Drug Interactions between landiolol 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 Patients being withdrawn from clonidine should be carefully monitored for blood pressure changes, severe headache, tremors, apprehension, flushing, nausea, and vomiting.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 CLOSELY: Concomitant use of landiolol and epinephrine may attenuate the response to epinephrine in the treatment of anaphylactic reactions. Some authorities suggest sensitivity and severity of allergic reactions, towards allergens, may be increased in patients taking beta-blockers alone and landiolol may reduce the response to usual doses of epinephrine. Additionally, epinephrine may reduce the therapeutic effects of landiolol. Coadministration with positive inotropes, vasoconstrictors, or sympathomimetic agents (e.g., epinephrine) may decrease landiolol's heart rate and blood pressure lowering effects.

MANAGEMENT : If coadministration is clinically necessary, careful titration of the landiolol infusion, dose adjustment of either agent to achieve the desired effect, and close hemodynamic monitoring are advised. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effect of beta-blockers. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure. Indomethacin and piroxicam have been reported to have greater attenuating effects than other NSAIDs, and indomethacin effects may be significant in patients with eclampsia.

MANAGEMENT: Patients receiving a beta-blocker who require prolonged (greater than 1 week) concomitant therapy with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of dosage of the NSAID. The interaction is not expected to occur with low doses (e.g., low-dose aspirin) or intermittent short-term administration of NSAIDs.