Source: Health Products and Food Branch (CA) Revision Year: 2021
XYLOCARD is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
XYLOCARD is contraindicated in patients:
This drug requires administration by experienced healthcare professionals.
Constant ECG monitoring is essential for the proper administration of XYLOCARD intravenously. Signs of excessive depression of cardiac conductivity, such as prolongation of PR interval and QRS complex, and the appearance of aggravation of arrhythmias, should be followed by prompt cessation of the intravenous infusion.
It is mandatory to have emergency resuscitative equipment and drugs immediately available to manage possible adverse reactions involving the cardiovascular, respiratory, or central nervous systems.
In emergency situations, when a ventricular rhythm disorder is suspected, and ECG equipment is not available, a single dose may be administered when the physician in attendance has determined that the potential benefits outweigh the possible risks. If possible, emergency resuscitative equipment and drugs should be available.
XYLOCARD should be used with caution in patients with:
Lower doses should be used in patients with congestive cardiac failure and following cardiac surgery.
Since CNS effects may not be apparent as an initial manifestation of toxicity, circulatory collapse should be monitored in unconscious patients.
Intravenous administration of XYLOCARD is sometimes accompanied by a hypotensive response, and, in overdosage, this may be precipitous. For this reason the intravenous dose should not exceed 100 mg in a single injection, and no more than 200-300 mg in a one hour period (see DOSAGE and ADMINISTRATION). When high doses are used and the patient’s myocardial function is impaired, combination with other drugs which reduce the excitability of cardiac muscle requires caution.
Repeated doses of XYLOCARD may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with their age and physical condition. XYLOCARD should also be used with caution in patients with epilepsy, impaired cardiac conduction, bradycardia, impaired hepatic function or renal function and in severe shock.
Long term studies in animals to evaluate the carcinogenic and mutagenic potential or the effect on fertility of lidocaine HCl have not been conducted.
Theoretical evidence suggests that lidocaine may have porphyrogenic properties. The clinical significance of this is unknown. Caution should be exercised if intravenous lidocaine (XYLOCARD) is administered to patients with acute porphyria.
Caution should be employed in the repeated use of XYLOCARD in patients with severe liver disease, since possible accumulation of lidocaine or its metabolites may lead to toxic phenomena.
Caution should be employed in the repeated use of XYLOCARD in patients with severe renal disease, since possible accumulation of lidocaine or its metabolites may lead to toxic phenomena.
Studies of lidocaine in animals to evaluate the effect on fertility have not been conducted.
Lidocaine crosses the placenta. Animal studies have revealed no evidence of harm to the fetus. Although lidocaine has been used extensively for surgical procedures during pregnancy with no reports of ill effects to mother or fetus, there are no adequate and well-controlled studies in pregnant women of the effects of lidocaine on the developing fetus. XYLOCARD should not be administered during pregnancy, particularly at early stage, unless the benefits are considered to outweigh the risks.
Lidocaine passes into breast milk. One case report calculated that breastmilk contained ~40% of the maternal serum concentration after two boluses and seven hours of infusion, potentially resulting in a dose up to ~1.5 mg of lidocaine per day in the infant. The amount of lidocaine appearing in breast milk from the nursing mother receiving parenteral lidocaine is therefore unlikely to lead a significant accumulation of the parent drug in the breast fed infant. The remote possibility of an idiosyncratic or allergic reaction in the breast fed infant from lidocaine remained to be determined.
A reduction in dosage may be necessary for elderly patients, particularly those with compromised cardiovascular and/or hepatic function and/or prolonged infusion. The doses should be adjusted individually to the patients' age and body weight. Dosages may need adaptation as cardiac output and hepatic blood flow decrease with advanced age indicating a decreased clearance of lidocaine
Use in patients with impaired hepatic function:
Patients with reduced hepatic blood flow or function have a longer lidocaine half-life and lower clearance and may therefore require a reduction in dosage.
Use in patients with impaired renal function:
Impairment of renal function is unlikely to affect lidocaine clearance in the short term (24 hours). However, toxicity due to accumulation of lidocaine and its metabolites may develop with prolonged or repeated administration.
Adverse experiences following the administration of lidocaine are similar in nature to those observed with other amide type agents. These adverse experiences are, in general, doserelated and may result from high plasma levels caused by excessive dosage or rapid absorption, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient.
Common adverse reactions are those from the central and peripheral nervous system. They occur in 5-10% of the patients and are mostly dose-related. The following definitions of frequencies are used: Very common (≥10%), common (1-9.9%), uncommon (0.1-0.9%), rare (0.01-0.09%) and very rare (<0.01%).
