Darifenacin 15 mg Tablet, Extended Release, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Cholinergic Muscarinic Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Darifenacin is used to treat an overactive bladder (a bladder condition that causes sudden urges to urinate that may be hard to control). Darifenacin is in a class of medications called antimuscarinics. It works by relaxing the bladder muscles.
Read the full MedlinePlus article ↗- Your bladder has receptors called M3 receptors that trigger the muscle to squeeze. With overactive bladder, those squeezes happen too often or too forcefully. Darifenacin blocks th...
- What exactly is darifenacin doing to help my bladder?
- No — this one really matters. Darifenacin is an extended-release tablet, which means it's specially designed to release the medicine slowly over the day. If you chew, crush, or spl...
- Can I cut or crush the tablet if it's hard to swallow?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Darifenacin — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
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Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.397 | $11.91 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.8931 | $26.79 / 30 tablets |
| Medicare drug plans payPart D · Q2 2026 | $2.34 | $70.17 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Darifenacin 15 mg 16571-0768-03 | Rising | 30 tablets | $0.397 | AB | Availability likely | — |
| Darifenacin 15 mgthis 33342-0277-07 | Macleods | 30 tablets | $0.397 | AB | Availability likely | — |
| Darifenacin 15 mg 69097-0432-02 | Cipla | 30 tablets | $0.397 | AB | Availability likely | — |
| Darifenacin 15 mg 13668-0203-05 | Torrent | 500 tablets | — | AB | FDA listed | — |
| Darifenacin 15 mg 46708-0224-08 | Alembic | 8 tablets | — | AB | FDA listed | — |
| Darifenacin 15 mg 52605-0068-10 | POLYGEN | 1000 tablets | — | AB | Discontinued | — |
| Darifenacin 15 mg 62332-0224-08 | Alembic | 8 tablets | — | AB | FDA listed | — |
| Darifenacin 15 mg 65862-0862-05 | Aurobindo | 500 tablets | — | AB | FDA listed | — |
| Darifenacin 15 mg 72162-2571-03 | Bryant | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 33342-0277-07 You're viewing this | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (33342-277-07) | $0.3971 / ea | $11.91 | 2017-07-29 | Active |
| 33342-0277-10 | 90 TABLET, EXTENDED RELEASE in 1 BOTTLE (33342-277-10) | $1.38 / ea | $124.21 | 2017-07-29 | Active |
| 33342-0277-12 | 10 BLISTER PACK in 1 CARTON (33342-277-12) / 10 TABLET, EXTENDED RELEASE in 1 BLISTER PACK | — | — | 2017-07-29 | Active |
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.3971 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 33342-0277-07?
What is the difference between NDC 33342-0277-07 and NDC 33342-0277-10?
What NDC number is used to bill for this package of Darifenacin 15 mg Tablet, Extended Release?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS & USAGE Darifenacin is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. Darifenacin extended-release tablet is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE & ADMINISTRATION The recommended starting dose of darifenacin is 7.5 mg orally once daily. Based upon individual response, the dose may be increased to 15 mg once daily, as early as two weeks after starting therapy. Darifenacin should be taken orally once daily with water.
Darifenacin 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 (for example, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone), the daily dose of darifenacin should not exceed 7.5 mg. Darifenacin is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) [see Warnings & Precautions ( 5.6 ), Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )].
The recommended starting dose of darifenacin extended-release tablets is 7.5 mg once daily. Based upon individual response, the dose may be increased to 15 mg once daily, as early as two weeks after starting therapy ( 2 ) The daily dose of darifenacin should not exceed 7.5 mg in the following patients: • Patients with moderate hepatic impairment (Child- Pugh B) ( 2 , 8.6 ) • Patients taking potent CYP3A4 inhibitors ( 2 , 7.1 ) Darifenacin is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) ( 2 , 8.6 ) Darifenacin may be taken with or without food.
