Drug Interactions between carvedilol and epinephrine / lidocaine / tetracaine topical

MONITOR: Some beta-blockers may increase lidocaine levels and risk of toxicity. This interaction may also apply to topical formulations of lidocaine. The proposed mechanism is inhibition of CYP450 metabolism and/or decreased cardiac output and hepatic blood flow resulting in decreased hepatic metabolism of lidocaine. In addition, beta-blockers and lidocaine may also have additive negative inotropic effects on the heart. Data have been conflicting and variable. The degree of systemic absorption of topical lidocaine may be dependent on the duration of application and the applied surface area.

MANAGEMENT: Patients receiving concurrent therapy should be monitored for drowsiness, mental status changes, bradycardia, and hypotension. Lidocaine levels should be obtained when clinically necessary. If toxicity is suspected, the lidocaine infusion should be decreased, as possible or the topical formulation of lidocaine should be discontinued.

MONITOR: Coadministration of non-cardioselective beta-blockers, such as propranolol, with topical solutions containing epinephrine may enhance the hypertensive effect of epinephrine, which may increase the risk of cardiac arrest and hypertensive stroke. The mechanism of this interaction involves beta-blocker antagonism of epinephrine's beta-agonist effects which results in unopposed alpha-stimulated vasoconstriction and reflexive decreases in heart rate. Epinephrine vascular clearance may also be reduced by concomitant beta-blocker use. Following administration of intravenous, local, or subcutaneous epinephrine, patients receiving propranolol have experienced hypertensive reactions, including life-threatening reactions, and often accompanied by bradycardia and/or arrhythmias. Numerous clinical studies have demonstrated significant increases in blood pressure (i.e., 20 to 40 mmHg) and vascular resistance, and decreases in heart rate, in patients receiving non-cardioselective beta-blockers with epinephrine. There are numerous case reports of patients taking propranolol who developed severe hypertension after local infiltration of lidocaine mixed with epinephrine, including one patient who went into cardiac arrest. Theoretically, when a topical solution containing epinephrine is used with local anesthetics to provide pain relief for wound closure, it is possible for a sufficient amount of epinephrine to be absorbed through the skin, particularly via wounds or lacerations, to cause systemic effects; however data are lacking.

MANAGEMENT: Caution and close monitoring of cardiovascular status (i.e., blood pressure, heart rate) are recommended when topical solutions containing epinephrine are administered to patients treated with non-cardioselective beta-blockers. Some authorities recommend avoiding treatment with topical solutions containing epinephrine (AU; Laceraine Topical Wound Anaesthetic(R)) in patients receiving a non-cardioselective beta-blocker.