(Adults (>18 years of age

Rialocaine Gel 2% (lidocaine hydrochloride) is indicated for

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

(Geriatrics (> 65 years of age

Elderly patients should be given reduced doses commensurate with their age and physical condition

(Pediatrics (<18 years of age

Children should be given reduced doses commensurate with their age, weight and physical condition). Lidocaine should be used with caution in children younger than two years of age as there are insufficient data to support the safety and efficacy of this product in this patient population at this time

Dosing Considerations

General

When Rialocaine Gel 2% ( lidocaine hydrochloride ) is used concomitantly with other products containing lidocaine, the total dose contributed by all formulations must be kept in mind

The absorption of lidocaine gel from the nasopharynx is usually lower than with other lidocaine products. Blood concentrations of lidocaine after instillation of the gel in the intact urethra and bladder in doses up to 800 mg are fairly low and below toxic levels

Special Populations

Lidocaine should also be used with caution in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired hepatic or renal function and in severe shock

Debilitated patients, elderly patients, acutely ill patients, patients with sepsis, and children should be given reduced doses commensurate with their age, weight and physical condition

Rialocaine Gel 2% should be used with caution in children under the age of  2 as there is insufficient data to support the safety and efficacy of this product in this patient population at this time

Recommended Dose and Dosage Adjustment

Urethral Anesthesia

Surface Anesthesia of the Male Adult Urethra

For adequate analgesia in males, 20 mL (400 mg lidocaine hydrochloride) gel is usually required. The gel 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 gel is instilled

When anesthesia is especially important, e.g., during sounding or cystoscopy, a larger quantity of gel (e.g., 30-40 mL) may be instilled in 3-4 portions and allowed to act for 10-12 minutes before insertion of the instrument. The gel 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 (5-10 mL, i.e., 100-200 mg lidocaine HCl) are usually adequate for lubrication

For Surface Anesthesia of the Female Adult Urethra

Instill 5-10 mL of gel in small portions to fill the whole urethra. If desired, some gel 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 10-20 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

Proctoscopy and rectoscopy

Up to 20 mL can be used for anal and rectal procedures. The total dose should not exceed 400 mg lidocaine

Lubrication for Endotracheal Intubation

Apply approximately 2 mL of gel 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

Do not use the gel to lubricate endotracheal stylettes. It is also recommended that the use of endotracheal tubes with dried gel on the external surface be avoided for lack of lubricating effect

Maximum Dosage

Adults

The dose of Rialocaine Gel 2% 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 for Rialocaine Gel 2% is not established. No more than four 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 of Rialocaine Gel 2% should not exceed 6 mg/kg of body weight or 3 mL per 10 kg weight. No more than four doses should be given during a 24-hour period

For children over 12 years of age doses should be commensurate with weight and physical condition

General

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

The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Tolerance to elevated blood levels varies with the status of the patient

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

Rialocaine Gel 2% should be used with caution in children under the age of 2 as there is insufficient data to support the safety and efficacy of this product in this patient population at this time

In patients under general anesthesia who are paralyzed, higher plasma concentrations may occur than in spontaneously breathing patients. Unparalyzed patients are more likely to swallow a large proportion of the dose, which then undergoes considerable first-pass hepatic metabolism following absorption from the gut

Avoid contact with eyes

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

When used for endotracheal tube lubrication, care should be taken to avoid introduction of the Gel into the lumen of the tube. If allowed into the inner lumen, the gel 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 Gel to lubricate the endotracheal stylettes

When topical anesthetics are used in the mouth, the patient should be aware that the production of topical anesthesia may impair swallowing and thus enhance the danger of aspiration. Numbness of the tongue or buccal mucosa may enhance the danger of unintentional biting trauma. Food or chewing gum should not be taken while the mouth or throat area is anesthetized

Rialocaine Gel 2% is ineffective when applied to intact skin

Lidocaine has been shown to be porphyrinogenic in animal models

Rialocaine Gel 2% should only be prescribed to patients with acute porphyria on strong or urgent indications,

when they can be closely monitored. Appropriate precautions should be taken for all porphyric patients

Cardiovascular

Lidocaine should be used with caution in patients with bradycardia or impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by amid-type local anesthetics

Lidocaine should be used with caution in patients in severe shock

Hepatic

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

Neurologic

Epilepsy: The risk of central nervous system side effects when using lidocaine in patients with epilepsy is very low, provided that the dose recommendations are followed

Locomotion and Coordination: Topical lidocaine formulations generally result in low plasma concentrations because of a low degree of systemic absorption. However, depending on the dose, local anesthetics may have a very mild effect on mental function and coordination even in the absence of overt CNS toxicity and may temporarily impair locomotion and alertness

