Fensiglen 5 Mg/10 Mg Tablets

FENSIGLEN is indicated for the symptomatic treatment of overactive bladder syndrome: symptoms of urinary urgency, frequent micturition and/ or urge incontinence.

Posology: Adults, including the elderly The recommended dose is 5 mg once daily. If needed, the dose may be increased to 10 mg once daily.

Special populations Patients with renal impairment No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance > 30 mL/min). Patients with severe renal impairment (creatinine clearance u2264 30 mL/min) should be treated with caution and receive not more than 5 mg once daily. Patients with hepatic impairment No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment should be treated with caution and receive not more than 5 mg once daily. Potent inhibitors of cytochrome P450 3A4 The maximum dose of FENSIGLEN should be limited to 5 mg when treated simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4-inhibitors e.g., ritonavir, nelfinavir, itraconazole. Paediatric population Safety and effectiveness of FENSIGLEN in children have not yet been established. Therefore, FENSIGLEN is not recommended for children.

Method of administration FENSIGLEN should be taken orally and should be swallowed whole with liquids. It can be taken with or without food, as is convenient.

FENSIGLEN is contra-indicated:

• In individuals with known hypersensitivity to solifenacin succinate or any of the excipients listed in section 6.1.
• Urinary retention
• Uncontrolled narrow angle glaucoma
• Myasthenia gravis
• Toxic megacolon
• Patients undergoing haemodialysis
• Patients with severe hepatic impairment
• Patients with severe renal impairment (Cl cr < 30 mL/min) and on treatment with a strong CYP3A4 inhibitor, e.g., ketoconazole (see section 4.5)
• Patients with moderate hepatic impairment and on treatment with a strong CYP3A4 inhibitor, e.g., ketoconazole (see section 4.5)
• Patients with a prolonged QT interval, either congenital or acquired
• Pregnancy and breastfeeding (see section 4.6)

Organic reasons for urge and frequent micturition should be excluded before treatment. Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with FENSIGLEN. If urinary tract infection is present, an appropriate antibacterial therapy should be started. FENSIGLEN should be used with caution in patients with:

• Significant decompensated bladder outlet obstruction at risk of urinary retention
• Gastrointestinal obstructive disorders
• Risk of decreased gastrointestinal motility
• Severe renal impairment (creatinine clearance u2264 30 mL/min), and doses should not exceed 5 mg for these patients
• Moderate hepatic impairment, and doses should not exceed 5 mg for these patients
• Concomitant use of a potent CYP3A4 inhibitor, e.g., ketoconazole
• Hiatus hernia/gastro-oesophagal reflux and/or who are concurrently taking medicines (such as bisphosphonates) that can cause or exacerbate oesophagitis
• Autonomic neuropathy

QT prolongation and Torsade de Pointes have been observed in patients with risk factors, such as preexisting long QT syndrome and hypokalaemia (see section 4.3). Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity. Angioedema with airway obstruction has been reported in some patients on FENSIGLEN. If angioedema occurs, FENSIGLEN should be discontinued and appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with solifenacin as contained in FENSIGLEN. In patients who develop anaphylactic reactions, FENSIGLEN should be discontinued and appropriate therapy and/or measures should be taken. The maximum effect of FENSIGLEN can be determined after 4 weeks at the earliest. FENSIGLEN contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption, should not take this medicine.

Pharmacological interactions Concomitant medicine with other medicines with anticholinergic properties may result in more pronounced therapeutic effects and side effects. An interval of approximately one week should be allowed after stopping treatment with FENSIGLEN, before commencing other anticholinergic therapy. The therapeutic effect of FENSIGLEN may be reduced by concomitant administration of cholinergic receptor agonists. FENSIGLEN can reduce the effect of medicines that stimulate the motility of the gastrointestinal tract, such as metoclopramide and cisapride.

