Enablex 7.5mg Tablet

ENABLEX is indicated for the treatment of overactive bladder with symptoms of urinary urgency, frequency and /or urge incontinence.

Adults: The recommended starting dose is 7,5 mg 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 and tolerability.

ENABLEX controlled-release tablets should be taken once daily with liquid. They may be taken with or without food, and should be swallowed whole and not chewed, divided or crushed.

Elderly patients: Dose adjustment is not required in elderly patients (see Pharmacokinetic properties).

Use in renal impairment: Dose adjustment is not required in patients with impaired renal function (see Pharmacokinetic properties).

Use in hepatic impairment: The daily dose of ENABLEX should not exceed 7,5 mg in patients with moderate hepatic impairment (Child Pugh B). ENABLEX is not recommended for use in patients with severe hepatic impairment (Child Pugh C).

Hypersensitivity to the active substance or to any of the excipients. Co-administration with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, miconazole, troleandomycin, nefazadone, ritonavir, nelfinavir and clarithromycin. ENABLEX is contraindicated in patients with urinary retention, gastric retention or uncontrolled narrow-angle glaucoma. Severe hepatic impairment.

Children under the age of 18 years: the safety and efficacy in children have not been established.

ENABLEX should be used with caution in patients with controlled narrow-angle glaucoma.

Special precautions: ENABLEX should be administered with caution to patients with 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 (see CONTRAINDICATIONS).

Effects of other medicinal products on ENABLEX: ENABLEX metabolism is primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4. Therefore, inhibitors of these enzymes may alter ENABLEX pharmacokinetics (also see Pharmacokinetic properties). No major safety issues were noted in any of the clinical studies and no treatment-related serious adverse events were observed.

CYP2D6 inhibitors: No special dosing requirements are necessary in the presence of CYP2D6 inhibitors.

CYP3A4 inhibitors: In patients receiving medicines that are moderate CYP3A4 inhibitors such as fluconazole and erythromycin, the recommended starting dose is 7,5 mg daily. The dose may be titrated to 15 mg daily to obtain an improved clinical response provided the dose is well tolerated. However, caution should be exercised.

Effects of ENABLEX on other medicinal products: Caution should be exercised when ENABLEX is used concomitantly with medications that are predominantly metabolised by CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine, or tricyclic antidepressants such as imipramine. Because there is a potential for increased exposure to these substrates, physicians may consider reducing the dose of concomitantly administered medicines that are CYP2D6 substrates.

CYP3A4 substrates: ENABLEX had no clinically relevant effect on the exposure of the CYP3A4 substrate midazolam and had no effect on the pharmacokinetics of the oral contraceptives levonorgestrel or ethinylestradiol.

Other medicinal products: Standard therapeutic prothrombin time monitoring for warfarin should be continued. The effect of a single dose of warfarin on prothrombin time was not altered when co-administered with ENABLEX. Standard therapeutic drug monitoring for digoxin should be continued. ENABLEX (30 mg once daily) co-administered with digoxin at steady state resulted in a small but potentially clinically significant increase in digoxin exposure (AUC: 16 %; C max : 20 %).

Use in pregnancy: There are no studies of ENABLEX in pregnant women. ENABLEX should not be used during pregnancy.

Use in lactation: ENABLEX is excreted into the milk of rats. ENABLEX should not be used in breastfeeding women.

Studies on the effects of ENABLEX on the ability to drive and use machines have not been performed. Nevertheless, caution should be exercised when driving or using machines.

Very common adverse drug reactions (ADRs) were dry mouth and constipation. However, the patient discontinuation rates due to these adverse drug reactions were low (dry mouth: 0 % and 0,9 % for the 7,5 mg and 15 mg dose, respectively, constipation: 0,6 % and 1,2 % for the 7,5 mg and 15 mg dose, respectively). In the pivotal clinical trials with doses of 7,5 mg and 15 mg ENABLEX, ADRs were reported as presented in the table below. Most were mild or moderate and did not result in discontinuation in the majority of the patients. The incidence of serious adverse events with 7,5 mg and 15 mg ENABLEX once daily was similar to placebo.

No overdosages were recorded in the ENABLEX clinical development programme. However, overdosage with ENABLEX can potentially lead to severe anticholinergic effects and should be treated accordingly. Therapy should be aimed at reversing the anticholinergic symptoms under careful medical supervision. The use of medicines such as physostigmine can assist in reversing such symptoms.