Renal

Lidocaine is metabolized primarily by the liver to monoethylglycinexylidine (MEGX, which has some CNS activity), and then further to metabolites glycinexylidine (GX) and 2,6-dimethylaniline. Only a small fraction

(2%) of lidocaine is excreted unchanged in the urine. The pharmacokinetics of lidocaine and its main metabolite were not altered significantly in haemodialysis patients (n=4) who received an intravenous dose of lidocaine. Therefore, renal impairment is not expected to significantly affect the pharmacokinetics of lidocaine when Lidocaine Gel 2% is used for short treatment durations, according to dosage instructions

Caution is recommended when lidocaine is used in patients with severely impaired renal function because lidocaine metabolites may accumulate during long term treatment

Sensitivity

Lidocaine should be used with caution in persons with known drug sensitivities

Lidocaine Gel 2% is contraindicated in patients with known hypersensitivities to local anesthetics of the amide type,or to other components in the formulation

Special Populations

Debilitated patients, acutely ill patients, and patients with sepsis should be given reduced doses commensurate with their age, weight and physical condition because they may be more sensitive to systemic effects due to increased blood levels of lidocaine following repeated doses

Carcinogenesis and Mutagenesis

Genotoxicity tests with lidocaine showed no evidence of mutagenic potential. A metabolite of lidocaine, 2,6-dimethylaniline, showed weak evidence of activity in some genotoxicity tests

A chronic oral toxicity study of the metabolite 2,6-dimethylaniline (0, 14, 45, 135 mg/kg) administered in feed to rats showed that there was a significantly greater incidence of nasal cavity tumors in male and female animals that had daily oral exposure to the highest dose of 2,6-dimethylaniline for 2 years. The lowest tumor-inducing dose tested in animals (135mg/kg) corresponds to approximately 50 times the amount of 2,6-dimethylaniline to which a

50 kg subject would be exposed following the application of 20 g of lidocaine gel 2% for 24 hours on the mucosa, assuming the highest theoretical extent of absorption of 100% and 80% conversion to 2,6-dimethylaniline. Based on a yearly exposure (once daily dosing with 2,6-dimethylaniline in animals and 5 treatment sessions with 20 g lidocaine gel 2% in humans), the safety margins would be approximately 3400 times when comparing the exposure in animals to man

Drug-Drug Interactions

Local anesthetics and agents structurally related to amide-type local anesthetics

Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to amide-type local anesthetics (e.g. antiarrhythmics such as mexiletine), since the toxic effects are additive

Antiarryhythmic Drugs

Class I Antiarrhythmic drugs

Class I antiarrhythmic drugs (such as mexiletine) should be used with caution since toxic effects are additive and potentially synergistic

Class III Antiarrhythmic drugs

Caution is advised when using Class III antiarrhythmic drugs concomitantly with lidocaine due to potential pharmacodynamic or pharmacokinetic interactions with lidocaine, or both. A drug interaction study has shown that the plasma concentration of lidocaine may be increased following administration of a therapeutic dose of intravenous lidocaine to patients treated with amiodarone (n=6). Case reports have described toxicity in patients treated concomitantly with lidocaine and amiodarone. Patients treated with Class III antiarrhythmic drugs (e.g.

amiodarone) should be kept under close surveillance and ECG monitoring should be considered, since cardiac effects of these drugs and lidocaine may be additive

Strong Inhibitors of CYP1A2 and CYP3A4

Cytochrome CYP1A2 and CYP3A4 are involved in the formation of the pharmacologically active lidocaine metabolite MEGX

Fluvoxamine: Strong inhibitors of CYP1A2, such as fluvoxamine, given during prolonged administration of lidocaine to areas with a high extent of systemic absorption (e.g., mucous membranes) can cause a metabolic interaction leading to an increased lidocaine plasma concentration. The plasma clearance of a single intravenous dose of lidocaine was reduced by 41 to 60% during co-administration of fluvoxamine, a selective and potent CYP1A2 inhibitor, to healthy volunteers

Erythromycin and Itraconazole: Erythromycin and itraconazole, which are strong inhibitors of CYP3A4, have been shown to reduce clearance of lidocaine by 9 to 18%, following a single intravenous dose of lidocaine to healthy volunteers

During combined co-administration with fluvoxamine and erythromycin the plasma clearance of lidocaine was reduced by 53%

β-blockers and cimetidine

Following a single intravenous dose of lidocaine, administered to healthy volunteers, the clearance of lidocaine has been reported to be reduced up to 47% when co-administered with propanolol and up to 30% when co-administered with cimetidine. Reduced clearance of lidocaine when co-administered with these drugs is probably due to reduced liver blood flow and/or inhibition of microsomal liver enzymes. The potential for clinically significant

interactions with these drugs should be considered during long-term treatment with high doses of lidocaine

