is very Darifenacin Hydrobromide Class: Genitourinary Smooth Muscle Relaxants Chemical Name: (S)-1-[2-(2,3-Dihydro-5-benzofuranyl)ethyl]-α,α-diphenyl-3-pyrrolidineacetamide Molecular Formula: C 28 H 30 N 2 O 2 CAS Number: 133099-04-4 Brands: Enablex Overview Side Effects Dosage Professional Interactions More Pregnancy Warnings User Reviews Drug Images Support Group Q & A Pricing & Coupons Introduction Genitourinary antispasmodic agent; an antimuscarinic agent. 1 Uses for Darifenacin Hydrobromide Overactive Bladder Relief of symptoms associated with voiding (e.g., urge urinary incontinence, urgency, frequency). 1 Extended-release darifenacin (15 mg once daily) may be as effective as immediate-release oxybutynin (5 mg 3 times daily). 5 Slideshow Botox For Beginners: What You Need To Know Darifenacin Hydrobromide Dosage and Administration Administration Oral Administration Administer orally once daily with liquids without regard to meals. 1 Swallow tablets whole; do not chew, divide, or crush. 1 Dosage Available as darifenacin hydrobromide; dosage expressed in terms of darifenacin. 1 Adults Overactive Bladder Oral Initially, 7.5 mg once daily. 1 May increase after 2 weeks to 15 mg once daily according to response. 1 Prescribing Limits Adults Overactive Bladder Oral Maximum 15 mg daily. 1 Special Populations Hepatic Impairment No dosage adjustment required in patients with mild hepatic impairment (Child-Pugh class A). 1 Maximum 7.5 mg daily in patients with moderate hepatic impairment (Child-Pugh class B). 1 Use not recommended in patients with severe hepatic impairment (Child-Pugh class C). 1 (See Distribution: Special Populations, under Pharmacokinetics.) Renal Impairment No dosage adjustment required. 1 8 Geriatric Patients No dosage adjustment required. 1 Cautions for Darifenacin Hydrobromide Contraindications Urinary retention, gastric retention, or uncontrolled angle-closure glaucoma or risk of these conditions. 1 Known hypersensitivity to darifenacin or any ingredient in the formulation. 1 Warnings/Precautions Major Toxicities GU Effects Severe acute urinary retention requiring treatment reported in some patients receiving higher than recommended dosages (e.g., 30 mg daily) and in patients with detrusor hyperreflexia secondary to a stroke, benign prostatic hypertrophy, or irritable bowel syndrome. 1 Acute urinary retention requiring bladder catheterization for 1 2 days also reported at therapeutic dosages. 1 Use with caution in patients with clinically important bladder outflow obstruction. 1 General Precautions Decreased GI Motility May decrease GI motility; use with caution in patients with severe constipation, ulcerative colitis, or myasthenia gravis. 1 Severe constipation reported. 1 Risk of gastric retention; use with caution in patients with obstructive GI disorders. 1 Controlled Angle-closure Glaucoma In patients being treated for angle-closure glaucoma, use only if potential benefits outweigh risks. 1 (See Contraindications under Cautions.) Specific Populations Pregnancy Category C. 1 Lactation Distributed into milk in rats; not known whether distributed into human milk. 1 Use caution. 1 Pediatric Use Safety and efficacy not established in pediatric patients. 1 Geriatric Use No substantial differences in safety and efficacy relative to younger adults. 1 (See Geriatric Patients under Dosage and Administration and see Elimination: Special Populations, under Pharmacokinetics.) Hepatic Impairment Use not evaluated and not recommended in patients with severe hepatic impairment (Child-Pugh class C). 1 (See Hepatic Impairment under Dosage and Administration and see Distribution: Special Populations, under Pharmacokinetics.) Common Adverse Effects Dry mouth, constipation. 1 Interactions for Darifenacin Hydrobromide Metabolized principally by CYP2D6 and CYP3A4. 1 May inhibit CYP2D6 and CYP3A4; not expected to inhibit CYP1A2 and CYP2C9. 1 Drugs Affecting Hepatic Microsomal Enzymes Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma darifenacin concentrations). 1 7 Do not exceed 7.5 mg daily when used concomitantly with potent inhibitors of CYP3A4. 1 No dosage adjustment required when used concomitantly with moderate CYP3A4 inhibitors. 1 (See Specific Drugs under Interactions.) Inhibitors of CYP2D6: Potential pharmacokinetic interaction (increased plasma darifenacin concentrations). 1 However, no dosage adjustment required. 1 Mixed inhibitors of CYP isoenzymes: Potential pharmacokinetic interaction (increased plasma darifenacin concentrations). 1 However, no dosage adjustment required. 8 Inducers of CYP3A4: Potential pharmacokinetic interaction 1 (altered plasma darifenacin concentrations). 