The tablet should be swallowed whole with water and not chewed, divided or crushed ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS & STRENGTHS Darifenacin extended-release tablets 7.5 mg are white-colored, round, bi-convex, film coated and are debossed with “L48” on one side and plain on the other side. Darifenacin extended-release tablets 15 mg are light peach-colored, round, bi-convex, film coated and are debossed with “L49” on one side and plain on the other side. Extended-release tablets 7.5 mg and 15 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Darifenacin is contraindicated in patients with, or at risk for, the following conditions: • urinary retention • gastric retention, or • uncontrolled narrow-angle glaucoma. Darifenacin is contraindicated in patients with, or at risk for, the following conditions ( 4 ): • urinary retention, • gastric retention, or • uncontrolled narrow-angle glaucoma.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Darifenacin should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention ( 5.1 ) • Darifenacin should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention ( 5.2 ) • Darifenacin should be used with caution in patients being treated for narrow-angle glaucoma and only where the potential benefits outweigh the risks ( 5.3 ) • Central Nervous System Effects: Somnolence has been reported with darifenacin.
Advise patients not to drive or operate heavy machinery until they know how darifenacin affects them ( 5.5 )
5.1Risk of Urinary Retention Darifenacin should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.
5.2Decreased Gastrointestinal Motility Darifenacin should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention. Darifenacin, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as severe constipation, ulcerative colitis, and myasthenia gravis.
5.3Controlled Narrow-Angle Glaucoma Darifenacin should be used with caution in patients being treated for narrow-angle glaucoma and only where the potential benefits outweigh the risks.
5.4Angioedema Angioedema of the face, lips, tongue, and/or larynx have been reported with darifenacin. In some cases angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, darifenacin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.
5.5Central Nervous System Effects Darifenacin is associated with anticholinergic central nervous system (CNS) effects [see Adverse Reactions ( 6.2 )]. A variety of CNS anticholinergic effects have been reported, including headache, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose.
Advise patients not to drive or operate heavy machinery until they know how darifenacin affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.
5.6Patients with Hepatic Impairment The daily dose of darifenacin should not exceed 7.5 mg for patients with moderate hepatic impairment (Child-Pugh B). darifenacin has not been studied in patients with severe hepatic impairment (Child-Pugh C) and therefore is not recommended for use in this patient population [see Dosage and Administration ( 2 ) Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most frequently reported adverse reactions (greater than 3%) for darifenacin are: constipation, dry mouth, headache, dyspepsia, nausea, urinary tract infection, accidental injury, and flu symptoms ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of darifenacin was evaluated in controlled clinical trials in a total of 8,830 patients, 6,001 of whom were treated with darifenacin. Of this total, 1,069 patients participated in three, 12-week, randomized, placebo-controlled, fixed-dose efficacy and safety studies (Studies 1, 2 and 3).
Of this total, 337 and 334 patients received darifenacin 7.5 mg daily and 15 mg daily, respectively. In all long-term trials combined, 1,216 and 672 patients received treatment with darifenacin for at least 24 and 52 weeks, respectively. In Studies 1, 2 and 3 combined, the serious adverse reactions to darifenacin were urinary retention and constipation.
In Studies 1, 2 and 3 combined, dry mouth leading to study discontinuation occurred in 0%, 0.9%, and 0% of patients treated with darifenacin 7.5 mg daily, darifenacin 15 mg daily and placebo, respectively. Constipation leading to study discontinuation occurred in 0.6%, 1.2%, and 0.3% of patients treated with darifenacin 7.5 mg daily, darifenacin 15 mg daily and placebo, respectively. Table 1 lists the rates of identified adverse reactions, derived from all reported adverse events in 2% or more of patients treated with 7.5 mg or 15 mg darifenacin, and greater than placebo in Studies 1, 2 and 3.
In these studies, the most frequently reported adverse reactions were dry mouth and constipation. The majority of the adverse reactions were mild or moderate in severity and most occurred during the first two weeks of treatment. Table 1: Incidence of Identified Adverse Reactions, Derived from All Adverse Events Reported in greater than or equal to 2% of Patients Treated with Darifenacin Extended-Release Tablets and More Frequent with darifenacin than with Placebo in Studies 1, 2, and 3 Body System Adverse Reaction % of Subjects Darifenacin 7.5 mg N= 337 Darifenacin 15 mg N=334 Placebo N=388 Digestive Dry Mouth 20.2 35.3
8.2Constipation 14.8 21.3
6.2Dyspepsia 2.7 8.4
2.6Abdominal Pain 2.4 3.9
0.5Nausea 2.7 1.5
1.5Diarrhea 2.1 0.9
1.8Urogenital Urinary Tract Infection 4.7 4.5
2.6Nervous Dizziness 0.9 2.1
1.3Body as a Whole Asthenia 1.5 2.7
1.3Eye Dry Eyes 1.5 2.1
0.5Other adverse reactions reported by 1% to 2% of darifenacin -treated patients include: abnormal vision, accidental injury, back pain, dry skin, flu syndrome, hypertension, vomiting, peripheral edema, weight gain, arthralgia, bronchitis, pharyngitis, rhinitis, sinusitis, rash, pruritus, urinary tract disorder and vaginitis. Study 4 was a randomized, 12-week, placebo-controlled, dose-titration regimen study in which darifenacin was administered in accordance with dosing recommendations [see Dosage and Administration ( 2 )].
