URITOS Imidafenacin 100mcg Film-Coated Tablet 1's
RXDRUG-DR-XY43548-1pc
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
The following symptoms associated with overactive bladder: Urinary urgency, urinary frequency, and urge urinary incontinence.
Dosage/Direction for Use
The usual adult dose for oral use is 1 tablet (100 mcg of imidafenacin) twice daily, after breakfast and evening meal. If the efficacy is insufficient, the dose may be increased up to 2 tablets (200 mcg) twice daily. Or as prescribed by the physician.
Increase in dosage should be considered when 1 tablet twice daily of imidafenacin provides insufficient efficacy and there are no safety problems. Efficacy and safety have not been established for the initial dose of imidafenacin at 2 tablets twice daily. For patients with moderate to severe hepatic impairment and with severe renal impairment, dosage of imidafenacin should be kept at 1 tablet twice daily.
Increase in dosage should be considered when 1 tablet twice daily of imidafenacin provides insufficient efficacy and there are no safety problems. Efficacy and safety have not been established for the initial dose of imidafenacin at 2 tablets twice daily. For patients with moderate to severe hepatic impairment and with severe renal impairment, dosage of imidafenacin should be kept at 1 tablet twice daily.
Overdosage
Symptoms: Urinary retention, mydriasis, excitement, tachycardia, etc.
Countermeasures: After gastric lavage or administration of activated carbon, the measures similar to those for overdosage of atropine should be taken. Appropriate measures should be taken according to individual symptoms, including urethral catheterization for urinary retention and administration of pilocarpine for mydriasis.
Countermeasures: After gastric lavage or administration of activated carbon, the measures similar to those for overdosage of atropine should be taken. Appropriate measures should be taken according to individual symptoms, including urethral catheterization for urinary retention and administration of pilocarpine for mydriasis.
Administration
Should be taken with food: Take after breakfast & evening meal.
Contraindications
[Imidafenacin (Uritos) is contraindicated in the following patients]: Patients with urinary retention. [Symptoms may be aggravated due to inhibition of bladder contraction during urination caused by the anticholinergic effect of this product.]
Patients with occluded pyloric region/duodenum/intestine or paralytic ileus. [Symptoms may be aggravated due to inhibition of contraction and motility of gastrointestinal smooth muscles caused by the anticholinergic effect of this product.]
Patients with decreased gastrointestinal motility. [Symptoms may be aggravated due to inhibition of contraction and motility of gastrointestinal smooth muscles caused by the anticholinergic effect of this product.]
Patients with angle closure glaucoma. [Symptoms may be aggravated due to an increase in intraocular pressure caused by the anticholinergic effect of this product.]
Patients with myasthenia gravis. [Symptoms may be aggravated due to a decrease in muscle tone caused by the anticholinergic effect of this product.]
Patients with severe heart disease. [Symptoms may be aggravated since abnormal electrocardiographic findings including extrasystoles have been reported.]
Patients with a history of hypersensitivity to any of the components of this product.
Patients with occluded pyloric region/duodenum/intestine or paralytic ileus. [Symptoms may be aggravated due to inhibition of contraction and motility of gastrointestinal smooth muscles caused by the anticholinergic effect of this product.]
Patients with decreased gastrointestinal motility. [Symptoms may be aggravated due to inhibition of contraction and motility of gastrointestinal smooth muscles caused by the anticholinergic effect of this product.]
Patients with angle closure glaucoma. [Symptoms may be aggravated due to an increase in intraocular pressure caused by the anticholinergic effect of this product.]
Patients with myasthenia gravis. [Symptoms may be aggravated due to a decrease in muscle tone caused by the anticholinergic effect of this product.]
Patients with severe heart disease. [Symptoms may be aggravated since abnormal electrocardiographic findings including extrasystoles have been reported.]
Patients with a history of hypersensitivity to any of the components of this product.
Special Precautions
Careful Administration [Imidafenacin (Uritos) should be administered with care in the following patients.]: Patients with dysuria. [Symptoms may be aggravated due to the anticholinergic effect of this product.]
Patients with arrhythmia. [Symptoms may be aggravated due to the anticholinergic effect of this product.]
