Drug Interactions between levobetaxolol ophthalmic and R.E.C.K.

MONITOR CLOSELY: Clonidine and beta-blockers may have synergistic pharmacodynamic effects resulting in marked AV block, bradycardia, and hypotension. Conversely, cases of antagonism of hypotensive effects have been reported, the mechanism of which is unknown. In addition, potentiation of the hypertensive rebound associated with abrupt withdrawal of clonidine or both clonidine and the beta blocker may occur. Increased blood pressure, hypertensive crisis, hypertensive encephalopathy, strokes, and fatalities have been reported after clonidine withdrawal. The proposed mechanism is related to increased catecholamine release after clonidine withdrawal, and concurrent beta-blockade results in unopposed alpha-adrenergic effects of the catecholamines, resulting in vasoconstriction. Patients who discontinue clonidine while taking noncardioselective beta blockers appear to be at a higher risk of developing rebound hypertension.

MANAGEMENT: Close monitoring of blood pressure is recommended for patients receiving this combination. Patients should be advised to notify their doctor if they experience a reduced heart rate, dizziness, fainting, or headaches. Clonidine should never be discontinued abruptly, but should be tapered off over 2 to 4 days. The beta blocker should be discontinued a few days before gradually discontinuing the clonidine. It has also been suggested that replacing clonidine and the beta blocker with labetalol (an alpha and beta blocker) may prevent rebound hypertension although some symptoms from increased catecholamine levels occur, or selecting a cardioselective beta blocker (e.g. atenolol, betaxolol, bisoprolol, metoprolol) which is theoretically not expected to exacerbate the pressor response. Patients being withdrawn from clonidine should be carefully monitored for blood pressure changes, severe headache, tremors, apprehension, flushing, nausea, and vomiting.

MONITOR: Beta-blockers may antagonize the cardiostimulatory effects of pressor agents by blocking beta-1 adrenergic receptors in the heart. Vasopressors may be less effective if the patient is receiving, or has recently received, a beta-blocking drug. In addition, peripheral vascular resistance may increase due to unopposed alpha-adrenergic effects of pressor agents in the presence of beta-blockade. Theoretically, the interaction may also occur with beta-blocker ophthalmic preparations, since they may be systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

MANAGEMENT: No specific intervention is necessary, but clinicians should be alert to the potential for diminished cardiac response when pressor agents are used in patients treated with beta-blockers, including ophthalmic formulations. A beta-blocker such as propranolol may be used to treat cardiac arrhythmias that occur during administration of pressor agents like mephentermine, metaraminol, norepinephrine, or phenylephrine.