Sodez Drug Interactions

Silodosin is metabolised extensively, mainly via CYP3A4, alcohol dehydrogenase and UGT2B7. Silodosin is also a substrate for P-glycoprotein. Substances that inhibit (such as ketoconazole, itraconazole, ritonaviror cyclosporine) or induce (such as rifampicin, barbiturates, carbamazepine, phenytoin) these enzymes and transporters may affect the plasma concentrations of silodosin and its active metabolite.
Alpha-blockers: There is inadequate information about the safe use of silodosin in association with other α-adrenoreceptor antagonists. Consequently, the concomitant use of other α-adrenoreceptor antagonists is not recommended.
CYP3A4 inhibitors: In an interaction study, a 3.7-fold increase in maximum silodosin plasma concentrations and a 3.1 fold increase in silodosin exposure (i.e. AUC) were observed with concurrent administration of a potent CYP3A4 inhibitor (ketoconazole 400 mg). Concomitant use with potent CYP3A4 inhibitors (such as ketoconazole, itraconazole, ritonavir or cyclosporine) is not recommended.
When silodosin was co-administered with a CYP3A4 inhibitor of moderate potency such as diltiazem, an increase in silodosin AUC of approximately 30% was observed, but C_max and half-life were not affected.
This change is clinically not relevant and no dose adjustment is required.
PDE-5 inhibitors: Minimal pharmacodynamic interactions have been observed between silodosin and maximum doses of sildenafil or tadalafil. In a placebo-controlled study in 24 subjects 45-78 years of age receiving silodosin, the co-administration of sildenafil 100 mg or tadalafil 20 mg induced no clinically meaningful mean decreases in systolic or diastolic blood pressure, as assessed by orthostatic tests (standing versus supine). In the subjects over 65 years, the mean decreases at the various time points were between 5 and 15 mmHg (systolic) and 0 and 10 mmHg (diastolic). Positive orthostatic tests were only slightly more common during co-administration; however, no symptomatic orthostasis or dizziness occurred. Patients taking PDE-5 inhibitors concomitantly with silodosin should be monitored for possible adverse reactions.
Antihypertensives: In the clinical study program, many patients were on concomitant antihypertensive therapy (mostly agents acting on the renin-angiotensin system, beta-blockers, calcium antagonists and diuretics) without experiencing an increase in the incidence of orthostatic hypotension. Nevertheless, caution should be exercised when starting concomitant use with antihypertensives and patients should be monitored for possible adverse reactions.
Digoxin: Steady state levels of digoxin, a substrate of P-glycoprotein, were not significantly affected by co-administration with silodosin 8 mg once daily. No dose adjustment is required.