Detrusitol SR

/ Dexcel

The recommended dose is 4 mg daily. This product should be taken once daily with liquids and swallowed whole. The dose may be lowered to 2 mg daily based on individual response and tolerability, however, limited efficacy data is available for 2 mg.
For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose is 2 mg daily.

Overactive bladder with symptoms of urinary frequency, urgency or urge incontinence.

DETRUSITOL® SR is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. DETRUSITOL® SR is also contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients, or to fesoterodine fumarate extended-release tablets which, like DETRUSITOL® SR, are metabolized to 5-hydroxymethyl tolterodine.

Angioedema: Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of DETRUSITOL® SR. In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, DETRUSITOL® SR should be discontinued and appropriate therapy promptly provided.
Urinary Retention: Administer DETRUSITOL® SR Capsules with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
Gastrointestinal Disorders: Administer DETRUSITOL® SR with caution in patients with gastrointestinal obstructive disorders because of the risk of gastric retention.
DETRUSITOL® SR, like other antimuscarinic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions associated with decreased gastrointestinal motility (e.g., intestinal atony).
Controlled Narrow-Angle Glaucoma: Administer DETRUSITOL® SR with caution in patients being treated for narrow-angle glaucoma.
Central Nervous System Effects: DETRUSITOL® SR is associated with anticholinergic central nervous system (CNS) effects including dizziness and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until the drug’s effects have been determined. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.
Hepatic Impairment: The clearance of orally administered tolterodine immediate release was substantially lower in cirrhotic patients than in the healthy volunteers. For patients with mild to moderate hepatic impairment (Child-Pugh Class A or B), the recommended dose for DETRUSITOL® SR is 2 mg once daily. DETRUSITOL® SR is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C).
Renal Impairment: Renal impairment can significantly alter the disposition of tolterodine and its metabolites. The dose of DETRUSITOL® SR should be reduced to 2 mg once daily in patients with severe renal impairment (CCr: 10-30 mL/min). Patients with CCr<10 mL/min have not been studied and use of DETRUSITOL® SR in this population is not recommended.
Myasthenia Gravis: Administer DETRUSITOL® SR with caution in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.
Use in Patients with Congenital or Acquired QT Prolongation: In a study of the effect of tolterodine immediate release tablets on the QT interval, the effect on the QT interval appeared greater for 8 mg/day (two times the therapeutic dose) compared to 4 mg/day and was more pronounced in CYP2D6 poor metabolizers (PM) than extensive metabolizers (EMs). The effect of tolterodine 8 mg/day was not as large as that observed after four days of therapeutic dosing with the active control moxifloxacin. However, the confidence intervals overlapped.
These observations should be considered in clinical decisions to prescribe DETRUSITOL ®SR to patients with a known history of QT prolongation or to patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.There has been no association of Torsade de Pointes in the international post-marketing experience with DETRUSITOL® or DETRUSITOL® SR.
Important information regarding some of the ingredients of the medicine: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

The most common adverse events reported by patients receiving DETRUSITOL® SR were dry mouth, headache, constipation, and abdominal pain.
See prescribing information for full details.

Potent CYP2D6 Inhibitors: Fluoxetine, a potent inhibitor of CYP2D6 activity, significantly inhibited the metabolism of tolterodine immediate release in CYP2D6 extensive metabolizers, resulting in a 4.8-fold increase in tolterodine AUC. There was a 52% decrease in Cmax and a 20% decrease in AUC of 5-hydroxymethyl tolterodine (5-HMT), the pharmacologically active metabolite of tolterodine. The sums of unbound serum concentrations of tolterodine and 5-HMT are only 25% higher during the interaction. No dose adjustment is required when tolterodine and fluoxetine are co-administered.
Potent CYP3A4 Inhibitors: Ketoconazole (200 mg daily), a potent CYP3A4 inhibitor, increased the meanCmax and AUC of tolterodine by 2- and 2.5-fold, respectively, in CYP2D6 poor metabolizers.
For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as itraconazole, clarithromycin, or ritonavir, the recommended dose of DETRUSITOL® SR is 2 mg once daily.
Other Interactions: No clinically relevant interactions have been observed when tolterodine was co-administered with warfarin, with a combined oral contraceptive drug containing ethinyl estradiol and levonorgestrel, or with diuretics.
Other Drugs Metabolized by Cytochrome P450 Isoenzymes: In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9, 2C19, or 3A4 as evidenced by lack of influence on the marker drugs caffeine, debrisoquine, S-warfarin, and omeprazole.
Drug-Laboratory-Test Interactions: Interactions between tolterodine and laboratory tests have not been studied.
Other Anticholinergics: The concomitant use DETRUSITOL® SR with other anticholinergic (antimuscarinic) agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision, somnolence, and other anticholinergic pharmacological effects.

Pregnancy: There are no available data with DETRUSITOL® SR use in pregnant women to inform drug-associated risks.
Lactation: There is no information on the presence of tolterodine or its 5-HMT metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. Based on limited data, tolterodine is excreted into the milk in mice in low amounts. The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for DETRUSITOL® SR and any potential adverse effects on the breastfed infant from DETRUSITOL® SR or from the underlying maternal condition.
See prescribing information for full details.

Overdosage with DETRUSITOL® Capsules can potentially result in severe central anticholinergic effects and should be treated accordingly.
ECG monitoring is recommended in the event of overdosage. In dogs, changes in the QT interval (slight prolongation of 10% to 20%) were observed at a suprapharmacologic dose of 4.5 mg/kg, which is about 68 times higher than the recommended human dose. In clinical trials of normal volunteers and patients, QT interval prolongation was observed with tolterodine immediate release at doses up to 8 mg (4 mg bid) and higher doses were not evaluated.
A 27-month-old child who ingested 5 to 7 tolterodine immediate release 2 mg tablets was treated with a suspension of activated charcoal and was hospitalized overnight with symptoms of dry mouth. The child fully recovered.

Storage: Store below 25°C.