ENABLEX

What it is

Enablex is a modified-release tablet containing darifenacin hydrobromide, available in strengths of 7.5 mg or 15 mg. Darifenacin is a selective muscarinic M3 receptor antagonist that exhibits 9- to 59-fold selectivity for the human M3 receptor over human muscarinergic M1, M2, M4 and M5 receptors. The M3 receptor is the major subtype that controls urinary bladder muscle contraction.

Approved indications

— Treatment of overactive bladder, with the symptoms of urgency, urge urinary incontinence or frequency of micturition.

Dosing overview

The recommended starting dose of Enablex modified-release tablets is 7.5 mg once daily. For those patients requiring greater symptom relief, the dose may be increased to 15 mg daily, as early as two weeks after starting therapy, based on individual response. Enablex modified-release tablets should be taken once daily with liquid, may be taken with or without food, and should be swallowed whole and not chewed, divided or crushed. For patients with moderate hepatic impairment (Child Pugh B) or when co-administered with potent CYP3A4 inhibitors (such as ketoconazole, itraconazole, miconazole, nefazodone and ritonavir), the daily dose of Enablex should not exceed 7.5 mg. There are no special dosage requirements for patients with renal impairment.

Key safety warnings

Enablex should be administered with caution to patients with autonomic neuropathy, hiatus hernia, clinically significant bladder outflow obstruction, risk for urinary retention, severe constipation (defined as two or less bowel movements per week) or gastrointestinal obstructive disorders, such as pyloric stenosis. As with other antimuscarinics, patients should be instructed to discontinue Enablex and seek immediate medical attention if they experience edema of the tongue or laropharynx, or difficulty breathing. Enablex should be used with caution in patients with risk of decreased gastrointestinal motility, gastro-oesophagal reflux and/or who are concurrently taking medicinal products (such as oral bisphosphonates) that can cause or exacerbate oesophagitis. Caution should be used when prescribing antimuscarinics to patients with pre-existing cardiac diseases. The most frequently reported adverse events were dry mouth and constipation. Adverse events were reported by 54.0% and 65.6% of patients receiving 7.5 and 15 mg once daily Enablex modified-release tablets, respectively.

Contraindications

Enablex is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, urinary retention, gastric retention or uncontrolled narrow-angle glaucoma. Enablex is not recommended for use in patients with severe hepatic impairment (Child Pugh C).

Regulatory history

Enablex darifenacin 7.5 mg and 15 mg modified-release tablets were first listed on the Australian Register of Therapeutic Goods on 16 March 2005. The first approval date in Australia was 9 August 2010.