Drug Interactions between Carduran and sildenafil

ADJUST DOSE: Sildenafil may potentiate the hypotensive effect of alpha blockers, resulting in symptomatic hypotension in some patients. Sildenafil 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 patients with benign prostatic hyperplasia stabilized on the alpha blocker doxazosin, coadministration of doxazosin (4 mg or 8 mg) and sildenafil (25 mg, 50 mg, or 100 mg) resulted in mean additional reductions of supine systolic and diastolic blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, respectively. Mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, respectively, were also observed. There were infrequent reports of patients experiencing symptomatic postural hypotension (dizziness, lightheadedness) 1 to 4 hours after dosing with doxazosin 50 or 100 mg. In a clinical study of healthy male subjects 45 to 78 years of age, administration of silodosin with a single 100 mg dose of sildenafil 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 sildenafil.

MANAGEMENT: Caution is advised if sildenafil 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 sildenafil. Therefore, patients should be stable on alpha blocker therapy prior to initiating sildenafil, and sildenafil should be initiated at the lowest recommended dosage when used for erectile dysfunction (i.e., 25 mg). No dosage adjustment is necessary if used in the treatment of pulmonary arterial hypertension. In those patients already on an optimized dosage of sildenafil, alpha blocker therapy should be initiated at the lowest dosage. The safety of sildenafil in combination with alpha blockers may be affected by other variables such as intravascular volume depletion and use of other antihypertensive medications.

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