All patients initially received placebo or darifenacin 7.5 mg daily, and after two weeks, patients and physicians were allowed to adjust upward to darifenacin 15 mg if needed. In this study, the most commonly reported adverse reactions were also constipation and dry mouth. Table 2 lists the identified adverse reactions, derived from all adverse events reported in greater than 3% of patients treated with darifenacin and greater than placebo.
Table 2: Number (%) of Adverse Reactions, Derived from All Adverse Events Reported in greater than 3% of Patients Treated with Darifenacin Extended-Release Tablets, and More Frequent with Darifenacin tha…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Caution should be taken when darifenacin is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window, such as flecainide, thioridazine and tricyclic antidepressants ( 7.2 ) • The concomitant use of darifenacin with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects of gastrointestinal motility ( 7.3 )
7.1CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. The daily dose of darifenacin should not exceed 7.5 mg when co-administered with potent CYP3A4 inhibitors (for example, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone). No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (for example, erythromycin, fluconazole, diltiazem and verapamil) [see Dosage and Administration ( 2 ) and Clinical Pharmacology ( 12.3 )].
7.2CYP2D6 Inhibitors No dosing adjustments are recommended in the presence of CYP2D6 inhibitors (for example, paroxetine, fluoxetine, quinidine and duloxetine) [see Clinical Pharmacology ( 12.3 )].
7.3CYP2D6 Substrates Caution should be taken when darifenacin is used concomitantly with medications that are predominantly metabolized by CYP2D6 and which have a narrow therapeutic window (for example, flecainide, thioridazine and tricyclic antidepressants) [see Clinical Pharmacology ( 12.3 )].
7.4CYP3A4 Substrates Darifenacin (30 mg daily) did not have a significant impact on midazolam (7.5 mg) pharmacokinetics [see Clinical Pharmacology ( 12.3 )].
7.5Combination oral contraceptives Darifenacin (10 mg three times daily) had no effect on the pharmacokinetics of the combination oral contraceptives containing levonorgestrel and ethinyl estradiol [see Clinical Pharmacology ( 12.3 )].
7.6Warfarin Darifenacin had no significant effect on prothrombin time when a single dose of warfarin 30 mg was co-administered with darifenacin (30 mg daily) at steady-state. Standard therapeutic prothrombin time monitoring for warfarin should be continued.
7.7Digoxin Darifenacin (30 mg daily) did not have a clinically relevant effect on the pharmacokinetics of digoxin (0.25 mg) at steady-state. Routine therapeutic drug monitoring for digoxin should be continued [see Clinical Pharmacology ( 12.3 )].
7.8Other Anticholinergic Agents The concomitant use of darifenacin with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to effects on gastrointestinal motility.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: Darifenacin should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus ( 8.1 ) • Nursing Mothers: It is not known whether darifenacin is excreted into human milk and therefore caution should be exercised before darifenacin is administered to a nursing woman ( 8.3 ) • Pediatric Use: The safety and effectiveness of darifenacin in pediatric patients have not been established ( 8.4 )
8.1Pregnancy Risk Summary There are no available data on darifenacin use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal studies, darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 and 28 times the maximum recommended human dose (MRHD) of 15 mg, respectively. Effects on embryofetal development were observed following administration of darifenacin during pregnancy (dilated ureter and/or kidney pelvis in rabbits at about 9 times the MRHD, post-implantation loss in rabbits at about 28 times, and delayed ossification in rats at about 59 times) and during pregnancy and lactation (developmental delays in rats at about 17 times the MRHD), which was associated with maternal toxicity (see Data).
