Solifenacin succinate

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 0591-3795

Application: ANDA202551

Effective: 20231128

1 INDICATIONS AND USAGE Solifenacin succinate tablets are indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Solifenacin succinate tablets are a muscarinic antagonist indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency ( 1 ).

2 DOSAGE AND ADMINISTRATION 5 mg tablet taken orally once daily, and if well tolerated may be increased to 10 mg once daily ( 2.1 ). Do not exceed the 5 mg dose of solifenacin succinate tablets in patients with: Severe renal impairment creatinine clearance <30 mL/min/1.73 m 2 ( 2.2 , 8.6 ). Moderate hepatic impairment (Child-Pugh B). Solifenacin succinate tablets is not recommended in patients with severe hepatic impairment (Child-Pugh C) ( 2.3 , 8.7 ). Concomitant use of strong CYP3A4 inhibitors ( 2.4 , 7.1 ). 2.1 Dosing Information The recommended oral dose of solifenacin succinate tablets is 5 mg once daily. If the 5 mg dose is well tolerated, the dose may be increased to 10 mg once daily. Solifenacin succinate tablets should be taken with water and swallowed whole. Solifenacin succinate tablets can be administered with or without food. 2.2 Dosing Recommendations in Patients with Renal Impairment Do not exceed 5 mg once daily in patients with severe renal impairment (CL cr <30 mL/min/1.73 m 2 ) [see Use in Specific Populations ( 8.6 )] . 2.3 Dosing Recommendations in Patients with Hepatic Impairment Do not exceed 5 mg once daily in patients with moderate hepatic impairment (Child-Pugh B). Do not use solifenacin succinate tablets in patients with severe hepatic impairment (Child-Pugh C) [see Use in Specific Populations ( 8.7 )] . 2.4 Dosing Recommendations in Patients Taking CYP3A4 Inhibitors Do not exceed 5 mg once daily when solifenacin succinate tablets are administered with strong CYP3A4 inhibitors such as ketoconazole [see Drug Interactions ( 7.1 )] .

4 CONTRAINDICATIONS Solifenacin succinate tablets are contraindicated in patients: With urinary retention [see Warnings and Precautions ( 5.2 )] , With gastric retention [see Warnings and Precautions ( 5.3 )] , With uncontrolled narrow-angle glaucoma [see Warnings and Precautions ( 5.5 )] , and Who have demonstrated hypersensitivity to solifenacin succinate or the inactive ingredients in solifenacin succinate tablets. Reported adverse reactions have included anaphylaxis and angioedema [see Adverse Reactions ( 6.2 )] . Urinary retention ( 4 , 5.2 ). Gastric retention ( 4 , 5.3 ). Uncontrolled narrow-angle glaucoma ( 4 , 5.5 ). Hypersensitivity to this product or any of its components ( 4 , 5.1 , 6.2 ).

Not available.

6 ADVERSE REACTIONS The most common adverse reactions (>4% in solifenacin succinate-treated patients and > placebo-treated patients) were dry mouth and constipation at both 5 mg and 10 mg doses; and urinary tract infection and blurred vision at the 10 mg dose. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or 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 practice. Solifenacin succinate has been evaluated for safety in 1811 adult patients in four randomized, placebo-controlled trials (Studies 1 to 4) [see Clinical Studies ( 14 )] . Expected adverse reactions of antimuscarinic agents are dry mouth, constipation, blurred vision (accommodation abnormalities), urinary retention, and dry eyes. The incidence of dry mouth and constipation in patients treated with solifenacin succinate was higher in the 10 mg dose group compared to the 5 mg dose group. In the four 12-week double-blind clinical trials, severe fecal impaction, colonic obstruction, and intestinal obstruction were reported in one patient each, all in the solifenacin succinate 10 mg group. Angioneurotic edema was reported in one patient taking solifenacin succinate 5 mg. Compared to 12 weeks of treatment with solifenacin succinate, the incidence and severity of adverse reactions were similar in patients who remained on drug for up to 12 months in Study 5 [see Clinical Studies ( 14 )] . The most frequent adverse reaction leading to study discontinuation was dry mouth (1.5%). Table 1 lists the rates of identified adverse reactions, in the four randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with solifenacin succinate 5 or 10 mg once daily for up to 12 weeks. Table 1: Adverse Reactions Reported by ≥1% of Patients and Exceeding Placebo in Studies 1, 2, 3 and 4 Solifenacin Succinate Solifenacin Succinate P l acebo 5 mg 10 mg (%) (%) (%) Number of Patients 1216 578 1233 G ASTROINTESTINAL DISORDERS Dry Mouth 4.2 10.9 27.6 Constipation 2.9 5.4 13.4 Nausea 2.0 1.7 3.3 Dyspepsia 1.0 1.4 3.9 Abdominal Pain Upper 1.0 1.9 1.2 Vomiting NOS 0.9 0.2 1.1 I NFECTIONS AND INFESTATIONS Urinary Tract Infection NOS 2.8 2.8 4.8 Influenza 1.3 2.2 0.9 Pharyngitis NOS 1.0 0.3 1.1 NERVOUS SYSTEM DISORDERS Dizziness 1.8 1.9 1.8 E YE DISORDERS Vision Blurred 1.8 3.8 4.8 Dry Eyes NOS 0.6 0.3 1.6 RENAL AND URINARY DISORDERS Urinary Retention 0.6 0 1.4 G E NERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Edema Lower Limb 0.7 0.3 1.1 Fatigue 1.1 1.0 2.1 PSYCHIATRIC DISORDERS Depression NOS 0.8 1.2 0.8 RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS Cough 0.2 0.2 1.1 VASCULAR DISORDERS Hypertension NOS 0.6 1.4 0.5 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of solifenacin succinate in the U.S. and/or outside of the U.S. 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. General disorders and administration site conditions : peripheral edema, hypersensitivity reactions (including angioedema with airway obstruction, rash, pruritus, urticaria, anaphylactic reaction); Nervous system disorders : dizziness, headache, confusion, hallucinations, delirium, somnolence; Cardiac disorders : QT prolongation, Torsade de Pointes, atrial fibrillation, tachycardia, palpitations; Hepatobiliary disorders : liver disorders mostly characterized by abnormal liver function tests, AST (aspartate aminotransferase), ALT (alanine aminotransferase), GGT (gamma-glutamyl transferase); Renal and urinary disorders : renal impairment, urinary retention; Metabolism and nutrition disorders : decreased appetite, hyperkalemia; Skin and subcutaneous tissue disorders : exfoliative dermatitis, erythema multiforme, dry skin; Eye disorders : glaucoma; Gastrointestinal disorders : gastroesophageal reflux disease, ileus, vomiting, abdominal pain, dysgeusia, sialadenitis; Respiratory, thoracic and mediastinal disorders : dysphonia, nasal dryness; Musculoskeletal and connective tissue disorders : muscular weakness.