Solifenacin Succinate (Page 2 of 6)

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, and anaphylactic reaction);

Nervous system disorders: dizziness, headache, confusion, hallucinations, delirium, and 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.

7 DRUG INTERACTIONS

7.1 Strong CYP3A4 Inhibitors

Solifenacin is a substrate of CYP3A4. Concomitant use of ketoconazole, a strong CYP3A4 inhibitor, significantly increased the exposure of solifenacin [see Clinical Pharmacology ( 12.3)]. The dosage of solifenacin succinate tablets greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors [see Dosage and Administration ( 2.4)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no studies with the use of solifenacin succinate in pregnant women to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. No adverse developmental outcomes were observed in animal reproduction studies with oral administration of solifenacin succinate to pregnant mice during the period of organogenesis at a dose resulting in 1.2 times the systemic exposure at the maximum recommended human dose (MRHD) of 10 mg/day. However, administration of doses 3.6 times and greater than the MRHD during organogenesis produced maternal toxicity in the pregnant mice and resulted in developmental toxicity and reduced fetal body weights in offspring [see Data ].

In the U.S. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

Oral administration of14 C-solifenacin succinate to pregnant mice resulted in the recovery of radiolabel in the fetus indicating that solifenacin-related product can cross the placental barrier. In pregnant mice, administration of solifenacin succinate at a dose of 250 mg/kg/day (7.9 times the systemic exposure at the MRHD of 10 mg), resulted in an increased incidence of cleft palate and increased maternal lethality. Administration of solifenacin succinate to pregnant mice during organogenesis at greater than or equal to 3.6 times (100 mg/kg/day and greater) the systemic exposure at the MRHD, resulted in reduced fetal body weights and reduced maternal body weight gain. No embryo-fetal toxicity or teratogenicity was observed in fetuses from pregnant mice treated with solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the MRHD). Administration of solifenacin succinate to pregnant rats and rabbits at a dose of 50 mg/kg/day (< 1 times and 1.8 times the systemic exposure at the MRHD, respectively), resulted in no findings of embryo-fetal toxicity. Oral pre- and post-natal administration of solifenacin succinate at 100 mg/kg/day (3.6 times the systemic exposure at the MRHD) during the period of organogenesis through weaning, resulted in reduced peripartum and postnatal survival, reduced body weight gain by the pups, and delayed physical development (eye opening and vaginal patency). An increase in the percentage of male offspring was also observed in litters from offspring (F2 generation) exposed to maternal doses of 250 mg/kg/day. There were no effects on natural delivery in mice treated with 1.2 times (30 mg/kg/day) the expected systemic exposure at the MRHD.

8.2 Lactation

Risk Summary

There is no information on the presence of solifenacin in human milk, the effects on the breastfed child, or the effects on milk production. Solifenacin is present in mouse milk [see Data ]. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for solifenacin succinate tablets and any potential adverse effects on the breastfed child from solifenacin succinate tablets or from the underlying maternal condition.

Data

Animal Data

Oral administration of 14 C-solifenacin succinate to lactating mice resulted in the recovery of radioactivity in maternal milk. Lactating female mice orally administered solifenacin succinate at a maternally toxic dose of 100 mg/kg/day (3.6 times the systemic exposure at the MRHD) had increased postpartum pup mortality, pups with reduced body weights, or delays in the onset of reflex and physical development. Pups from lactating dams orally administered solifenacin succinate at a dose of 30 mg/kg/day (1.2 times the systemic exposure at the MRHD) had no discernible adverse findings. The concentrations of solifenacin in animal milk does not necessarily predict the concentration of drug in human milk.

8.4 Pediatric Use

The safety and effectiveness of solifenacin succinate tablets have not been established in pediatric patients.

8.5 Geriatric Use

In placebo-controlled clinical studies, similar safety and effectiveness were observed between geriatric patients (623 patients ≥ 65 years and 189 patients ≥ 75 years) and younger adult patients (1188 patients < 65 years) treated with solifenacin succinate tablets [see Clinical Pharmacology (12.3)].

8.6 Renal Impairment

Solifenacin plasma concentrations are greater in patients with severe renal impairment compared to subjects with normal renal function [see Clinical Pharmacology (12.3)]. Because increased solifenacin plasma concentrations increase the risk of antimuscarinic adverse reactions, the maximum recommended dose of solifenacin succinate tablets in patients with severe renal impairment (CLcr < 30 mL/min/1.73 m2) is 5 mg once daily [see Dosage and Administration (2.2)]. The recommended dose in patients with mild or moderate renal impairment is the same as in patients with normal renal function.

8.7 Hepatic Impairment

Solifenacin plasma concentrations are greater in patients with moderate hepatic impairment compared to subjects with normal hepatic function [see Clinical Pharmacology ( 12.3)]. Because increased solifenacin plasma concentrations increase the risk of antimuscarinic adverse reactions, the maximum recommended dose of solifenacin succinate tablets in patients with moderate hepatic impairment (Child-Pugh B) is 5 mg once daily [see Dosage and Administration ( 2.3)] and solifenacin succinate tablets is not recommended for use in patients with severe hepatic impairment (Child-Pugh C).

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.