Drug Interactions between Cialis and polythiazide / prazosin

MONITOR: The hypotensive effects of thiazide diuretics and alpha-adrenergic blockers may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Patients should be advised to take the alpha-blocker at bedtime and to notify their physician if they experience dizziness or syncope while awake.

ADJUST DOSE: Tadalafil may potentiate the hypotensive effect of alpha blockers, resulting in symptomatic hypotension in some patients. Tadalafil inhibits phosphodiesterase-5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can cause peripheral vasodilation that may be additive with that induced by alpha blockers. In 18 healthy subjects taking doxazosin 8 mg daily for at least 7 days, administration of tadalafil 20 mg resulted in significant augmentation of the blood pressure lowering effect of doxazosin, an alpha-1 adrenergic blocker. Specifically, nine patients given tadalafil had either a standing systolic blood pressure of less than 85 mm Hg or a decrease from baseline of greater than 30 mm Hg at one or more time points, compared to three such patients when given placebo. Two significant adverse events (vertigo and dizziness) potentially related to blood pressure effects were reported with tadalafil, compared to none with placebo. No syncope was reported. In a clinical study of healthy male subjects 45 to 78 years of age, administration of silodosin with a single 20 mg dose of tadalafil resulted in increased frequency of positive orthostatic test results during a 12-hour period following concomitant dosing compared to administration with placebo. No events of symptomatic orthostasis or dizziness were reported in subjects receiving silodosin with tadalafil, a selective alpha-1A adrenergic blocker. No significant adverse events related to decreases in blood pressure were observed when a single dose of tadalafil 10 mg or 20 mg was administered to healthy subjects taking 0.4 mg once-daily tamsulosin, another selective alpha-1A adrenergic blocker.

MANAGEMENT: Caution is advised if tadalafil is used in combination with alpha blockers. Patients who demonstrate hemodynamic instability on alpha blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of tadalafil. Therefore, patients should be stable on alpha blocker therapy prior to initiating tadalafil, and tadalafil should be initiated at the lowest recommended dosage. In those patients already on an optimized dosage of tadalafil, alpha blocker therapy should be initiated at the lowest dosage. Clinicians should bear in mind that the safety of tadalafil in combination with alpha blockers may also be affected by other variables such as intravascular volume depletion and use of other antihypertensive medications. The combination of tadalafil and alpha blockers is not recommended for the treatment of benign prostatic hyperplasia (BPH) due to the lack of safety and efficacy data. Patients on alpha blocker therapy for BPH should discontinue the alpha blocker at least one day prior to starting tadalafil for once-daily use in the treatment of BPH.

Based on their pharmacology, phosphodiesterase-5 (PDE5) inhibitors may conceivably potentiate the hypotensive effect of antihypertensive medications or effects of agents with hypotensive properties. These agents inhibit PDE5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can cause peripheral vasodilation. However, clinical pharmacology studies of tadalafil (administered as a 10 mg dose except in studies with angiotensin II receptor (AR) blockers and amlodipine, which used a dose of 20 mg) have demonstrated no clinically significant interaction with various antihypertensive drugs from major classes including calcium channel blockers, ACE inhibitors, beta blockers, thiazide diuretics, and AR blockers. Tadalafil 10 mg and 20 mg also had no clinically significant effect on blood pressure changes due to tamsulosin, an alpha-1a blocker. In addition, analysis of data from Phase 3 clinical trials showed no difference in adverse events in patients taking tadalafil with or without antihypertensive medications. In patients receiving concomitant antihypertensive medications, tadalafil 20 mg may induce a blood pressure decrease that is, in general, minor and not likely to be clinically relevant. In a clinical study of healthy male subjects 45 to 78 years of age, administration of silodosin with a single 20 mg dose of tadalafil resulted in increased frequency of positive orthostatic test results during a 12-hour period following concomitant dosing compared to administration with placebo. No events of symptomatic orthostasis or dizziness were reported in subjects receiving silodosin with tadalafil. Nevertheless, patients should be advised of the potential for interaction and to contact their doctor if they experience symptoms of hypotension such as dizziness, lightheadedness, or fainting.