Patients with hepatic dysfunction. [Adverse reactions may occur since this product are primarily metabolized in the liver. See Pharmacology: Pharmacokinetics: Plasma Concentrations: Population pharmacokinetic (PPK) analysis under Actions.]
Patients with renal dysfunction. [Renal excretion may be delayed.]
Patients with dementia or cognitive dysfunction. [Symptoms may be aggravated due to the anticholinergic effect of this product.]
Patients with Parkinsonian symptoms or cerebrovascular disorder. [Symptoms may be aggravated or psychoneurotic symptoms may occur.]
Patients with ulcerative colitis. [Toxic megacolon may occur.]
Patients with hyperthyroidism. [Sympathetic excitation including tachycardia may be aggravated due to the anticholinergic effect of this product.]
Important Precautions: In patients with lower urinary-tract obstructive disease, including benign prostatic hyperplasia, the volume of residual urine should be measured prior to treatment with this product, and special examinations should be performed if necessary. The patients should be monitored carefully throughout the treatment, with attention to increased volume of residual urine.
Since this product may induce eye accommodation disorder (including photophobia, blurred vision and eye abnormality), dizziness and sleepiness, patients should be instructed to operate potentially hazardous machinery, such as a car, with caution.
This product is not indicated for patients with dementia or cognitive dysfunction who cannot clearly recognize symptoms of overactive bladder.
When no satisfactory efficacy is observed, treatment with this product should not be continued chronically, and an alternative appropriate therapy should be considered.
Caution in Use: For drugs supplied in a press-through package (PTP), patients should be instructed to remove the drugs from the package prior to administration. [It has been reported that, if the PTP sheet is swallowed mistakenly, the sharp edge of the sheet may perforate the esophageal mucosa, resulting in serious complications such as mediastinitis.]
Other Precautions: An increase in hepatocellular adenoma was reported in 300 mg/kg groups of both males and females in the carcinogenicity study in mice for 2 years (at the oral doses of 30, 100, and 300 mg/kg), while increase in hepatocellular adenoma was not reported in the carcinogenicity study in rats for 2 years (at the oral doses of 3, 7, 15, and 30 mg/kg).
Prior to use of this product, clinical symptoms of patients should be confirmed with an appropriate interview, and diagnosis by exclusion of some other diseases with similar symptoms, including urinary tract infection, urinary calculus, and lower urinary tract neoplasm such as bladder cancer and prostate cancer, should be made by performing appropriate examinations such as urinalysis. In addition, special examinations should be considered to conduct, if necessary.
In patients complicated with lower urinary tract obstructive disease, including benign prostatic hypertrophy, treatment of the complication should be given priority.
Use in Children: Safety of this product has not been established in low birthweight babies, neonates, nursing infants, infants, or children (no clinical experience).
Use in the Elderly: Since physiological functions are generally reduced in the elderly, this product should be administered with care.
Patients with arrhythmia. [Symptoms may be aggravated due to the anticholinergic effect of this product.]
Patients with hepatic dysfunction. [Adverse reactions may occur since this product are primarily metabolized in the liver. See Pharmacology: Pharmacokinetics: Plasma Concentrations: Population pharmacokinetic (PPK) analysis under Actions.]
Patients with renal dysfunction. [Renal excretion may be delayed.]
Patients with dementia or cognitive dysfunction. [Symptoms may be aggravated due to the anticholinergic effect of this product.]
Patients with Parkinsonian symptoms or cerebrovascular disorder. [Symptoms may be aggravated or psychoneurotic symptoms may occur.]
Patients with ulcerative colitis. [Toxic megacolon may occur.]
Patients with hyperthyroidism. [Sympathetic excitation including tachycardia may be aggravated due to the anticholinergic effect of this product.]
Important Precautions: In patients with lower urinary-tract obstructive disease, including benign prostatic hyperplasia, the volume of residual urine should be measured prior to treatment with this product, and special examinations should be performed if necessary. The patients should be monitored carefully throughout the treatment, with attention to increased volume of residual urine.
Since this product may induce eye accommodation disorder (including photophobia, blurred vision and eye abnormality), dizziness and sleepiness, patients should be instructed to operate potentially hazardous machinery, such as a car, with caution.
This product is not indicated for patients with dementia or cognitive dysfunction who cannot clearly recognize symptoms of overactive bladder.
