Drug Interactions between esmolol and silodosin

MONITOR: Additive hypotensive effects may occur when beta-blockers are used in combination with alpha-blockers. In the presence of beta-blockade, the risk and/or severity of first-dose effects associated with alpha-blockers such as postural hypotension and syncope may be increased. Beta-blockers may also blunt the reflex tachycardia that occurs in response to postural hypotension. In a study of eight normotensive male subjects, the lowest mean standing systolic blood pressure after 1 mg of oral prazosin was 88 mmHg, which was associated with a tachycardia of 117 bpm and an increase in mean plasma norepinephrine concentration. Concurrent administration of propranolol 80 mg or primidolol (a cardioselective beta-blocker) 100 mg increased the severity and duration of the postural hypotensive response, with lowest mean standing systolic blood pressure declining to 79 and 75 mmHg, respectively. Beta-blockade had no effect on the orthostatic release of norepinephrine, but attenuation of the postural tachycardia was observed. A similar exaggeration of first-dose response has been reported with prazosin administered in the presence of alprenolol. In another study, terazosin or placebo was given to nearly 100 patients with essential hypertension who had an inadequate response to atenolol 50 mg daily for eight weeks. After 10 weeks of coadministration, patients treated with terazosin (given at increasing daily dosages of 1, 2, 5, and up to 10 mg at two-week intervals) had significant mean decreases from baseline in supine blood pressure (systolic/diastolic = -8.8/-8.5 mmHg) and standing BP (-10.9/-9.5 mmHg), whereas the decreases in placebo-treated patients (supine, -2.3/-2.6 mmHg; standing, -1.4/-1.3 mmHg) were not significant. Terazosin produced similar effects in another study examining terazosin use against a background of hypotensive medications including beta-blockers. 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: Caution is advised during coadministration of these agents, particularly when initiating an alpha-blocker in the presence of a beta-blocker, including ophthalmic formulations. Small initial dosages of the alpha-blocker should be considered and gradually titrated to desired effect, while the systemic beta-blocker dosage may also need to be reduced. Hemodynamic responses should be monitored, especially during the first few weeks of therapy. Taking the alpha-blocker at bedtime may minimize the occurrence of orthostatic effects. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

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