Systemic reactions of the following types have been reported from post-marketing data:
CNS manifestations are excitatory and/or depressant. Common adverse reactions are circumoral paresthesia, dizziness and drowsiness. Rare adverse reactions would include: persistent dizziness, lightheadedness, nervousness, apprehension, euphoria, confusion, hyperacusis, tinnitus, blurred vision, vomiting, and sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, apnea, 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.
Rare cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, asystole and cardiovascular collapse which may lead to cardiac arrest. Arrhythmias, including ventricular tachycardia/ventricular fibrillation have also been reported.
Very rarely, neonatal methaemoglobinaemia can occur (see WARNINGS AND PRECAUTIONS).
Allergic reactions are characterized by cutaneous lesions, urticaria, edema, or in the most severe and very rare instances, hypersensitivity including anaphylactic shock. Allergic reactions of the amide type are rare and may occur as a result of sensitivity either to the drug itself, or to other components of the formulation.
Idiosyncratic reactions have been reported at low doses in some patients. Cross-sensitivity between XYLOCARD and procainamide or XYLOCARD and quinidine have not been reported.
The drugs listed in this table are based on either drug interaction case reports or studies, or potential interactions due to the expected magnitude and seriousness of the interaction (i.e., those identified as contraindicated).
Lidocaine is mainly metabolized in the liver by CYP1A2 and CYP3A4 (see Pharmacokinetics). Since the affinity of lidocaine to CYP1A2 and CYP3A4 is very low compared to therapeutic plasma concentrations, it is less likely that the metabolism of substrates for these enzymes will be inhibited when coadministered with lidocaine. However, there is a potential for influence of other drugs on the plasma levels/effect of lidocaine, e.g. strong inhibitors or inducers of CYP1A2 and/or CYP3A4 and drugs that affect liver blood flow (see Table 3).
Table 3. Established or Potential Drug-Drug Interactions:
| Name | Reference | Effect | Clinical comment |
|---|---|---|---|
| Strong inhibitors of CYP1A2 (fluvoxamine) | CT | Coadministration of fluvoxamine reduced [41%] the elimination of lidocaine in healthy subjects. Given concomitantly with lidocaine, strong inhibitors of CYP1A2 can cause a metabolic interaction leading to increased lidocaine plasma concentrations. | Therefore, coadministration of lidocaine should be avoided in patients treated with strong inhibitors of CYP1A2, such as fluvoxamine. |
| CYP1A2 inducers (Phenytoin) | T | During concomitant administration of lidocaine and CYP1A2 inducers, plasma levels/effect of lidocaine may decrease. | Higher dose of lidocaine may be required. |
| Strong inhibitors of CYP3A4 (erythromycin, itraconazole) | CT | Erythromycin and itraconazole have each been shown to have a modest or no effect on the pharmacokinetics of intravenous lidocaine (0-18% decreased elimination with erythromycin but no effect with itraconazole). | No dose adjustment seems required. |
| CYP3A4 inducers (carbamazepine, phenobarbital, phenytoin, primidone) | CT | Concomitant administration with carbamazepine, phenobarbital, phenytoin, and primidone, may slightly decrease plasma levels of lidocaine (<10%). | No dose adjustment seems required. |
| Beta-blockers (propranolol, metoprolol, nadolol) | CT | Propranolol, metoprolol, and nadolol have been reported to reduce intravenous lidocaine clearance, probably through effects on hepatic blood flow and/or metabolism, and may increase the plasma concentration of lidocaine by about 30%, less with metoprolol. | Therefore concomitant administration of beta-blockers with lidocaine should be avoided. If not possible, close monitoring and dose adjustment may be required. |
| Cimetidine | CT | Cimetidine has an unspecific inhibitory effect on CYP (including CYP1A2 and CYP 3A4) mediated metabolism and reduces hepatic blood flow. Clinical experiments showed that the concomitant administration of cimetidine reduces the systemic clearance of lidocaine and increases lidocaine serum concentration by as much as 50%. Thus, therapeutic serum levels of lidocaine may rise to toxic levels when cimetidine is used concomitantly. Ranitidine has not displayed this effect. | Therefore, concomitant administration with lidocaine should be avoided. If not possible, close monitoring and dose adjustment of lidocaine and/or cimetidine may be required. |
| Amiodarone | CT, C | Like cimetidine, amiodarone has an unspecific inhibitory effect on CYP mediated metabolism. Concomitant administration has resulted in increased plasma levels of lidocaine and may result in toxic effects. | Therefore, concomitant administration with lidocaine should be avoided. If not possible, close monitoring and dose adjustment of lidocaine and/or amiodarone may be required. |
Legend: C = Case Study; CT = Clinical Trial; T = Theoretical
Interaction with food have not been established.
Interaction with herbal products have not been established.
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