Chemical formula: C₂₃H₂₆N₂O₂ Molecular mass: 362.473 g/mol PubChem compound: 154059
Solifenacin interacts in the following cases:
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, before commencing other anticholinergic therapy.
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, carbamazepin).
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 solifenacin should be restricted to 5 mg (5 ml) for adults or the starting dose for children and adolescents, when used simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. ritonavir, nelfinavir, itraconazole).
Patients with severe renal impairment (creatinine clearance ≤30 ml/min) should be treated with caution and receive no more than 5 mg (5 ml) once daily (adults) and no more than the starting dose (children and adolescents).
Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastro-intestinal tract, such as metoclopramide and cisapride.
Solifenacin should be used with caution in patients with gastrointestinal obstructive disorders.
Solifenacin should be used with caution in patients with clinically significant bladder outflow obstruction in the absence of clean intermittent catheterization because of the risk of urinary retention.
Solifenacin should be used with caution in patients with autonomic neuropathy.
Angioedema with airway obstruction has been reported in some patients on solifenacin. If angioedema occurs, solifenacin should be discontinued and appropriate therapy and/or measures should be taken.
Solifenacin should be used with caution in patients with hiatus hernia/gastro-oesophageal reflux and/or who are concurrently taking medicinal products (such as bisphosphonates) that can cause or exacerbate oesophagitis.
Solifenacin should be used with caution in patients with risk of decreased gastrointestinal motility.
QT prolongation and Torsade de Pointes have been observed in patients taking solifenacin with risk factors, such as pre-existing long QT syndrome and hypokalaemia.
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.
There are no clinical data available on effects of solifenacin on fertility. No effects on fertility were observed in animals.
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.
Due to the pharmacological effect of solifenacin, solifenacin 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 reaction with solifenacin was 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 did only occasionally lead 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.
Very common ≥1/10, Common ≥1/100, <1/10, Uncommon ≥1/1000, <1/100, Rare ≥1/10000, <1/1000, Very rare <1/10,000, Not known (cannot be estimated from the available data).
Uncommon: Urinary tract infection, Cystitis
Not known: Anaphylactic reaction*
Not known: Decreased appetite*, Hyperkalaemia*
Very rare: Hallucinations*, Confusional state*
Not known: Delirium*
Uncommon: Somnolence, Dysgeusia
Rare: Dizziness*, Headache*
Common: Blurred vision
Uncommon: Dry eyes
Not known: Glaucoma*
Not known: Torsade de Pointes*, Electrocardiogram QT prolonged*, Atrial fibrillation*, Palpitations*, Tachycardia*
Uncommon: Nasal dryness
Not known: Dysphonia*
Very common: Dry mouth
Common: Constipation, Nausea, Dyspepsia, Abdominal pain
Uncommon: Gastro-oesophageal reflux diseases, Dry throat
Rare: Colonic obstruction, Faecal impaction, Vomiting*
Not known: Ileus*, Abdominal discomfort*
Not known: Liver disorder*, Liver function test abnormal*
Uncommon: Dry skin
Rare: Pruritus*, Rash*
Very rare: Erythema multiforme*, Urticaria*, Angioedema*
Not known: Exfoliative dermatitis*
Not known: Muscular weakness*
Uncommon: Difficulty in micturition
Rare: Urinary retention
Not known: Renal impairment*
Uncommon: Fatigue, Peripheral oedema
* observed post-marketing
Solifenacin oral suspension has been evaluated for safety in 95 paediatric patients aged 2 years to less than 18 years with neurogenic detrusor overactivity in two open-label trials. Common adverse reactions observed in the paediatric population with NDO include: constipation, dry mouth, abdominal pain, somnolence, urinary tract infection, bacterial test positive, and QT prolonged. The incidence of constipation in patients treated with solifenacin oral suspension was higher in the maximum dose group compared to the starting dose group.
In the paediatric patients with NDO, no severe adverse reactions were reported. The most frequent adverse reaction leading to study discontinuation was QT prolongation.
Overall, the safety profile in children and adolescents is similar to that observed in adults.
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