Silodosin

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 46708-405

Application: ANDA211731

Effective: 20230130

1 INDICATIONS AND USAGE Silodosin capsule, a selective alpha-1 adrenergic receptor antagonist, is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) [ see Clinical Studies (14 )]. Silodosin capsule is not indicated for the treatment of hypertension. Silodosin capsule, an alpha-1 adrenergic receptor antagonist, is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). (1) Silodosin capsule is not indicated for the treatment of hypertension.

2 DOSAGE AND ADMINISTRATION 8 mg capsules taken orally once daily with a meal. (2.1) 4 mg capsules taken orally once daily with a meal for those with moderate renal impairment [Creatinine Clearance (CCr) 30 to 50 mL/min]. (2.2) 2.1 Dosing Information The recommended dose is 8 mg orally once daily with a meal. Patients who have difficulty swallowing pills and capsules may carefully open the silodosin capsule and sprinkle the powder inside on a tablespoonful of applesauce. The applesauce should be swallowed immediately (within 5 minutes) without chewing and followed with an 8 oz glass of cool water to ensure complete swallowing of the powder. The applesauce used should not be hot, and it should be soft enough to be swallowed without chewing. Any powder/applesauce mixture should be used immediately (within 5 minutes) and not stored for future use. Subdividing the contents of a silodosin capsule is not recommended [ see Clinical Pharmacology (12.3 )]. 2.2 Dosage Adjustment in Special Populations Renal impairment: Silodosin capsule is contraindicated in patients with severe renal impairment (CCr <30 mL/min). In patients with moderate renal impairment (CCr 30 to 50 mL/min), the dose should be reduced to 4 mg once daily taken with a meal. No dosage adjustment is needed in patients with mild renal impairment (CCr 50 to 80 mL/min) [ see Contraindications (4), Warnings and Precautions (5.2), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3 )]. Hepatic impairment: Silodosin capsule has not been studied in patients with severe hepatic impairment (Child-Pugh score ≥10) and is therefore contraindicated in these patients. No dosage adjustment is needed in patients with mild or moderate hepatic impairment [ see Contraindications (4), Warnings and Precautions (5.3), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3 )].

4 CONTRAINDICATIONS Severe renal impairment (CCr <30 mL/min) Severe hepatic impairment (Child-Pugh score ≥10) Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) [ see Drug Interactions (7.1) ] Patients with a history of hypersensitivity to silodosin or any of the ingredients of silodosin capsules [ see Adverse Reactions (6.2) and Description (11) ] Patients with severe renal impairment [Creatinine Clearance (CCr <30 mL/min)]. (4) Patients with severe hepatic impairment (Child-Pugh score ≥ 10). (4) Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir). (4) Patients with a history of hypersensitivity to silodosin or any of the ingredients of silodosin capsules. (4)

Not available.

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥2%) are retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion. (6) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In U.S. clinical trials, 897 patients with BPH were exposed to 8 mg silodosin capsules daily. This includes 486 patients exposed for 6 months and 168 patients exposed for 1 year. The population was 44 to 87 years of age, and predominantly Caucasian. Of these patients, 42.8% were 65 years of age or older and 10.7% were 75 years of age or older. In double-blind, placebo controlled, 12-week clinical trials, 466 patients were administered silodosin capsules and 457 patients were administered placebo. At least one treatment-emergent adverse reaction was reported by 55.2% of silodosin capsules treated patients (36.8% for placebo treated). The majority (72.1%) of adverse reactions for the silodosin capsules treated patients (59.8% for placebo treated) were qualified by the investigator as mild. A total of 6.4% of silodosin capsules treated patients (2.2% for placebo treated) discontinued therapy due to an adverse reaction (treatment-emergent), the most common reaction being retrograde ejaculation (2.8%) for silodosin capsules treated patients. Retrograde ejaculation is reversible upon discontinuation of treatment. Adverse Reactions observed in at least 2% of patients: The incidence of treatment-emergent adverse reactions listed in the following table were derived from two 12-week, multicenter, double-blind, placebo-controlled clinical studies of silodosin capsules 8 mg daily in BPH patients. Adverse reactions that occurred in at least 2% of patients treated with silodosin capsules and more frequently than with placebo are shown in Table 1. Table 1: Adverse Reactions Occurring in ≥2% of Patients in 12-week, Placebo-Controlled Clinical Trials Adverse Reactions Silodosin Capsules N = 466 n (%) Placebo N = 457 n (%) Retrograde Ejaculation 131 (28.1) 4 (0.9) Dizziness 15 (3.2) 5 (1.1) Diarrhea 12 (2.6) 6 (1.3) Orthostatic Hypotension 12 (2.6) 7 (1.5) Headache 11 (2.4) 4 (0.9) Nasopharyngitis 11 (2.4) 10 (2.2) Nasal Congestion 10 (2.1) 1 (0.2) In the two 12-week, placebo-controlled clinical trials, the following adverse events were reported by between 1% and 2% of patients receiving silodosin capsules and occurred more frequently than with placebo: insomnia, PSA increased, sinusitis, abdominal pain, asthenia, and rhinorrhea. One case of syncope in a patient taking prazosin concomitantly and one case of priapism were reported in the silodosin capsules treatment group. In a 9-month open-label safety study of silodosin capsules, one case of Intraoperative Floppy Iris Syndrome (IFIS) was reported. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of silodosin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Skin and subcutaneous tissue disorders: toxic skin eruption, purpura, skin rash, pruritus and urticaria Hepatobiliary disorders: jaundice, impaired hepatic function associated with increased transaminase values Immune system disorders: allergic-type reactions, not limited to skin reactions including swollen tongue and pharyngeal edema resulting in serious outcomes.