When no satisfactory efficacy is observed, treatment with this product should not be continued chronically, and an alternative appropriate therapy should be considered.
Caution in Use: For drugs supplied in a press-through package (PTP), patients should be instructed to remove the drugs from the package prior to administration. [It has been reported that, if the PTP sheet is swallowed mistakenly, the sharp edge of the sheet may perforate the esophageal mucosa, resulting in serious complications such as mediastinitis.]
Other Precautions: An increase in hepatocellular adenoma was reported in 300 mg/kg groups of both males and females in the carcinogenicity study in mice for 2 years (at the oral doses of 30, 100, and 300 mg/kg), while increase in hepatocellular adenoma was not reported in the carcinogenicity study in rats for 2 years (at the oral doses of 3, 7, 15, and 30 mg/kg).
Prior to use of this product, clinical symptoms of patients should be confirmed with an appropriate interview, and diagnosis by exclusion of some other diseases with similar symptoms, including urinary tract infection, urinary calculus, and lower urinary tract neoplasm such as bladder cancer and prostate cancer, should be made by performing appropriate examinations such as urinalysis. In addition, special examinations should be considered to conduct, if necessary.
In patients complicated with lower urinary tract obstructive disease, including benign prostatic hypertrophy, treatment of the complication should be given priority.
Use in Children: Safety of this product has not been established in low birthweight babies, neonates, nursing infants, infants, or children (no clinical experience).
Use in the Elderly: Since physiological functions are generally reduced in the elderly, this product should be administered with care.
Use In Pregnancy & Lactation
Administration of this product is not recommended to pregnant women or women suspected of being pregnant. [Safety of this product has not been established during pregnancy. Transfer to fetus was reported in animal studies (in rats).]
Administration of this product is not recommended during breast feeding. When unavoidable, nursing mothers should discontinue breast feeding during treatment of this product. [Transfer to breast milk was reported in animal studies (in rats).]
Administration of this product is not recommended during breast feeding. When unavoidable, nursing mothers should discontinue breast feeding during treatment of this product. [Transfer to breast milk was reported in animal studies (in rats).]
Adverse Reactions
Clinically significant adverse reactions: Acute glaucoma (incidence: 0.06%): Since incidence of acute glaucoma induced by increased intraocular pressure has been reported, patients should be monitored carefully. When such a symptom is observed, administration should be discontinued, and appropriate measures should be taken immediately.
Urinary retention (frequency unknown): Since urinary retention may occur, patients should be monitored carefully. When symptoms are observed, administration should be discontinued, and appropriate measures should be taken.
Hepatic dysfunction (frequency unknown): Since hepatic dysfunction with increased AST(GOT), ALT(GPT) and bilirubin may occur, patients should be monitored carefully. When these abnormalities in laboratory test values are observed, administration should be discontinued, and appropriate measures should be taken immediately.
Paralytic Ileus (frequency unknown): When symptoms including severe constipation and abdominal distention are observed, administration should be discontinued, and appropriate measures should be taken.
Hallucination/delirium (frequency unknown): When these symptoms are observed, administration should be discontinued, and appropriate measures should be taken.
QT prolongation, ventricular tachycardia (frequency unknown): It has been reported that QT prolongation, ventricular tachycardia, atrioventricular block, bradycardia, etc. occur. When these symptoms are observed, administration should be discontinued, and appropriate measures should be taken.
Other adverse reactions: See Table 8.
Urinary retention (frequency unknown): Since urinary retention may occur, patients should be monitored carefully. When symptoms are observed, administration should be discontinued, and appropriate measures should be taken.
Hepatic dysfunction (frequency unknown): Since hepatic dysfunction with increased AST(GOT), ALT(GPT) and bilirubin may occur, patients should be monitored carefully. When these abnormalities in laboratory test values are observed, administration should be discontinued, and appropriate measures should be taken immediately.
Paralytic Ileus (frequency unknown): When symptoms including severe constipation and abdominal distention are observed, administration should be discontinued, and appropriate measures should be taken.
Hallucination/delirium (frequency unknown): When these symptoms are observed, administration should be discontinued, and appropriate measures should be taken.
QT prolongation, ventricular tachycardia (frequency unknown): It has been reported that QT prolongation, ventricular tachycardia, atrioventricular block, bradycardia, etc. occur. When these symptoms are observed, administration should be discontinued, and appropriate measures should be taken.
