Vesinac 10 mg

INDICATIONS

Solifenacin Succinate is indicated for symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

PHARMACOLOGY

Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

DOSAGE & ADMINISTRATION

The recommended dose for adults and the elderly: Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily.Use in children: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.

INTERACTION

Concomitant medication with other medicinal products 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 Succinate before commencing other anticholinergic therapy. The therapeutic effect of Solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as Metoclopramide and Cisapride. 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 is unlikely to alter the clearance of drugs metabolized by these CYP enzymes. Solifenacin is metabolized 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 Solifenacin Succinate 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 Solifenacin and a potent CYP3A4 inhibitor is contra-indicated 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. 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 on the pharmacokinetics of other medicinal products:

Oral Contraceptives: Intake of Solifenacin showed no pharmacokinetic interaction on combined oral contraceptives (Ethinylestradiol/Levonorgestrel).
Warfarin: Intake of Solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.
Digoxin: Intake of Solifenacin showed no effect on the pharmacokinetics of digoxin.
Effects on ability to drive and use machines: Since Solifenacin, like other anticholinergics may cause blurred vision and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.

SIDE EFFECTS

Due to the pharmacological effect of Solifenacin, it may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reactionwith Solifenacin is dry mouth. It occurred in 11% of patients treated with 5 mg once daily, in 22% of patients treated with 10 mg once daily and in 4% of placebo-treated patients. The severity of dry mouth was generally mild and only occasionally led to discontinuation of treatment. In general,medicinal product compliance was very high (approximately 99%) and approximately 90% of the patients treated with Solifenacin completed the full study period of 12 weeks treatment.

Gastrointestinal disorders: very common- dry mouth, common-constipation, nausea, dyspepsia, abdominal pain, uncommon- gastroesophageal reflux diseases, dry throat, rare- colonic obstruction, faecal impaction, very rare- vomiting.
Infections and infestations: uncommonurinary tract infection, cystitis.
nervous system disorders: uncommon- somnolence, dysgeusia, very rare-dizziness, headache.
psychiatric disorders: very rare- hallucinations.
eye disorders: common- blurred vision, uncommon- dry eyes.
General disorders and administration site conditions: uncommon- fatigue, peripheral oedema.
Respiratory, thoracic and mediastinal disorders: uncommon nasal dryness.
skin and subcutaneous tissue disorders: uncommon- dry skin, very rare- pruritus, rash, urticaria.
renal and urinary disorders: uncommon- difficulty in micturition, rare- urinary retention.

PREGNANCY & LACTATION

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. The potential risk for humans is unknown. Caution should be exercised when prescribing to pregnant women. No data on the excretion of Solifenacin 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. The use of Solifenacin should therefore be avoided during breast-feeding.

PRECAUTIONS & WARNINGS

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin Succinate. If urinary tract infection is present, an appropriate antibacterial therapy should be started. Solifenacin Succinate 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 30 ml/min), moderate hepatic impairment (Child-Pugh score of 7 to 9) and doses should not exceed 5 mg for these patients. Caution should be taken in concomitant use of a potent CYP3A4 inhibitor e.g. Ketoconazole, hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as Bisphosphonates) that can cause or exacerbate oesophagitis, autonomic neuropathy. Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. The maximum effect of Solifenacin Succinate can be determined after 4 weeks at the earliest.

USE IN 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 <30 ml/min) should be treated with caution and receive no 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 no more than 5 mg once daily. Potent inhibitors of cytochrome P450 3A4: The maximum dose of Solifenacin Succinate should be limited to 5 mg when treated simultaneously with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. Ritonavir, Nelfinavir, Itraconazole. Solifenacin Succinate tablet should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

THERAPEUTIC CLASS

Anticholinergics (antimuscarinics)/ Anti-spasmodics, BPH/ Urinary retention/ Urinary incontinence

STORAGE CONDITIONS

Store in a cool and dry place, protected from light.