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Anti-arrhythmic drugs: Local anaesthetics of the amide type, such as lidocaine, should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide type local anaesthetics e.g. certain anti-arrhythmic drugs such as disopyramide, procainamide, mexilitene since potentiation of cardiac effects may occur. Specific interaction studies with lidocaine and anti-arrhythmic drugs class III (eg. amiodarone) have not been performed, but caution should be advised (see Precautions).
Amiodarone: Amiodarone has been reported to reduce the clearance of lidocaine in two case reports, although a small prospective study of combined therapy on lidocaine pharmacokinetics found no change in clearance or other pharmacokinetic factor. This combination has been reported to precipitate seizures and to lead to severe sinus bradycardia and a long sinoatrial arrest. Until more experience with concurrent use of lidocaine and amiodarone becomes available, patients receiving the combination should be monitored carefully.
Beta-adrenoreceptor antagonists: Propranolol and metoprolol reduce the metabolism of IV administered lidocaine and the possibility of this effect with other beta-adrenergic blockers should be kept in mind. If these drugs are administered concurrently, the patient should be closely observed for signs of lidocaine toxicity.
Cimetidine: Cimetidine reduces the clearance of IV administered lidocaine and toxic effects due to high serum lidocaine levels have been reported when these two drugs have been administered concurrently.
Anticonvulsive agents: Phenytoin and other antiepileptic drugs such as phenobarbitone, primidone and carbamazepine appear to enhance the metabolism of lidocaine but the significance of this effect is not known. Phenytoin and lidocaine have additive cardiac depressant effects.
Inhalational anaesthetics: Lidocaine decreases the minimum effective concentration of inhalational anaesthetics, e.g. nitrous oxide.
Skeletal muscle relaxants: Lidocaine and skeletal muscle relaxants, e.g. suxamethonium, lead to excessive neuromuscular blockade; therefore this combination must be used with caution.
Structurally related local anaesthetics: Lidocaine should be used with caution in patients receiving agents structurally related to local anaesthetics.
Patients that are administered local anaesthetics may be at increased risk of developing methaemoglobinaemia when concurrently exposed to the following oxidizing agents: Nitrates/Nitrites (eg. nitroglycerin, nitroprusside, nitric oxide, nitrous oxide); Local anaesthetics (eg. lidocaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, articaine); Antineoplastic agents (eg. cyclophosphamide, flutamide, rasburicase, isofamide, hydroxyurea); Antibiotics (eg. dapsone, sulphonamides, nitrofurantoin, para-aminosalicylic acid); Antimalarials (eg. chloroquine, primaquine); Anticonvulsants (eg. phenytoin, sodium valproate, phenobarbital); Other drugs (eg. acetaminophen, metoclopramide, sulfa drugs [i.e. sulfasalazine], quinine).
Laboratory effects: Creatinine: Creatinine measurements in patients with therapeutic plasma levels of lidocaine are about 15-35% higher when measured by an enzymatic method versus the Jaffé method. This appears to be due to assay interference from N-ethylglycine, a metabolite of lidocaine.
Creatine kinase: The intramuscular injection of lidocaine may result in an increase in creatine kinase levels for up to 48 hrs. This may interfere with the diagnosis of myocardial infarction.
