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Pronunciation
(dar i FEN a sin)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of symptoms of bladder overactivity (urge incontinence, urgency, and frequency)
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects and developmental delay were observed in some animal studies. There are no adequate and well-controlled studies in pregnant women; should be used only if potential benefit outweighs possible risk to the fetus.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Although human data are not available, darifenacin is excreted in the breast milk in animals.
Contraindications
Hypersensitivity to darifenacin or any component of the formulation; uncontrolled narrow-angle glaucoma; urinary retention, paralytic ileus, GI or GU obstruction
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: May cause drowsiness and/or blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Heat prostration: May occur in the presence of increased environmental temperature; use caution in hot weather and/or exercise.
Disease-related concerns:
• Gastrointestinal disease: Use with caution in patients with decreased GI motility, constipation, hiatal hernia, reflux esophagitis, and ulcerative colitis; may decrease GI motility.
• Glaucoma: In patients with controlled narrow-angle glaucoma, darifenacin should be used with extreme caution and only when the potential benefit outweighs risks of treatment.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage limitation is required in moderate hepatic impairment (Child-Pugh class B). Not recommended for use in severe hepatic impairment (Child-Pugh class C).
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may decrease GI motility.
• Prostatic hyperplasia/bladder outlet obstruction: Use with caution in patients with prostatic hyperplasia (nonobstructive) or clinically-significant bladder outlet obstruction; may increase risk of urinary retention.
Concurrent drug therapy issues:
• High potential for interactions: Use with caution in patients taking strong CYP3A4 inhibitors (see Drug Interactions); dosage limitation of darifenacin is required.
Adverse Reactions
>10%: Gastrointestinal: Xerostomia (19% to 35%), constipation (15% to 21%)
1% to 10%:
Cardiovascular: Hypertension (≥1%), peripheral edema (≥1%)
Central nervous system: Headache (7%), dizziness (<2%), pain (≥1%)
Dermatological: Dry skin (≥1%), pruritus (≥1%), rash (≥1%)
Gastrointestinal: Dyspepsia (3% to 8%), abdominal pain (2% to 4%), nausea (2% to 4%), vomiting (≥1%), weight gain (≥1%)
Genitourinary: Urinary tract infection (4% to 5%), vaginitis (≥1%), urinary retention (acute)
Neuromuscular & skeletal: Weakness (<3%), arthralgia (≥1%), back pain (≥1%)
Ocular: Dry eyes (2%), abnormal vision (≥1%)
Respiratory: Bronchitis (≥1%), pharyngitis (≥1%), rhinitis (≥1%), sinusitis (≥1%)
Miscellaneous: Flu-like syndrome (1% to 3%)
Postmarketing and/or case reports: Angioedema, confusion, hallucinations, hypersensitivity reactions, palpitation
Metabolism/Transport Effects
Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (moderate), CYP3A4 (weak)
Drug Interactions
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
Cannabinoids: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoids. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Propafenone: May increase the serum concentration of CYP2D6 Inhibitors (Moderate). Risk C: Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Risk D: Consider therapy modification
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Risk D: Consider therapy modification
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Darifenacin serum concentration may be decreased by St John's wort (avoid concurrent use.)
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Mechanism of Action
Selective antagonist of the M3 muscarinic (cholinergic) receptor subtype. Blockade of the receptor limits bladder contractions, reducing the symptoms of bladder irritability/overactivity (urge incontinence, urgency and frequency).
Pharmacodynamics/Kinetics
Distribution: Vdss: ~163 L
Protein binding: ~98% (primarily alpha1-acid glycoprotein)
Metabolism: Hepatic, via CYP3A4 (major) and CYP2D6 (minor)
Bioavailability: 15% to 19%
Half-life elimination: ~13-19 hours
Time to peak, plasma: ~7 hours
Excretion: As metabolites (inactive); urine (60%), feces (40%)
Dosage
Oral: Adults: Initial: 7.5 mg once daily. If response is not adequate after a minimum of 2 weeks, dosage may be increased to 15 mg once daily.
Dosage adjustment with concomitant potent CYP3A4 inhibitors (eg, azole antifungals, erythromycin, isoniazid, protease inhibitors): Daily dosage should not exceed 7.5 mg/day
Dosage adjustment in renal impairment: No adjustment required.
Dosage adjustment in hepatic impairment:
Moderate impairment (Child-Pugh class B): Daily dosage should not exceed 7.5 mg/day
Severe impairment (Child-Pugh class C): Has not been evaluated; use is not recommended
Administration: Oral
Tablet should be taken with liquid and swallowed whole; do not chew, crush, or split tablet. May be taken without regard to food.
Dietary Considerations
May be taken without regard to meals, with or without food.
Patient Education
Swallow tablet whole. May cause headache, dizziness, nervousness, sleepiness, abdominal discomfort, diarrhea, constipation, dry mouth, nausea, or vomiting. Report back pain, muscle spasms, alteration in gait, or numbness of extremities; unresolved or persistent constipation, diarrhea, or vomiting; symptoms of upper respiratory infection or flu; or difficulty urinating, pain on urination, or abdominal pain.
Geriatric Considerations
There is a trend for decreased clearance of darifenacin with age, though no change in dose is recommended. The selectivity of darifenacin for the M3 receptor on the bladder may offer an advantage (less CNS and cardiovascular effects) over other anticholinergic agents used in the treatment of overactive bladder.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Prolonged xerostomia may contribute to discomfort and dental disease (eg, caries, periodontal disease, and oral candidiasis).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Concomitant use with acetylcholinesterase inhibitors will mitigate their clinical effects. Concomitant use with psychotropic agents may produce additive anticholinergic effects. Darifenacin may increase levels of fluoxetine, mirtazapine, nefazodone, paroxetine, risperidone, thioridazine, TCAs, and venlafaxine.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, extended release, oral:
Enablex®: 7.5 mg, 15 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Enablex)
7.5 mg (30): $155.99
15 mg (30): $163.99
References
Croom KF and Keating GM, “Darifenacin in the Treatment of Overactive Bladder,” Drugs Aging, 2004, 21(13):885-92.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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