Drug-Food Interactions

Interactions of lidocaine with food have not been established

Drug-Herb Interactions

Interactions of lidocaine with herbal products have not been established

Drug-Laboratory Tests Interactions

Interactions of lidocaine with laboratory tests have not been established

Drug-Lifestyle Interactions

Interactions of lidocaine with lifestyle have not been established

In common with other drugs, Lidocaine gel should not be used in early pregnancy unless the benefits outweigh the potential risks

No or negligible influence. Lidocaine administered parenterally may cause CNS stimulation, dizziness, nausea followed by depression and drowsiness

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 gel

Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported

Central Nervous System: CNS manifestations are excitatory and/or depressant and may be characterized by the following signs and symptoms of escalating severity: circumoral paresthesia, light-headedness, 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 (e.g., twitching, tremors, convulsions) 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 System: 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 (<0.1%) and may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation

Reporting of suspected adverse reactions 

- National Pharmacovigilance and Drug Safety Center (NPC)

• o Fax: +966-11-205-7662
• o To contact national Pharmacovigilance management: +966-11-2038222 ext.: 2353 – 2356 – 2317 – 2354 – 2334 – 2340
• o Toll-free: 8002490000
• o E-mail: npc.drug@sfda.gov.sa
• o Website: www.sfda.gov.sa/npc

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

It should be kept in mind that clinically relevant pharmacodynamics drug interactions (i.e., toxic effects) may occur with lidocaine and other local anesthetics or structurally related drugs, and Class I and Class III antiarrhythimic drugs due to additive effects

Symptoms

Central nervous system 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, hyperkalaemia, hypocalcaemia and hypoxia increase and extend 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 central nervous system, 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 convulsions occur, the objective of the treatment is to maintain ventilation and oxygenation and support circulation. Oxygen must be given and ventilation assisted if necessary (mask and bag or tracheal intubation) Should convulsions not stop spontaneously after 15-20 seconds, an anticonvulsant should be given iv to facilitate adequate ventilation and oxygenation. Thiopental sodium 1-3 mg/kg iv is the first choice. Alternatively diazepam 0.1 mg/kg bw iv may be used, although its action will be slow. Prolonged convulsions may jeopardise the patient's ventilation and oxygenation. If so, injection of a muscle relaxant (e.g.succinylcholine 1 mg/kg bw) will facilitate ventilation, and oxygenation can be controlled

Early endotracheal intubation is required when succinylcholine is used to control motor seizure activity

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

Should circulatory arrest occur, immediate cardiopulmonary resuscitation should be instituted

Continual 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 (0.1-0.2 mg as intravenous or intracardial injections) should be given as soon as possible and repeated, if necessary

Children should be given doses of epinephrine commensurate with their age and weight

Pharmacotherapeutic group: Anaesthetics Local. Amides. ATC code: NO1BB

Lidocaine is an amide local anaesthetic agent with a fast onset, blocking peripheral nervous conduction

Absorption: 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 gel from the nasopharynx is usually lower than with other lidocaine products. Blood concentrations of lidocaine after instillation of the gel 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

Distribution: Lidocaine has a total plasma clearance of 0.95 L/min and a volume of distribution at steady state of 91 L

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

The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 μg of free base per mL,60 to 80 percent of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein. Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion

Metabolism: Lidocaine is metabolized rapidly by the liver, and its metabolites and the unchanged drug are excreted by the kidneys. Biotransformation includes oxidative Ndealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. Only 2% of lidocaine is excreted unchanged. Most of it is metabolized first to monoethylglycinexylidide (MEGX) and then to glycinexylidide (GX) and 2,6-dimethylaniline. Up to 70% appears in the urine as 4-hydroxy- 2,6-dimethylaniline. The pharmacological/toxicological actions of MEGX and GX are similar to, but less potent than those of lidocaine. GX has a longer half-life (about10 h) than lidocaine and may accumulate during long-term administration

Excretion: Lidocaine has 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. Approximately 90% of the lidocaine administrated intravenously 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-dimethylaniline, accounting for about 70-80% of the dose excreted in the urine

The elimination half-life of lidocaine following an intravenous bolus injection is typically 1.5 to 2.0 hours. The elimination half-life in neonates (3.2 h) 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

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC

Glycerol

Hypromellose

Methyl hydroxybenzoate

Propyl hydroxybenzoate

Water for injection

None Known

Store below 30° C

Keep in the original container to protect from light

Once the pack has been opened , the content should be used within one month

Aluminium Tube with plastic screw cap

Apply using gauze or barrier gloves, if not available - wash hands after application