Floloc Chews 5 mg and 10 mg Chewable tablets.

FLOLOC CHEWS 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 (Child - Pugh score of 7 to 9) should be treated with caution and receive not more than 5 mg once daily.

Potent inhibitors of cytochrome P450 3A4

The maximum dose of FLOLOC CHEWS should be limited to 5 mg when treated simultaneously with ketoconazole or therapeutic doses of other CYP3A4-inhibitors e.g. ritonavir, nelfinavir, itraconazole.

Paediatric population

Safety and effectiveness in children have not yet been established. Therefore, FLOLOC CHEWS is not recommended for children.

Method of administration:

FLOLOC CHEWS should be taken orally and chewed. It can be taken with or without food, as is convenient.

FLOLOC CHEWS is contra-indicated in the following situations:

• Hypersensitivity to the solifenacin or to any of the excipients of FLOLOC CHEWS (see 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 (Creatine clearance u02c2 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)

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 FLOLOC CHEWS. If urinary tract infection is present, an appropriate antibacterial therapy should be started.

FLOLOC CHEWS 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 (Child - Pugh score of 7 to 9), and doses should not exceed 5 mg for these patients.
• Concomitant use of a potent CYP3A4 inhibitor, e.g. ketoconazole
• Hiatus hernia/gastro-oesophageal reflux and/or who are currently taking medicinal products (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. 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. If angioedema occurs, FLOLOC CHEWS should be discontinued and appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with solifenacin. In patients who develop anaphylactic reactions, FLOLOC CHEWS should be discontinued and appropriate therapy and/or measures should be taken. The maximum effect of FLOLOC CHEWS can be determined after 4 weeks at the earliest. FLOLOC CHEWS contains lactose. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose should not take FLOLOC CHEWS. FLOLOC CHEWS contains mannitol and may have laxative effect.

Pharmacological interactions:

Concomitant medication 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 FLOLOC CHEWS, before commencing other anticholinergic therapy. The therapeutic effect of FLOLOC CHEWS may be reduced by concomitant administration of cholinergic receptor agonists. FLOLOC CHEWS 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, FLOLOC CHEWS is unlikely to alter the clearance of medicines metabolised by these CYP enzymes.

Effects 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. Ketoconazole and other CYP3A4 inhibitors: 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 FLOLOC CHEWS should be restricted to 5 mg, when used with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors. Simultaneous treatment of FLOLOC CHEWS and strong CYP3A4 inhibitors is contra-indicated in patients with severe renal impairment or moderate hepatic impairment (see section 4.3).

Effects of Solifenacin on the pharmacokinetics of other medicines:

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

Pregnancy: FLOLOC CHEWS is contraindicated during pregnancy (see section 4.3) Foetal toxicity has been shown in rodents.

Breastfeeding: Solifenacin is excreted into breastmilk. Women taking FLOLOC CHEWS should not breastfeed their infants.

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

Summary of safety profile

Due to the pharmacological effect of solifenacin, FLOLOC CHEWS may cause anticholinergic side effects of mild to moderate severity in general. The frequency of anticholinergic side effects is dose related. The most frequently reported adverse reaction was dry mouth. The severity of dry mouth was generally mild.

Summary of adverse reactions

Infections and infestations: Less frequent: Urinary tract infection, cystitis.

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: Somnolence, dysgeusia, dizziness, headache.

Eye disorders: Frequent: Blurred vision. Less frequent: Dry eyes. Frequency unknown: Glaucoma.

Cardiac disorders: Frequency unknown: Torsades de Pointes, electrocardiogram QT prolonged, atrial fibrillation, palpitations, tachycardia.

Respiratory, thoracic and mediastinal disorders: Less frequent: Nasal dryness. Frequency unknown: Dysphonia.

Gastro-intestinal disorders: Frequent: Dry mouth, constipation, nausea, dyspepsia, abdominal pain. Less frequent: Gastro-oesophageal reflux diseases, dry throat, colonic obstruction, faecal impaction, vomiting. Frequency unknown: Ileus, abdominal discomfort.

Hepatobiliary disorders: Frequency unknown: Liver disorder, liver function test abnormal.

Skin and subcutaneous tissue disorders: Less frequent: Dry skin, pruritis, rash, erythema multiforme, urticaria, angioedema. Frequency unknown: Exfoliative dermatitis.

Musculoskeletal and connective tissue disorders: Frequency unknown: Muscular weakness.

Renal and urinary disorders: Less frequent: Difficulty in micturition, urinary retention. Frequency unknown: Renal impairment.

General disorders and administration site conditions: Less frequent: Fatigue, peripheral oedema.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals 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 and signs:

Overdose with FLOLOC CHEWS can potentially result in severe anticholinergic effects. After receiving a single dose of 100 mg Solifenacin succinate, the most frequent adverse events were headache, dry mouth, dizziness, drowsiness and blurred vision.

Treatment:

In the event of overdosage with FLOLOC CHEWS 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 medicinal products known to prolong QT-interval) and relevant pre-existing cardiac disease (i.e. myocardial ischemia, dysrhythmia, congestive heart failure).