Dystocia was observed in rat dams at about 17 times the MRHD. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Embryofetal development studies were conducted with oral darifenacin in female rats (0, 3, 10, and 50 mg/kg/day) and rabbits (0, 3, 10, and 30 mg/kg/day) during the period of organogenesis (gestation days 6 to 17 in the rat and gestation days 6 to 18 in the rabbit).
Darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 times and 28 times, respectively (doses up to 50 and 30 mg/kg/day, respectively) the maximum recommended human dose [MRHD] of 15 mg. At approximately 59 times the MRHD in pregnant rats, there was a delay in the ossification of the sacral and caudal vertebrae (associated with a decrease in maternal and pup body weight gains) which was not observed at an exposure approximately 13 times the AUC at the MRHD. At five times the AUC (3 mg/kg/day), there were no effects on dams or pups.
In pregnant rabbits, an exposure of darifenacin approximately 28 times the AUC at the MRHD of 15 mg (30 mg/kg/day) was shown to increase post-implantation loss (associated with decreased maternal body weight gain), with a no effect level at 10 mg/kg/day (9 times the AUC at the MRHD). Dilated ureter and/or kidney pelvis was also observed in offspring at this highest dose along with urinary bladder dilation consistent with the pharmacological action of darifenacin, with one case observed at the mid dose of 10 mg/kg/day (9 times the MRHD ).
No effect was observed at the lowest dose of 3 mg/kg/day ((approximately 2.8 times the AUC at the MRHD). A pre-and post-natal development study was conducted with oral darifenacin in female rats (0, 3, 10, and 50 mg/kg/day) throughout gestation and lactation. Decreased body weight gain and dystocia were observed in dams at 10 mg/kg/day (approximately 17 times the MRHD) and above.
Slight developmental delays (surface righting reflex, incisor eruption, eyelid opening, vaginal opening, preputial separation) were observed in pups at these doses. At 5 times the AUC at the MRHD (3 mg/kg/day), there were no effects on dams or pups.
8.2Lactation Risk Summary There are no data on the presence of darifenacin in human milk, the effects on the breastfed infant, or the effects of darifenacin on milk production. Darifenacin is present in rat milk [see Data]. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be cons…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on darifenacin use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal studies, darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 and 28 times the maximum recommended human dose (MRHD) of 15 mg, respectively. Effects on embryofetal development were observed following administration of darifenacin during pregnancy (dilated ureter and/or kidney pelvis in rabbits at about 9 times the MRHD, post-implantation loss in rabbits at about 28 times, and delayed ossification in rats at about 59 times) and during pregnancy and lactation (developmental delays in rats at about 17 times the MRHD), which was associated with maternal toxicity (see Data).
Dystocia was observed in rat dams at about 17 times the MRHD. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Embryofetal development studies were conducted with oral darifenacin in female rats (0, 3, 10, and 50 mg/kg/day) and rabbits (0, 3, 10, and 30 mg/kg/day) during the period of organogenesis (gestation days 6 to 17 in the rat and gestation days 6 to 18 in the rabbit).
Darifenacin was not teratogenic in rats and rabbits at plasma exposures of free drug (via AUC) up to 59 times and 28 times, respectively (doses up to 50 and 30 mg/kg/day, respectively) the maximum recommended human dose [MRHD] of 15 mg. At approximately 59 times the MRHD in pregnant rats, there was a delay in the ossification of the sacral and caudal vertebrae (associated with a decrease in maternal and pup body weight gains) which was not observed at an exposure approximately 13 times the AUC at the MRHD. At five times the AUC (3 mg/kg/day), there were no effects on dams or pups.
In pregnant rabbits, an exposure of darifenacin approximately 28 times the AUC at the MRHD of 15 mg (30 mg/kg/day) was shown to increase post-implantation loss (associated with decreased maternal body weight gain), with a no effect level at 10 mg/kg/day (9 times the AUC at the MRHD). Dilated ureter and/or kidney pelvis was also observed in offspring at this highest dose along with urinary bladder dilation consistent with the pharmacological action of darifenacin, with one case observed at the mid dose of 10 mg/kg/day (9 times the MRHD ).
