Solirest 5 & 10 5 mg. 10 mg Tablet

Solirest 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.

Strong inhibitors of cytochrome P450 3A4

The maximum dose of Solirest should be limited to 5 mg when treated simultaneously with ketoconazole or therapeutic doses of other strong CYP3A4-inhibitors.

Paediatric population

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

Method of administration

Solirest should be taken orally and should be swallowed whole with liquids. It can be taken with or without food, as is convenient.

• Hypersensitivity to solifenacin succinate or to any of the excipients of Solirest.
• Patients with urinary retention, severe gastro-intestinal condition (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma and in patients at risk for these conditions.
• Patients undergoing haemodialysis (see section 5.2)
• Patients with severe hepatic impairment (see section 5.2)
• Patients with severe renal impairment (CLcr u02c2 30 mL/ min) or moderate hepatic impairment and who are on treatment with a potent CYP3A4 inhibitor, e.g. ketoconazole (see section 4.5).

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solirest. If urinary tract infection is present, an appropriate antibacterial therapy should be started.

Solirest should be used with caution in patients with:

• clinically significant 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 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 Torsade 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 Solirest. If angioedema occurs, Solirest should be discontinued and appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with Solirest. In patients who develop anaphylactic reactions, Solirest should be discontinued and appropriate therapy and/or measures should be taken. The maximum effect of Solirest can be determined after 4 weeks at the earliest. Contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Solirest.

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 Solirest, before commencing other anticholinergic therapy. The therapeutic effect of Solirest may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin succinate as in Solirest 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 succinate as in Solirest is unlikely to alter the clearance of medicines metabolised by these CYP enzymes.

Effect of other medicines on the pharmacokinetics of solifenacin

Solifenacin is metabolised by CYP3A4. 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 Solirest 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 Solirest and a potent CYP3A4 inhibitor is contraindicated in patients with severe renal impairment or moderate hepatic impairment. 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 Solirest showed no pharmacokinetic interaction of solifenacin on combined oral contraceptives (ethinylestradiol/levonorgestrel).
Warfarin: Intake of Solirest did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
Digoxin: Intake of Solirest showed no effect on the pharmacokinetics of digoxin.

Pregnancy

No clinical data are available from women who became pregnant while taking solifenacin. Animal studies do not indicate direct harmful effects on fertility, embryonal / foetal development or parturition (see section 5.3). The potential risk for humans is unknown. Safety in pregnancy and lactation has not been established.

Breastfeeding

No data on the excretion of Solirest in human milk are available. In mice, solifenacin and/or its metabolites was excreted in milk, and caused a dose dependent failure to thrive in neonatal mice (see Section 5.3). The use of Solirest should therefore be avoided during breastfeeding.

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

Summary of the safety profile

Due to the pharmacological effect of solifenacin, Solirest may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most frequently reported adverse reaction with Solirest was dry mouth. The severity of dry mouth was generally mild and did only occasionally lead to discontinuation of treatment.

Tabulated list of adverse reactions

* Observed post-marketing

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 providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who- umc.org) found on SAHPRA website.

Symptoms

The highest dose of solifenacin succinate given to human volunteers was 100 mg as a single dose. At this dose, the most frequent adverse events were headache, dry mouth, dizziness, drowsiness and blurred vision.

Treatment

No cases of acute overdosage have been reported. In the event of overdose with Solirest the patient should be treated symptomatically and with activated charcoal. Vomiting should not be induced. 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.

In case of overdosing, 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, arrhythmia, congestive heart failure).