1 8 Drugs Metabolized by Hepatic Microsomal Enzymes Substrates of CYP3A4: Potential pharmacokinetic interaction (increased plasma substrate concentrations). 1 Substrates of CYP2D6: Potential pharmacokinetic interaction (increased plasma substrate concentrations). 1 Caution advised when used concomitantly with CYP2D6 substrates that have a narrow therapeutic index. 1 Substrates of CYP1A2 or CYP2C9: Pharmacokinetic interaction not expected at therapeutic dosages. 8 Drugs Affected by GI Motility Potential pharmacokinetic interaction (altered absorption because of decreased GI motility). 1 (See Decreased GI Motility under Cautions.) Specific Drugs Drug Interaction Comments Anticholinergic agents Possible additive anticholinergic effects (e.g., decreased GI motility; altered absorption of other drugs) 1 Antidepressants, tricyclics Possible increased concentrations of tricyclic antidepressant 1 Use concomitantly with caution 1 Cimetidine Increased plasma darifenacin concentrations 1 No dosage adjustment required 1 Clarithromycin Possible increased plasma darifenacin concentrations 1 Do not exceed a darifenacin dosage of 7.5 mg daily 1 Digoxin Increased digoxin exposure 1 Continue routine monitoring of digoxin therapy 1 Diltiazem Possible increased plasma darifenacin concentrations 1 No dosage adjustment required 1 Erythromycin Increased plasma darifenacin concentrations 1 No dosage adjustment required 1 Flecainide Possible increased flecainide concentrations 1 Use concomitantly with caution 1 Fluconazole Increased plasma darifenacin concentrations 1 No dosage adjustment required 1 Hormonal contraceptives Pharmacokinetic interaction unlikely with oral contraceptives containing ethinyl estradiol and levonorgestrel 1 Imipramine Increased plasma concentrations of imipramine and desipramine 1 Itraconazole Possible increased plasma darifenacin concentrations 1 Do not exceed a darifenacin dosage of 7.5 mg daily 1 Ketoconazole Increased plasma darifenacin concentrations 1 Do not exceed a darifenacin dosage of 7.5 mg daily 1 Midazolam Increased midazolam concentrations 1 Nefazodone Possible increased plasma darifenacin concentrations 1 Do not exceed a darifenacin dosage of 7.5 mg daily 1 Nelfinavir Possible increased plasma darifenacin concentrations 1 Do not exceed a darifenacin dosage of 7.5 mg daily 1 Paroxetine Increased plasma darifenacin concentrations 1 No dosage adjustment required 1 Ritonavir Possible increased plasma darifenacin concentrations 1 Do not exceed a darifenacin dosage of 7.5 mg daily 1 Thioridazine Possible increased thioridazine concentrations 1 Use concomitantly with caution 1 Verapamil Possible increased plasma darifenacin concentrations 1 No dosage adjustment required 1 Warfarin No substantial effect on PT 1 Continue routine monitoring of PT 1 Darifenacin Hydrobromide Pharmacokinetics Absorption Bioavailability Mean oral bioavailability at steady-state is approximately 15 or 19% for the 7.5- or 15-mg tablets, respectively. 1 7 Peak plasma concentrations achieved approximately 7 hours after multiple dosing. 1 Onset Symptomatic improvement (i.e., reduction in number of urge incontinence episodes) observed within first 2 weeks of therapy. 1 6 Food Food does not affect darifenacin pharmacokinetics. 1 Special Populations Darifenacin exposure is 40 or 90% higher in CYP2D6 heterozygote-extensive metabolizers or poor metabolizers, respectively, and 56% lower in Japanese males. 7 Distribution Extent Distributed into milk in rats; not known whether distributed into human milk. 1 Plasma Protein Binding Approximately 98% (mainly to α 1 -acid glycoprotein). 1 Special Populations In patients with moderate hepatic impairment (Child-Pugh class B), decreased protein binding resulting in increased darifenacin exposure observed. 1 (See Hepatic Impairment under Dosage and Administration.) Elimination Metabolism Extensively metabolized in the liver, mainly via CYP2D6 and CYP3A4. 1 Elimination Route Excreted in urine (60%) and in feces (40%); unchanged drug accounts for about 3% of recovered radioactivity. 1 Half-life Approximately 13 19 hours following long-term administration. 1 Special Populations In patients with poor metabolizer CYP2D6 phenotypes (approximately 7% of Caucasians and 2% of African Americans), darifenacin is metabolized principally via CYP3A4; decreased clearance observed. 1 7 Steady-state plasma concentrations following 15-mg daily dosage approximately 1.7 1.9 times higher in poor metabolizers than in extensive metabolizers. 1 In geriatric patients, possible decreased clearance (decreases about 6% per decade beginning at 44 years of age). 1 In patients with renal impairment, no clear relationship between extent of impairment and darifenacin clearance observed in patients with Cl cr 10 136 mL/minute. 