warnings). Do not use the jelly to lubricate endotracheal stylettes. It is also recommended that the use of endotracheal tubes with dried jelly on the external surface be avoided for lack of lubricating effect.

Maximum Dosage: Adults: The dose depends on the application site. A safe dose for oral use is 400 mg (20 mL). A safe dose for use in the urethra and bladder is 800 mg (40 mL). A maximum single dosage is not established. No more than 4 doses should be given during a 24-hour period.

Children (under 12 years): It is difficult to recommend a maximum dose of any drug for children since this varies as a function of age and weight. The maximum amount per dose should not exceed 6 mg/kg of body weight or 3 mL per 10 kg weight. No more than 4 doses should be given during a 24-hour period.

Availability And Storage: Each mL of a clear to almost clear, slightly colored jelly contains: lidocaine HCl 20 mg. Nonmedicinal ingredients: hydroxypropyl methylcellulose, methyl- and propylparabens (30 mL tube only), sodium hydroxide and/or hydrochloric acid to adjust pH 6.0 to 7.0 and water for injection. Its water-miscible base, characterized by high viscosity and low surface tension, allows close and prolonged contact with mucous membrane. Prefilled single-use plastic syringe of 10 mL packaged in a Sterile Pack. Plastic tubes of 30 mL with 1 applicator cone. Store at 15 to 30°C. Protect from freezing.

Jelly Syringe: Instructions for Use: Screw plunger rod clockwise into grey rubber until rubber rotates; twist protective tab to break seal. The syringe is now ready for use.

XYLOCAINE® JELLY 2% Astra Lidocaine HCl Topical Anesthetic

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