The toxicity of lidocaine increases with its simultaneous use with cimetidine and propranolol due to increased lidocaine concentrations, this requires a reduction in the dose of lidocaine. Both drugs reduce hepatic blood flow. Besides, cimetidine inhibits microsomal activity. Ranitidine slightly reduces the clearance of lidocaine, which leads to an increase in its concentration. An increase in serum lidocaine concentration can also cause antiviral agents (for example, amprenavir, atazanavir, darunavir, lopinavir).
Hypokalemia caused by diuretics can reduce the effect of lidocaine when they are used together (see section "Special instructions").
Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally similar to local anesthetics of the amide type (eg, antiarrhythmics, such as mexiletine, tokainid), since systemic toxic effects are additive. Separate studies of drug interactions between lidocaine and class III antiarrhythmics (eg, amiodarone) have not been conducted, but caution is advisable.
In patients who are simultaneously receiving antipsychotics, lengthening or being able to extend the QT interval (eg, pimozide, sertindole, olanzapine, quetiapine, zotepin), prenylamine, epinephrine (with random intravenous administration) or antagonists of 5-HT3-serotonin receptors (for example, tropospheric, dolasetron), the risk of ventricular arrhythmias may increase.
Simultaneous use of quinupristin / dalfopristin may increase the concentration of lidocaine and thus increase the risk of ventricular arrhythmias; their simultaneous use should be avoided.
In patients simultaneously receiving muscle relaxants (eg, suxamethonium), the risk of an intensified and prolonged neuromuscular blockade may increase. After using bupivacaine in patients who received verapamil and timolol, reported on the development of cardiovascular failure; lidocaine is close to the structure of bupivacaine.
Dopamine and 5-hdroksitryptampp reduce the threshold of convulsive readiness for the clitoris. Opioids probably have a seizure effect, which is confirmed by the data that lidocaine reduces the convulsive threshold to fentanyl in humans.
The combination of opioids and antiemetics, sometimes used for sedation in children, can reduce the convulsive threshold to lidocaine and increase its inhibitory effect on the central nervous system.
The use of epinephrine with lidocaine can reduce systemic absorption, but with occasional intravenous administration, the risk of ventricular tachycardia and ventricular fibrillation increases dramatically.
Simultaneous use of other antiarrhythmics, (5-adrenergic blockers and blockers of "slow" calcium channels, can further reduce AV-induction, ventricular holding and contractility.
Simultaneous use of vasoconstrictor increases the duration of action of lidocaine.
Simultaneous use of lidocaine and ergot alkaloids (eg, ergotamine) can cause severe arterial hypotension.
Caution should be exercised when using sedatives, as they may affect the action of local anesthetics on the CNS.
Caution should be exercised with prolonged use of antiepileptic drugs (phenytoin), barbiturates and other inhibitors of microsomal liver enzymes, as this can lead to a decrease in efficacy and, as a result, increased demand for lidocaine.
On the other hand, intravenous administration of phenytoin can increase the inhibitory effect of lidocaine on the heart.
The analgesic effect of local anesthetics can be exacerbated by opioids and clonidine.
Ethyl alcohol, especially with prolonged abuse, can reduce the effect of local anesthetics.
Lidocaine is not compatible with amphotericin B, methohexiton and nitroglycerin. To mix lidocaine with other medicinal products is not recommended.