Toviaz 4, 8 mg

/ Pfizer

Adults (including elderly): The recommended starting dose is 4 mg once daily. Based upon individual response, the dose may be increased to 8 mg once daily. The maximum daily dose is 8 mg. Full treatment effect was observed between 2 and 8 weeks. Hence, it is recommended to re-evaluate the efficacy for the individual patient after 8 weeks of treatment. In subjects with normal renal and hepatic function receiving concomitant administration of potent CYP3A4 inhibitors, the maximum daily dose of Fesoterodine fumarate should be 4 mg once daily.
Renal and hepatic impairment: The daily dosing recommendations for subjects with renal or hepatic impairment in the absence and presence of moderate and potent CYP3A4 inhibitors:
Renal impairment: 
Mild: None: 4→8 mg, Moderate: 4 mg,  Potent: Should be avoided 
Moderate: None: 4→8 mg, Moderate: 4 mg,  Potent: Contraindicated
Severe: None: 4 mg, Moderate: Should be avoided, Potent: Contraindicated
Hepatic impairment:
Mild: None: 4→8 mg, Moderate: 4 mg,  Potent: Should be avoided 
Moderate: None: 4 mg, Moderate: Should be avoided, Potent: Contraindicated
TOVIAZ is contraindicated in subjects with severe hepatic impairment.
Paediatric population: The safety and efficacy of TOVIAZ in children below 18 years of age have not yet been established. No data are available.
Method of administration: Tablets are to be taken once daily with liquid and swallowed whole. TOVIAZ can be administered with or without food. 

Treatment of the symptoms (increased urinary frequency and/or urgency and/or urgency incontinence) that may occur in patients with overactive bladder syndrome.

Hypersensitivity to the active substance or to peanut or soya or to any of the excipients. Urinary retention. Gastric retention. Uncontrolled narrow angle glaucoma. Myasthenia gravis. Severe hepatic impairment (Child Pugh C). Concomitant use of potent CYP3A4 inhibitors in subjects with moderate to severe hepatic or renal impairment. Severe ulcerative colitis. Toxic megacolon.

Fesoterodine fumarate should be used with caution in patients with: Clinically significant bladder outflow obstruction at risk of urinary retention (e.g. clinically significant prostate enlargement due to benign prostatic hyperplasia. Gastrointestinal obstructive disorders (e.g. pyloric stenosis). Gastro-oesophageal reflux and/or who are concurrently taking medicinal products (such as oral bisphosphonates) that can cause or exacerbate oesophagitis. Decreased gastrointestinal motility. Autonomic neuropathy. Controlled narrow-angle glaucoma.
Caution should be exercised when prescribing or uptitrating fesoterodine to patients in whom an increased exposure to the active metabolite is expected: Hepatic impairment. Renal impairment. Concomitant administration of potent or moderate CYP3A4 inhibitors. Concomitant administration of a potent CYP2D6 inhibitor.
Dose increases: In patients with a combination of these factors, additional exposure increases are expected. Dose dependent antimuscarinic adverse reactions are likely to occur. In populations where the dose may be increased to 8 mg once daily, the dose increase should be preceded by an evaluation of the individual response and tolerability.
Angioedema: Angioedema has been reported with fesoterodine and has occurred after the first dose in some cases. Some cases may be associated with upper airway swelling and may be life-threatening. If angioedema occurs, fesoterodine should be discontinued and appropriate therapy should be promptly provided.
Potent CYP3A4 inducers: The concomitant use of fesoterodine with a potent CYP3A4 inducer (i.e. carbamazepine, rifampicin, phenobarbital, phenytoin, St John’s Wort) is not recommended.
QT prolongation: Fesoterodine fumarate should be used with caution in patients with risk for QT-prolongation (e.g. hypokalaemia, bradycardia and concomitant administration of medicines known to prolong QT interval) and relevant pre-existing cardiac diseases (e.g. myocardial ischaemia, arrhythmia, congestive heart failure). This especially holds true when taking potent CYP3A4 inhibitors.
Lactose: Fesoterodine fumarate prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
See prescribing information for full details.

Insomnia, Dizziness, Headache, Dry eye, Dry throat, Abdominal pain, Diarrhoea, Dyspepsia, Constipation, Nausea, Dysuria.
See prescribing information for full details.

Pharmacological interactions: Caution should be exercised in coadministration of fesoterodine with other antimuscarinics and medicinal products with anticholinergic properties (e.g. amantadine, tri-cyclic antidepressants, certain neuroleptics ) as this may lead to more pronounced therapeutic- and side-effects (e.g. constipation, dry mouth, drowsiness, urinary retention). Fesoterodine may reduce the effect of medicinal products that stimulate the motility of the gastro-intestinal tract, such as metoclopramide.
Pharmacokinetic interactions: In vitro data demonstrate that the active metabolite of fesoterodine does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4, or induce CYP1A2, 2B6, 2C9, 2C19, or 3A4 at clinically relevant plasma concentrations. Thus fesoterodine is unlikely to alter the clearance of medicinal products that are metabolised by these enzymes.
CYP3A4 inhibitors
Potent CYP3A4 inhibitors: Following inhibition of CYP3A4 by co-administration of ketoconazole 200 mg twice daily, Cmax and AUC of the active metabolite of fesoterodine increased 2.0 and 2.3-fold in CYP2D6 extensive metabolisers and 2.1 and 2.5-fold in CYP2D6 poor metabolisers, respectively. Therefore, the maximum dose of fesoterodine should be restricted to 4 mg when used concomitantly with potent CYP3A4 inhibitors (e.g. atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir (and all ritonavir boosted PI-regimens), saquinavir and telithromycin .
Moderate CYP3A4 inhibitors: Following blockade of CYP3A4 by coadministration of the moderate CYP3A4 inhibitor fluconazole 200 mg twice a day for 2 days, Cmax and AUC of the active metabolite of fesoterodine increased approximately 19% and 27%, respectively. No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole, diltiazem, verapamil and grapefruit juice).
See prescribing information for full details.

Pregnancy: There are no adequate data from the use of fesoterodine in pregnant women.
Lactation: It is unknown whether fesoterodine metabolites are excreted into human milk; therefore, breast-feeding is not recommended during treatment with this drug.
See prescribing information for full details.

Overdose with antimuscarinica, including fesoterodine can result in severe anticholinergic effects. Treatment should be symptomatic and supportive. In the event of overdose, ECG monitoring is recommended; standard supportive measures for managing QT prolongation should be adopted. Fesoterodine has been safely administered in clinical studies at doses up to 28 mg/day.
In the event of fesoterodine overdose, treat with gastric lavage and give activated charcoal. Treat symptoms as follows:
– Severe central anticholinergic effects (e.g. hallucinations, severe excitation): treat with physostigmine
– Convulsions or pronounced excitation: treat with benzodiazepines
– Respiratory insufficiency: treat with artificial respiration
– Tachycardia: treat with beta-blockers
– Urinary retention: treat with catheterization
– Mydriasis: treat with pilocarpine eye drops and/or place patient in dark room.

Storage: Do not store above 25C. Store in the original package in order to protect from moisture.