(dar i FEN a sin)
Management of symptoms of bladder overactivity (urge incontinence, urgency, and frequency)
Hypersensitivity to darifenacin or any component of the formulation; uncontrolled narrow-angle glaucoma; urinary retention, paralytic ileus, GI or GU obstruction
Symptoms of bladder overactivity: Oral: 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, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, nefazodone): Daily dosage should not exceed 7.5 mg daily
Refer to adult dosing.
No dosage adjustment necessary.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Daily dosage should not exceed 7.5 mg daily
Severe impairment (Child-Pugh class C): Has not been evaluated; use is not recommended
Tablet should be taken with liquid and swallowed whole; do not chew, crush, or split tablet. May be taken without regard to food.
May be taken without regard to meals, with or without food.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Enablex: 7.5 mg, 15 mg
Generic: 7.5 mg, 15 mg
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Monitor therapy
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. 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. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose. Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
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. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Propafenone: May increase the serum concentration of CYP2D6 Inhibitors (Moderate). Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. 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. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
>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: Pruritus ( ≥1%), skin rash ( ≥1%), xeroderma ( ≥1%)
Endocrine & metabolic: Weight gain ( ≥1%)
Gastrointestinal: Dyspepsia (3% to 8%), abdominal pain (2% to 4%), nausea (2% to 4%), vomiting ( ≥1%)
Genitourinary: Urinary tract infection (4% to 5%), vaginitis ( ≥1%), urinary retention (acute)
Neuromuscular & skeletal: Weakness (<3%), arthralgia ( ≥1%), back pain ( ≥1%)
Ophthalmic: Dry eye syndrome (2%), visual disturbance ( ≥1%)
Respiratory: Flu-like symptoms (1% to 3%), bronchitis ( ≥1%), pharyngitis ( ≥1%), rhinitis ( ≥1%), sinusitis ( ≥1%)
Postmarketing and/or case reports (Limited to important or life-threatening): Anaphylaxis, angioedema, confusion, erythema multiforme, granuloma (annulare), hallucination, hypersensitivity reaction
Unbound darifenacin exposure was estimated to be 4.7-fold higher in subjects with moderate hepatic impairment.
Clearance decreases approximately 6% per decade relative to a median age of 44 years. Exposure at steady state was 12% to 19% higher in subjects 45 to 65 years of age compared with those 18 to 44 years of age.
Cmax and AUC were approximately 57% to 79% and 61%to 73% higher, respectively, in women than in men.
Concerns related to adverse effects:
- Angioedema: Cases of angioedema involving the face, lips, tongue, and/or larynx have been reported during treatment; some cases have occurred after the first dose. May be life-threatening. Immediately discontinue and institute supportive care if tongue, hypopharynx, or larynx is involved.
- CNS effects: Central nervous system effects have been reported (eg, headache, confusion, hallucinations, somnolence); monitor, particularly at treatment initiation or dose increase, reduce dose or discontinue if necessary. 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.
C
Adverse events have been observed in animal reproduction studies.
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).
Vdss: ~163 L
Hepatic, via CYP3A4 (major) and CYP2D6 (minor)
Urine (60%), feces (40%); as metabolites (inactive)
Plasma: ~7 hours
~13-19 hours
~98% (primarily alpha1-acid glycoprotein)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience heartburn or dry mouth. Have patient report immediately to prescriber severe dizziness, passing out, confusion, severe constipation, lack of sweat, severe nausea, severe vomiting, or edema of hands or feet (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.