Utrobin Tablet 10mg

Product Information

UTROBIN

Utrobin® (Solifenacin Succinate INN)

Presentation

Utrobin 5 mg tablet: Yellow, diamond shaped tablet; each film-coated tablet contains Solifenacin Succinate INN 5 mg.

Utrobin 10 mg tablet: Pink, diamond shaped tablet; each film-coated tablet contains Solifenacin Succinate INN 10 mg.

Indications

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive

bladder syndrome.

Dosage and administration

Adults, including the elderly: The recommended dose is Solifenacin Succinate 5 mg (one Utrobin 5 mg tablet) once daily. If needed,

the dose may be increased to Solifenacin Succinate 10 mg (one Utrobin 10 mg tablet) once daily.

Children and adolescents: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate

should not be used in children.

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 (one Utrobin 5 mg tablet) 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 (one Utrobin 5 mg tablet) once daily. Potent inhibitors of cytochrome P450

3A4: The maximum dose of Solifenacin Succinate should be limited to 5 mg (one Utrobin 5 mg tablet) when treated simultaneously

with Ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. Ritonavir, Nelfinavir, Itraconazole. Solifenacin

Succinate tablet (Utrobin tablet) should be taken orally and should be swallowed whole with liquids. It can be taken with or

without food.

Contra-indications, warnings etc.

Contra-indications: Solifenacin is contra-indicated in patients with hypersensitivity to Solifenacin, urinary retention, severe

gastrointestinal condition (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma, patients undergoing

haemodialysis, patients with severe hepatic impairment, patients with severe renal impairment or moderate hepatic impairment

and who are on treatment with a potent CYP3A4 inhibitor, e.g. Ketoconazole.

Warnings and precautions: 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 pregnancy and 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. Side effect: 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.

Drug interactions: 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.

Overdose: Over dosage with Solifenacin Succinate 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 hospitalization. In the event of overdose with Solifenacin Succinate, the patient should be treated with

activated charcoal. Gastric lavage is useful if performed within 1 hour, but vomiting should not be induced. 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 a dark room.

As with other antimuscarinics, 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 medicinal products known to prolong QT-interval)

and relevant pre-existing cardiac diseases (i.e. myocardial ischaemia, arrhythmia, congestive heart failure).

Pharmaceutical precautions

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

Packaging quantity

Utrobin 5 mg tablet: Cartons containing 30 tablets in blister.

Utrobin 10 mg tablet: Cartons containing 20 tablets in blister.