Pharmacokinetic interactions In vitro studies have demonstrated that at therapeutic concentrations, solifenacin does not inhibit CYP1A/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, FENSIGLEN is unlikely to alter the clearance of medicines metabolised by these CYP enzymes. Effect of other medicines on the pharmacokinetics of solifenacin Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates, inhibitors and inducers. Simultaneous administration of ketoconazole (200 mg/day) resulted in a two-fold increase of the AUC of solifenacin, while ketoconazole at a dose of 400 mg/day resulted in a three-fold increase of the AUC of solifenacin. Therefore, the maximum dose of FENSIGLEN should be restricted to 5 mg, when used simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g., ritonavir, nelfinavir, itraconazole). Simultaneous treatment of FENSIGLEN and strong CYP3A4 inhibitor is contraindicated in patients with severe renal impairment or moderate hepatic impairment (see section 4.3). The effects of enzyme induction on the pharmacokinetics of solifenacin and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on solifenacin exposure.

Effect of solifenacin on the pharmacokinetics of other medicines Oral contraceptives Intake of FENSIGLEN showed no pharmacokinetic interaction between solifenacin and combined oral contraceptives (ethinyl oestradiol/levonorgestrel), both CYP3A4 substrates. Warfarin Intake of FENSIGLEN did not alter the pharmacokinetics of R-warfarin (substrate for CYP3A4) or S-warfarin (substrate for CYP2C9) or their effect on the INR. Digoxin Intake of FENSIGLEN showed no effects on the pharmacokinetics of digoxin.

Pregnancy FENSIGLEN is contraindicated during pregnancy (see section 4.3). Foetal toxicity has been shown in rodents. Breastfeeding Solifenacin is excreted into breast milk. Women taking FENSIGLEN should not breastfeed their infants. Fertility No data available.

Since FENSIGLEN may cause blurred vision, somnolence and fatigue (see section 4.8), the ability to drive and use machines may be negatively affected.

Due to the pharmacological effect of solifenacin, FENSIGLEN may cause anticholinergic side effects of mild or moderate severity in general. The frequency of anticholinergic side effects is dose related. The most commonly reported adverse reaction with solifenacin as contained in FENSIGLEN was dry mouth.

Tabulated summary of adverse reactions The adverse reactions are listed by system organ class and absolute frequency.

System Organ Class Adverse Reactions Frequency Category Infections and infestations Urinary tract infection, cystitis Less frequent Immune system disorders Anaphylactic reaction Frequency unknown Metabolism and nutrition disorders Decreased appetite, hyperkalaemia Frequency unknown Psychiatric disorders Hallucinations, confusional state Less frequent Delirium Frequency unknown Nervous system disorders Somnolence, dysgeusia, dizziness, headache Less frequent Eye disorders Blurred vision Frequent Dry eyes Less frequent Glaucoma Frequency unknown Cardiac disorders Torsade de Pointes, electrocardiogram QT prolonged Frequency unknown Nasal dryness Less frequent Respiratory, thoracic and mediastinal disorders Dysphonia Frequency unknown Gastrointestinal disorders Dry mouth, constipation, nausea, dyspepsia, abdominal pain Frequent Gastrooesophageal reflux diseases, dry throat, colonic obstruction, faecal impaction Less frequent Ileus, abdominal discomfort Frequency unknown Hepato-biliary disorders Liver disorder, liver function test abnormal Frequency unknown Skin and subcutaneous tissue disorders Dry skin, pruritus, rash, erythema Multiforme, urticaria, angioedema Less frequent Exfoliative dermatitis Frequency unknown Musculoskeletal and Connective tissue disorders Muscular weakness Frequency unknown Renal and urinary disorders Difficulty in micturition, urinary retention Less frequent Renal impairment Frequency unknown General disorders and administration site conditions Fatigue, peripheral oedema Less frequent

Symptoms Overdosage with solifenacin succinate can potentially result in severe anticholinergic effects. Treatment In the event of overdose with FENSIGLEN the patient should be treated with activated charcoal. As for other anticholinergics, symptoms can be treated as follows:

• Severe central anticholinergic effects such as hallucinations or pronounced excitation: treat with physostigmine or carbachol
• Convulsions or pronounced excitation: treat with benzodiazepines
• Respiratory insufficiency: treat with artificial respiration
• Tachycardia: treat with beta-blockers
• Urinary retention: treat with catheterisation
• Mydriasis: treat with pilocarpine eye drops and/or place patient in dark room

Specific attention should be paid to patients with known risk for QT-prolongation (i.e., hypokalaemia, bradycardia and concurrent administration of medicines known to prolong QT-interval) and relevant pre-existing cardiac diseases (i.e., myocardial ischaemia, dysrhythmia, arrhythmia, congestive heart failure).