1 (See Renal Impairment under Dosage and Administration.) Stability Storage Oral Extended-release Tablets 25 C (may be exposed to 15 30 C). 1 Protect from light. 1 Actions Potent and selective antimuscarinic agent. 1 Inhibits binding of acetylcholine to muscarinic receptors in cholinergically innervated organs. 8 Demonstrates substantially greater binding affinity for muscarinic M 3 receptors (which are involved in contraction of detrusor muscle of bladder and GI smooth muscle, saliva production, and iris sphincter function) in vitro than for other muscarinic receptor subtypes. 1 3 8 Exhibits functional selectivity for urinary bladder over secretory (e.g., salivary) glands. 2 3 Increases bladder capacity and diminishes frequency of unstable contractions of detrusor muscle in patients with involuntary detrusor contractions. 1 Advice to Patients Risk of constipation, urinary retention, blurred vision, and heat prostration (when used in a hot environment). 1 4 Use caution when driving or performing dangerous activities until effects on vision are known. 4 Importance of taking tablets with liquids and swallowing whole; do not chew, divide, or crush. 1 4 If a dose is skipped, resume therapy the next day; do not take 2 doses in the same day. 4 Importance of reading manufacturer s patient information leaflet before initiating therapy. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. 1 Importance of advising patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Darifenacin Hydrobromide Routes Dosage Forms Strengths Brand Names Manufacturer Oral Tablets, extended-release 7.5 mg (of darifenacin) Enablex Novartis 15 mg (of darifenacin) Enablex Novartis AHFS DI Essentials. Copyright 2017, Selected Revisions June 1, 2005. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Novartis. Enablex (darifenacin hydrobromide) extended-release tablets prescribing information. East Hanover, NJ; 2004 Dec. 2. Miyamae K, Yoshida M, Murakami S et al. Pharmacological effects of darifenacin on human isolated urinary bladder. Pharmacology . 2003; 69:205-11. [PubMed 14624061] 3. Croom KF, Keating GM. Darifenacin in the treatment of overactive bladder. Drugs Aging . 2004; 21:885-92. [PubMed 15493952] 4. Novartis. Enablex (darifenacin hydrobromide) extended-release tablets patient information. East Hanover, NJ; 2004 Dec. 5. Zinner N, Tuttle J, and Marks L. Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist, compared with oxybutynin in the treatment of patients with overactive bladder. Joint Meeting of the International Continence Society and the International Urogynecological Association. Paris: 2004. Abstract No. 378. From The International Continence Society website () 6. Haab F, Stewart L, and Dwyer P. Darifenacin, an M 3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol . 2004; 45:420-9. [PubMed 15041104] 7. Kerbusch T, Wahlby U, Milligan PA et al. Population pharmacokinetic modeling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavailability. Br J Clin Pharmacol . 2003; 56:639-52. [PubMed 14616424] 8. Novartis, East Hanover, NJ: Personal communication. 9. Steers W, Corcos J, Foote J et al. An investigation of dose titration with darifenacin, an M3-selective receptor antagonist. BJU Int . 2005; 95:580-6. [PubMed 15705084] Next Interactions Print this page Add to My Med List More about darifenacin Side Effects During Pregnancy Dosage Information Drug Images Drug Interactions Support Group Pricing & Coupons En Español 19 Reviews Add your own review/rating Drug class: urinary antispasmodics Consumer resources Darifenacin Darifenacin (Advanced Reading) Professional resources Darifenacin (FDA) Darifenacin (Wolters Kluwer) Other brands: Enablex Related treatment guides Overactive Bladder Urinary Incontinence} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturers Par Pharmaceutical, Inc. Teva Pharmaceuticals USA, Inc. Torrent Pharmaceuticals Limited Aurobindo Pharma Limited Jubilant Cadista Pharmaceuticals Inc. Macleods Pharmaceuticals Limited More... Drug Class Urinary antispasmodics Related Drugs Overactive Bladder oxybutynin , Myrbetriq , VESIcare , Ditropan , tolterodine , Toviaz , solifenacin , mirabegron , Detrol , Botox , trospium , Enablex , More... Urinary Incontinence oxybutynin , VESIcare , Ditropan , tolterodine , Toviaz , solifenacin , Detrol , trospium , Enablex , Ditropan XL , fesoterodine , Detrol LA , More... Darifenacin Rating 19 User Reviews 6.3 /10 19 User Reviews 6.3 Rate it! Darifenacin Images Darifenacin systemic 7.5 mg (base) (C170 ) View all images} } take the plunge
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