Ureleve Special Precautions

Orthostatic Effects: Postural hypotension, with or without symptoms (e.g., dizziness) may develop when beginning Silodosin 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.
Pharmacokinetic Drug-Drug Interactions: In a drug interaction study, co-administration of a single 8 mg dose of Silodosin 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.
Pharmacodynamic Drug-Drug Interactions: The pharmacodynamic interactions between silodosin and other alpha-blockers have not been determined. However, interactions may be expected, and Silodosin should not be used in combination with other alpha-blockers.
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 did not experience a significant increase in the incidence of syncope, dizziness, or orthostasis. Nevertheless, exercise caution during concomitant use with antihypertensive and monitor patients for possible adverse events.
Caution is also advised when alpha-adrenergic blocking agents including Silodosin 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.
Carcinoma of the Prostate: Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently co-exist. Therefore, patients thought to have BPH should be examined prior to starting therapy with Silodosin to rule out the presence of carcinoma of the prostate.
Intraoperative Floppy Iris Syndrome: Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients on alpha-1 blockers or previously treated with alpha-1 blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents; progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs; and potential prolapse of the iris toward the phacoemulsification incisions. Patients planning cataract surgery should be told to inform their ophthalmologist that they are taking Silodosin.
Laboratory Test Interactions: No laboratory test interactions were observed during clinical evaluations. Treatment with Silodosin for up to 52 weeks had no significant effect on prostate-specific antigen (PSA).
Effects on Ability to Drive and Use Machines: One of the adverse effects is dizziness; patients are advised to refrain from driving and operating machinery.
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 should be reduced to 4 mg in patients with moderate renal impairment. Exercise caution and monitor such patients for adverse events. Silodosin is contraindicated in patients with severe renal impairment.
The effect of renal impairment on Silodosin pharmacokinetics was evaluated in a single dose study of six male patients with moderate renal impairment and seven male subjects with normal renal function. Plasma concentrations of Silodosin were approximately three times higher in subjects with moderate renal impairment compared with subjects with normal renal function.
Silodosin should be reduced to 4 mg per day in patients with moderate renal impairment. Exercise caution and monitor patients for adverse events.
Silodosin has not been studied in patients with severe renal impairment. Silodosin is contraindicated in patients with severe renal impairment.
Hepatic Impairment: Silodosin has not been tested in patients with severe hepatic impairment, and therefore, should not be prescribed to such patients.
In a study comparing nine male patients with moderate hepatic impairment (Child-Pugh scores 7 to 9), to nine healthy male subjects, the single dose pharmacokinetics of Silodosin were not significantly altered in patients with hepatic impairment. No dosing adjustment is required in patients with mild or moderate hepatic impairment.
Silodosin has not been studied in patients with severe hepatic impairment. Silodosin is contraindicated in patients with severe hepatic impairment.
Use in Pregnancy: See Use in Pregnancy & Lactation section for further information.
Use in Children: Silodosin is not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established.
Use in the Elderly: In double-blind, placebo-controlled, 12-week clinical studies of Silodosin, 259 (55.6%) were under 65 years of age, 207 (44.4%) patients were 65 years of age and over, while 60 (12.9%) patients were 75 years of age and over. Orthostatic hypotension was reported in 2.3% of Silodosin patients <65 years of age (1.2% for placebo), 2.9% of Silodosin patients ≥65 years of age (1.9% for placebo), and 5.0% of patients ≥75 years of age (0% for placebo). There were otherwise no significant differences in safety or effectiveness between older and younger patients.