Silodosin - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Postural hypotension, with or without symptoms (e.g., dizziness), may develop when beginning silodosin capsules treatment.

In patients with moderate renal impairment, silodosin capsules dose should be reduced to 4 mg once daily.

Silodosin capsules should not be used in combination with other alpha-blockers.

Examine patients thought to have BPH prior to starting therapy with silodosin capsules to rule out the presence of carcinoma of the prostate.

Inform patients planning cataract surgery to notify their ophthalmologist that they are taking silodosin capsules because of the possibility of Intraoperative Floppy Iris Syndrome (IFIS).

5.1 Orthostatic Effects Postural hypotension, with or without symptoms (e.g., dizziness) may develop when beginning silodosin capsules treatment.

As with other alpha-blockers, there is potential for syncope.

Patients should be cautioned about driving, operating machinery, or performing hazardous tasks when initiating therapy [ see Adverse Reactions , Use in Specific Populations , Clinical Pharmacology , and Patient Counseling Information ].

5.2 Renal Impairment In a clinical pharmacology study, plasma concentrations (AUC and C max ) of silodosin were approximately three times higher in subjects with moderate renal impairment compared with subjects with normal renal function, while half-lives of silodosin doubled in duration.

The dose of silodosin capsules should be reduced to 4 mg in patients with moderate renal impairment.

Exercise caution and monitor such patients for adverse events [ see Use in Specific Populations and Clinical Pharmacology ] .

Silodosin capsules are contraindicated in patients with severe renal impairment [ see Contraindications ].

5.3 Hepatic Impairment Silodosin capsule has not been tested in patients with severe hepatic impairment, and therefore, should not be prescribed to such patients [ see Contraindications , Use in Specific Populations and Clinical Pharmacology ].

5.4 Pharmacokinetic Drug-Drug Interactions In a drug interaction study, co-administration of a single 8 mg dose of silodosin capsules with 400 mg ketoconazole, a strong CYP3A4 inhibitor, caused a 3.8-fold increase in maximum plasma silodosin concentrations and 3.2-fold increase in silodosin exposure (i.e., AUC).

Concomitant use of ketoconazole or other strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) is therefore contraindicated [ see Drug Interactions ].

5.5 Pharmacodynamic Drug-Drug Interactions The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined.

However, interactions may be expected, and silodosin capsules should not be used in combination with other alpha-blockers [ see Drug Interactions ].

A specific pharmacodynamic interaction study between silodosin and antihypertensive agents has not been performed.

However, patients in the Phase 3 clinical studies taking concomitant antihypertensive medications with silodosin capsules did not experience a significant increase in the incidence of syncope, dizziness, or orthostasis.

Nevertheless, exercise caution during concomitant use with antihypertensives and monitor patients for possible adverse events [ see Adverse Reactions and Drug Interactions ].

Caution is also advised when alpha-adrenergic blocking agents including silodosin capsules are co-administered with PDE5 inhibitors.

Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure.

Concomitant use of these two drug classes can potentially cause symptomatic hypotension [ see Drug Interactions ].

5.6 Carcinoma of the Prostate Carcinoma of the prostate and BPH cause many of the same symptoms.

These two diseases frequently co-exist.