No effect was observed at the lowest dose of 3 mg/kg/day ((approximately 2.8 times the AUC at the MRHD). A pre-and post-natal development study was conducted with oral darifenacin in female rats (0, 3, 10, and 50 mg/kg/day) throughout gestation and lactation. Decreased body weight gain and dystocia were observed in dams at 10 mg/kg/day (approximately 17 times the MRHD) and above.
Slight developmental delays (surface righting reflex, incisor eruption, eyelid opening, vaginal opening, preputial separation) were observed in pups at these doses. At 5 times the AUC at the MRHD (3 mg/kg/day), there were no effects on dams or pups.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of darifenacin in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use In the fixed-dose, placebo-controlled, clinical studies, 30 % of patients treated with darifenacin were over 65 years of age. No overall differences in safety or efficacy were observed between patients over 65 years (n = 207) and younger patients less than 65 years (n = 464). No dose adjustment is recommended for elderly patients [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )].
🆘 Overdosage ▾
10 OVERDOSAGE Overdosage with antimuscarinic agents, including darifenacin, can result in severe antimuscarinic effects. Treatment should be symptomatic and supportive. In the event of overdosage, ECG monitoring is recommended. Darifenacin has been administered in clinical trials at doses up to 75 mg (five times the maximum therapeutic dose) and signs of overdose were limited to abnormal vision.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Darifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play a role in cholinergically mediated functions, including contractions of the urinary bladder smooth muscle. In vitro studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M 3 receptor than for the other known muscarinic receptors (9- and 12-fold greater affinity for M3 compared to M 1 and M 5 , respectively, and 59-fold greater affinity for M 3 compared to both M 2 and M 4 ).
M 3 receptors are involved in contraction of human bladder.
12.2Pharmacodynamics In three cystometric studies performed in patients with involuntary detrusor contractions, increased bladder capacity was demonstrated by an increased volume threshold for unstable contractions and diminished frequency of unstable detrusor contractions after darifenacin treatment. These findings are consistent with an antimuscarinic action on the urinary bladder. Electrophysiology The effect of a six-day treatment of 15 mg and 75 mg darifenacin on QT/QTc interval was evaluated in a multiple-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) parallel-arm design study in 179 healthy adults (44% male, 56% female) aged 18 to 65.
Subjects included 18% poor metabolizers (PMs) and 82% extensive metabolizers (EMs). The QT interval was measured over a 24-hour period both predosing and at steady-state. The 75 mg darifenacin dose was chosen because this achieves exposure similar to that observed in CYP2D6 poor metabolizers administered the highest recommended dose (15 mg) of darifenacin in the presence of a potent CYP3A4 inhibitor.
At the doses studied, darifenacin did not result in QT/QTc interval prolongation at any time during the steady-state, while moxifloxacin treatment resulted in a mean increase from baseline QTcF of about 7.0 msec when compared to placebo. In this study, darifenacin 15 mg and 75 mg doses demonstrated a mean heart rate change of 3.1 and 1.3 bpm, respectively, when compared to placebo. However, in the clinical efficacy and safety studies, the change in median HR following treatment with darifenacin was no different from placebo.
12.3Pharmacokinetics Absorption After oral administration of darifenacin to healthy volunteers, peak plasma concentrations of darifenacin are reached approximately seven hours after multiple dosing and steady-state plasma concentrations are achieved by the sixth day of dosing. The mean (SD) steady-state time course of darifenacin 7.5 mg and 15 mg extended-release tablets is depicted in Figure 1. Figure 1 Mean (SD) Steady-State Darifenacin Plasma Concentration-Time Profiles for Darifenacin 7.5 mg and 15 mg in Healthy Volunteers Including Both CYP2D6 EMs and PMs* *Includes 95 EMs and 6 PMs for 7.5 mg; 104 EMs and 10 PMs for 15 mg.
