Solifenacin 10 Mg/5 mg Tablets

SOLIFENACIN UNICHEM 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 SOLIFENACIN UNICHEM 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 efficacy of SOLIFENACIN UNICHEM in children have not yet been established. Therefore, SOLIFENACIN UNICHEM is not recommended for children.
Method of administration
SOLIFENACIN UNICHEM should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

• Hypersensitivity to solifenacin succinate or to any of the excipients of SOLIFENACIN UNICHEM 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 lactation (see section 4.6).

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with SOLIFENACIN UNICHEM. If urinary tract infection is present, an appropriate antibacterial therapy should be started. SOLIFENACIN UNICHEM should be used with caution in patients with:

• clinically significant decompensated bladder outflow obstruction at risk of urinary retention,
• gastrointestinal obstructive disorders,
• risk of decreased gastrointestinal motility,
• severe renal impairment (creatinine clearance u2264 30 mL/min; see section 4.2 and 5.2), and doses should not exceed 5 mg for these patients,
• moderate hepatic impairment (Child-Pugh score of 7 to 9; see section 4.2 and 5.2), and doses should not exceed 5 mg for these patients,
• concomitant use of a potent CYP3A4 inhibitor, e.g. ketoconazole (see sections 4.2 and 4.5),
• hiatus hernia/gastro-oesophageal reflux and/or who are concurrently taking medicines (such as bisphosphonates) that can cause or exacerbate oesophagitis,
• autonomic neuropathy.

QT prolongation and torsades de pointes have been observed in patients with risk factors, such as pre-existing 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 SOLIFENACIN UNICHEM. If angioedema occurs, SOLIFENACIN UNICHEM should be discontinued and appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with SOLIFENACIN UNICHEM. In patients who develop anaphylactic reactions, SOLIFENACIN UNICHEM should be discontinued and appropriate therapy and/or measures should be taken. The maximum effect of SOLIFENACIN UNICHEM can be determined after 4 weeks at the earliest. Lactose SOLIFENACIN UNICHEM contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take SOLIFENACIN UNICHEM.

Pharmacological interactions
Concomitant medication with other medicines with anticholinergic properties may result in more pronounced therapeutic effects and undesirable effects. An interval of approximately one week should be allowed after stopping treatment with SOLIFENACIN UNICHEM, before commencing other anticholinergic therapy. The therapeutic effect of SOLIFENACIN UNICHEM may be reduced by concomitant administration of cholinergic receptor agonists. SOLIFENACIN UNICHEM 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 CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, SOLIFENACIN UNICHEM is unlikely to alter the clearance of medicines metabolised by these CYP enzymes.
Effect of other medicines on the pharmacokinetics of SOLIFENACIN UNICHEM
Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates, inhibitors and inducers. Simultaneous administration of ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, 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 SOLIFENACIN UNICHEM should be restricted to 5 mg, when used simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. ritonavir, nelfinavir, itraconazole) (see section 4.2). Simultaneous treatment of SOLIFENACIN UNICHEM and a potent 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 UNICHEM and its metabolites have not been studied as well as the effect of higher affinity CYP3A4 substrates on solifenacin exposure. Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. verapamil, diltiazem) and CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine).
Effect of SOLIFENACIN UNICHEM on the pharmacokinetics of other medicines
Oral contraceptives
Intake of SOLIFENACIN UNICHEM showed no pharmacokinetic interaction between solifenacin and combined oral contraceptives (ethinyl oestradiol/levonorgestrel), both CYP3A4 substrates.
Warfarin
Intake of SOLIFENACIN UNICHEM did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
Digoxin
Intake of SOLIFENACIN UNICHEM showed no effect on the pharmacokinetics of digoxin.

Pregnancy
The use of SOLIFENACIN UNICHEM is contraindicated during pregnancy (see section 4.3). No clinical data are available from women who became pregnant while taking SOLIFENACIN UNICHEM. Foetal toxicity has been shown in rodents.
Breastfeeding
Solifenacin is excreted into breastmilk. Women taking SOLIFENACIN UNICHEM should not breastfeed their infants.
Fertility
No data are available on the effect of SOLIFENACIN UNICHEM on fertility.

SOLIFENACIN UNICHEM may cause blurred vision, somnolence, fatigue and possibly hallucinations and dizziness (see section 4.8), which may affect the ability to drive and use machines.

Summary of the safety profile
Due to the pharmacological effect of solifenacin, SOLIFENACIN UNICHEM may cause anticholinergic undesirable effects of mild or moderate severity in general. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reaction with SOLIFENACIN UNICHEM is dry mouth. The severity of dry mouth is generally mild.
Tabulated summary of adverse reactions
Infections and infestations
Less frequent: urinary tract infection, cystitis
Nervous system disorders
Less frequent: somnolence, dysgeusia
Eye disorders
Frequent: blurred vision
Less frequent: dry eyes
Respiratory, thoracic and mediastinal disorders
Less frequent: nasal dryness
Gastrointestinal disorders
Frequent: dry mouth, constipation, nausea, dyspepsia, abdominal pain
Less frequent: gastro-oesophageal reflux diseases, dry throat, colonic obstruction, faecal impaction
Skin and subcutaneous tissue disorders
Less frequent: dry skin
Renal and urinary disorders
Less frequent: difficulty in micturition, urinary retention
General disorders and administration site conditions
Less frequent: fatigue, peripheral oedema
Post-marketing experience
Immune system disorders
Frequency unknown: anaphylactic reaction
Metabolism and nutrition disorders
Frequency unknown: decreased appetite, hyperkalaemia
Psychiatric disorders
Less frequent: hallucinations, confusional state
Frequency unknown: delirium
Nervous system disorders
Less frequent: dizziness, headache
Eye disorders
Frequency unknown: glaucoma
Cardiac disorders
Frequency unknown: torsades de pointes, electrocardiogram QT prolonged, atrial fibrillation, palpitations, tachycardia
Respiratory, thoracic and mediastinal disorders
Frequency unknown: dysphonia
Gastrointestinal disorders
Less frequent: vomiting
Frequency unknown: ileus, abdominal discomfort
Hepatobiliary disorders
Frequency unknown: liver disorder, liver function test abnormal
Skin and subcutaneous tissue disorders
Less frequent: pruritis, rash, erythema multiforme, urticaria, angioedema
Frequency unknown: exfoliative dermatitis
Musculoskeletal and connective tissue disorders
Frequency unknown: muscular weakness
Renal and urinary disorders
Frequency unknown: renal impairment
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of SOLIFENACIN UNICHEM is important. It allows continued monitoring of the benefit/risk balance of SOLIFENACIN UNICHEM. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Symptoms
Overdosage with SOLIFENACIN UNICHEM can potentially result in severe anticholinergic effects. The highest dose of solifenacin succinate accidentally given to a single patient was 280 mg in a 5-hour period, resulting in mental status changes not requiring hospitalisation.
Treatment
In the event of overdose with SOLIFENACIN UNICHEM, the patient should be treated with activated charcoal. As for other anticholinergics, symptoms can be treated as follows:
u2212 Severe central anticholinergic effects, such as hallucinations or pronounced excitation: treat with physostigmine or carbachol.
u2212 Convulsions or pronounced excitation: treat with benzodiazepines.
u2212 Respiratory insufficiency: treat with artificial respiration.
u2212 Tachycardia: treat with beta-blockers.
u2212 Urinary retention: treat with catheterisation.
u2212 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, congestive heart failure).