Source: Health Products and Food Branch (CA) Revision Year: 2021
Cathejell (lidocaine hydrochloride) is contraindicated in:
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 OVERDOSAGE).
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.
When using Cathejell in younger children, especially infants under the age of 3 months, care must be taken to ensure that the caregiver understands the need to limit the dose and area of application, and to prevent accidental ingestion (see DOSAGE AND ADMINISTRATION). Children should be closely observed during and after use of the lidocaine jelly, as they are at greater risk than adults for serious adverse events (e.g., methemoglobinemia).
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 firstpass 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 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.
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 (see also Part III: CONSUMER INFORMATION).
Cathejell is ineffective when applied to intact skin.
Lidocaine has been shown to be porphyrinogenic in animal models. Cathejell 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 porphyria patients.
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 amide-type local anesthetics.
Lidocaine should be used with caution in patients in severe shock.
Methemoglobinemia: Excessive dosage, or short intervals between doses, can result in sufficient high plasma levels of lidocaine or its metabolites to trigger methemoglobinemia. 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 methemoglobinemia should follow the established standard of care (see OVERDOSAGE).
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.
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 (see DOSAGE AND ADMISTRATION).
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.
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 (see ACTION AND CLINICAL PHARMACOLOGY). 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 hemodialysis patients (n=4) who received an intravenous dose of lidocaine. Therefore, renal impairment is not expected to significantly affect the pharmacokinetics of lidocaine when Cathejell is used for short treatment durations, according to dosage instructions (see DOSAGE AND ADMINISTRATION). Caution is recommended when lidocaine is used in patients with severely impaired renal function because lidocaine metabolites may accumulate during long term treatment (see DOSAGE AND ADMINISTRATION).
Lidocaine should be used with caution in persons with known drug sensitivities.
Cathejell is contraindicated in patients with known hypersensitivities to local anesthetics of the amide type and to other components in the formulation.
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.
Cathejell is contraindicated in patients with congenital or idiopathic methemoglobinemia and in infants 12 months of age or younger who require treatment with methemoglobin-inducing agents (see CONTRAINDICATIONS). Caution is advised for patients with glucose-6-phosphate dehydrogenase deficiency who are more susceptible to drug-induced methemoglobinemia (see CONTRAINDICATIONS).
There are no adequate and well-controlled studies in pregnant women on the effect of lidocaine on the developing fetus.
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.
Lidocaine is not contraindicated in labour and delivery. Should Cathejell be used concomitantly with other products containing lidocaine during labour and delivery, the total dose contributed by all formulations must be kept in mind.
Lidocaine and its metabolites are excreted in the breast milk. At therapeutic doses, the quantities of lidocaine and its metabolites in breast milk are small and generally are not expected to be a risk for the infant.
Children 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 (see DOSAGE AND ADMINISTRATION).
Cathejell is contraindicated for infants (12 months of age or younger) who require treatment with methemoglobin-inducing drugs (see CONTRAINDICATIONS).
Cathejell should be used with caution in children under the age of 2 as there are insufficient data to support the safety and efficacy of this product in this patient population at this time.
Children should be closely observed during and after use of topical anesthetics, as they are at greater risk than adults for serious adverse events (e.g., methemoglobinemia).
When using Cathejell in younger children, care must be taken to ensure that the caregiver understands the need to limit the dose and area of application, and to prevent accidental ingestion (see DOSAGE AND ADMINISTRATION).
Cathejell should not be applied to the genital mucosa of children or infants due to insufficient data on absorption.
Elderly patients may be more sensitive to systemic effects due to increased blood levels of lidocaine following repeated doses and may require dose reductions.
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 manifestations are excitatory and/or depressant and may be characterized by the following signs and symptoms of escalating severity: 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 (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 manifestations are usually depressant and are characterized by bradycardia, hypotension, arrhythmia, and cardiovascular collapse, which may lead to cardiac arrest.
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 (see DOSAGE FORMS, COMPOSITION, AND PACKAGING).
Lidocaine is mainly metabolized in the liver by CYP1A2 and CYP3A4 to its two major metabolites, monoethylglycinexylidine (MEGX) and glycinexylidine (GX), both of which are pharmacologically active. Lidocaine has a high hepatic extraction ratio. Only a small fraction (2%) of lidocaine is excreted unchanged in the urine. The hepatic clearance of lidocaine is expected to depend largely on blood flow.
Strong inhibitors of CYP1A2, such as fluvoxamine, given concomitantly with lidocaine, can cause a metabolic interaction leading to an increased lidocaine plasma concentration. Therefore, prolonged administration of lidocaine should be avoided in patients treated with strong inhibitors of CYP1A2, such as fluvoxamine. When co-administered with intravenous lidocaine, two strong inhibitors of CYP3A4, erythromycin and itraconazole, have each been shown to have a modest effect on the pharmacokinetics of intravenous lidocaine. Other drugs such as propranolol and cimetidine have been reported to reduce intravenous lidocaine clearance, probably through effects on hepatic blood flow and/or metabolism.
When lidocaine is used topically, plasma concentrations are of importance for safety reasons (see WARNINGS AND PRECAUTIONS, General; ADVERSE REACTIONS). However, with the low systemic exposure and short duration of topical application, the abovementioned metabolic drug-drug interactions are not expected to be of clinical significance when Cathejell is used according to dosage recommendations.
Clinically relevant pharmacodynamic drug interactions may occur with lidocaine and other local anesthetics or structurally related drugs, and Class I and Class III antiarrhythmic drugs due to additive effects.
Co-administration of Cathejell and other methemoglobin-inducing agents to patients 12 months of age or younger may result in clinical signs of methemoglobinemia (see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, ADVERSE REACTIONS).
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.
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.
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%.
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 coadministered with propranolol 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 longterm treatment with high doses of lidocaine.
Cathejell may induce the formation of methemoglobin and result in overt clinical signs of methemoglobinemia in patients treated concomitantly with Cathejell and other methemoglobin-inducing agents, including but not limited to sulfonamides, acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, para-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine and quinine (see CONTRAINDICATIONS and OVERDOSAGE).
Acetaminophen has been shown to induce methemoglobin formation in vitro and in animals. In humans, methemoglobin formation is very rare at therapeutic doses and overdoses of acetaminophen.
Interactions of lidocaine with food have not been established.
Interactions of lidocaine with herbal products have not been established.
Interactions of lidocaine with laboratory tests have not been established.
Interactions of lidocaine with lifestyle have not been established.
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