A summary of mean (standard deviation, SD) steady-state pharmacokinetic parameters of darifenacin 7.5 mg and 15 mg extended-release tablets in EMs and PMs of CYP2D6 is provided in Table 3. Table 3: Mean (SD) Steady-State Pharmacokinetic Parameters from Darifenacin 7.5 mg and 15 mg Extended-Release Tablets Based on Pooled Data by Predicted CYP2D6 Phenotype Darifenacin 7.5 mg (N = 68 EM, 5 PM) Darifenacin 15 mg (N = 102 EM, 17 PM) AUC 24 (ng•h/mL) C max (ng/mL) C avg (ng/mL) T max (h) t1/2 (h) AUC 24 (ng•h/mL) C max (ng/mL) C avg (ng/mL) T max (h) t1/2 (h) EM 29.24 (15.47) 2.01 (1.04) 1.22 (0.64) 6.49 (4.19) 12.43 (5.64) a 88.90 (67.87) 5.76 (4.24) 3.70 (2.83) 7.61 (5.06) 12.05 (12.37) b PM 67.56 (13.13) 4.27 (0.98) 2.81 (0.55) 5.20 (1.79) 19.95 c - 157.71 (77.08) 9.99 (5.09) 6.58 (3.22) 6.71 (3.58) 7.40 d - a N = 25; b N = 8; c N = 2; d N = 1; AUC24 = Area under the plasma concentration versus time curve for 24h; C max = Maximum observed plasma concentration; Cavg = Average plasma concentration at steady-state; T max = Time of occurrence of C max ; t1/2 = Terminal elimination half-life.
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🧬 Mechanism of Action ▾
12.1Mechanism of Action Darifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play a role in cholinergically mediated functions, including contractions of the urinary bladder smooth muscle. In vitro studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M 3 receptor than for the other known muscarinic receptors (9- and 12-fold greater affinity for M3 compared to M 1 and M 5 , respectively, and 59-fold greater affinity for M 3 compared to both M 2 and M 4 ).
M 3 receptors are involved in contraction of human bladder.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Darifenacin extended-release tablets, 7.5 mg are white-colored, round, bi-convex, film coated and are debossed with “L48” on one side and plain on the other side. Bottle of 30 ....................................... NDC 33342-276-07 Bottle of 90 .......................................
NDC 33342-276-10 Carton of 100 tablets (10 x 10 unit-dose)….. NDC 33342-276-12 Darifenacin extended-release tablets, 15 mg are light peach-colored, round, bi-convex, film coated and are debossed with “L49” on one side and plain on the other side. Bottle of 30 ................................
NDC 33342-277-07 Bottle of 90 ................................ NDC 33342-277-10 Carton of 100 tablets (10 x 10 unit-dose)… NDC 33342-277-12 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light.
Keep this and all drugs out of the reach of children.
📋 Description ▾
11 DESCRIPTION Darifenacin is an extended-release tablet for oral administration which contains 7.5 mg or 15 mg darifenacin as its hydrobromide salt. The active moiety, darifenacin, is a potent muscarinic receptor antagonist. Chemically, darifenacin hydrobromide is (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetamide hydrobromide.
The empirical formula of darifenacin hydrobromide is C 28 H 30 N 2 O 2 •HBr. The structural formula is: Darifenacin hydrobromide is a white to almost white, crystalline powder, with a molecular weight of 507.5. Darifenacin is a once-a-day extended-release tablet and contains the following inactive ingredients: dibasic calcium phosphate anhydrous, hypromellose, colloidal silicon dioxide, magnesium stearate, polyethylene glycol, talc, titanium dioxide.
The 15 mg tablet also contains ferric oxide red and ferric oxide yellow. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information). Patients should be informed that anticholinergic agents, such as darifenacin, may produce clinically significant adverse effects related to anticholinergic pharmacological activity including constipation, urinary retention and blurred vision. Heat prostration (due to decreased sweating) can occur when anticholinergics such as darifenacin are used in a hot environment.
Because anticholinergics, such as darifenacin, may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug’s effects have been determined. Patients should read the patient information leaflet before starting therapy with darifenacin. Patients should be informed that darifenacin may produce clinically significant angioedema that may result in airway obstruction.
Patients should be advised to promptly discontinue darifenacin therapy and seek immediate medical attention if they experience edema of the tongue or laryngopharynx, or difficulty breathing. Darifenacin extended-release tablets should be taken once daily with water. They may be taken with or without food, and should be swallowed whole and not chewed, divided or crushed.
Manufactured for : Macleods Pharma USA, Inc. Princeton, NJ 08540 Manufactured by: Macleods Pharmaceuticals Ltd. Baddi, Himachal Pradesh, INDIA The brands listed are the trademarks of their respective owners and are not trademarks of Macleods’.
Revised: November 2022