Propranolol and cimetidine may reduce clearance of lignocaine. Cardiac depressant effects of lignocaine are additive with beta blockers and antiarrhythmics. Besides, additive cardiac effects may occur when lignocaine is given with IV phenytoin.
Long-term use of phenytoin or other enzyme-inducers may increase dosage requirement of lignocaine. Acetazolamide, loop diuretics and thiazides produce hypokalaemia which antagonises effect of lignocaine.