Other adverse reactions: See Table 8.
Drug Interactions
Imidafenacin is primarily metabolized by CYP3A4 and UGT1A4 in the liver. [See Pharmacology: Pharmacokinetics: Metabolism under Actions.]
Precaution for co-administration [Imidafenacin (Uritos) should be administered with care when co-administered with the following drugs]: See Table 9.
Precaution for co-administration [Imidafenacin (Uritos) should be administered with care when co-administered with the following drugs]: See Table 9.
Storage
Store at temperatures not exceeding 30°C.
Action
Pharmacology: Pharmacodynamics: Mode of Action: Contraction of the urinary bladder is known to be induced by acetylcholine with mediation of muscarinic acetylcholine receptor subtype M3. Acetylcholine release from the nerve terminal of the urinary bladder is probably enhanced by a stimulus to muscarinic acetylcholine receptor subtype M1. Imidafenacin antagonizes subtypes M3 on the smooth muscle of the bladder and M1 in vitro. In the urinary bladder, imidafenacin inhibits acetylcholine release by antagonizing subtype M1 and contraction of smooth muscles by antagonizing subtype M3. Compared with the inhibitory effect on the salivary gland, imidafenacin shows higher inhibitory effect on the urinary bladder contraction, probably indicating efficacy and safety of this product in clinical practice.
Pharmacological Activity: Activity in the muscarinic acetylcholine receptor subtypes (in vitro): Antagonistic activity of imidafenacin was investigated on muscarinic acetylcholine receptors in vas deferens (M1), atrium (M2), and ileum (M3) using tissue specimens prepared from rabbits and guinea pigs. Imidafenacin showed higher antagonistic activity in the ileum (M3) and vas deferens (M1), compared with the atrium (M2). Major metabolites in humans showed no antagonistic activity in the muscarinic acetylcholine receptor subtypes.
Antagonistic activity of imidafenacin was investigated in recombinant human muscarinic acetylcholine receptor subtypes M1, M2, and M3 in the receptor binding assay. Imidafenacin showed high affinities for subtypes M3 and M1.
Imidafenacin inhibited acetylcholine release and urinary bladder contraction by antagonizing subtypes M3 and M1 in the tissue specimens prepared from rats.
Activity in the urinary bladder (in vivo): Imidafenacin decreased rhythmic contraction of the rat urinary bladder dose-dependently.
Imidafenacin inhibited a carbachol-induced decrease in the capacity of the rat urinary bladder dose dependently.
Selectivity for the urinary bladder: In rats, the activity ratio of inhibition of rhythmic contraction in the urinary bladder to carbachol-induced salivary secretion was about 10 times higher in imidafenacin than in propiverine hydrochloride, demonstrating high selectivity of imidafenacin for the urinary bladder.
Evaluation of rat performance in the Morris water maze task indicated that antagonistic activity of imidafenacin on subtype M1 was unlikely to impair spatial learning and memory.
Clinical Studies: Double-blind Placebo-controlled Study: Imidafenacin was orally administered at the dose of 0.1 mg twice daily for 12 weeks to patients with overactive bladder. For the primary efficacy outcome, change in total number of urinary incontinence per week from the baseline value, significant improvement was observed in the imidafenacin group compared with the placebo group. In addition, significant improvement was also observed in changes in mean frequency of urination per day and mean frequency of urinary urgency per day from the baseline values in the imidafenacin group compared with the placebo group.
Adverse reactions in the imidafenacin group including abnormalities in laboratory test values were reported in 130 (40.5%) of 321 cases evaluated. Major adverse reactions included thirst in 87 cases (27.1%) and constipation in 30 cases (9.3%). (See Table 2.)
Pharmacological Activity: Activity in the muscarinic acetylcholine receptor subtypes (in vitro): Antagonistic activity of imidafenacin was investigated on muscarinic acetylcholine receptors in vas deferens (M1), atrium (M2), and ileum (M3) using tissue specimens prepared from rabbits and guinea pigs. Imidafenacin showed higher antagonistic activity in the ileum (M3) and vas deferens (M1), compared with the atrium (M2). Major metabolites in humans showed no antagonistic activity in the muscarinic acetylcholine receptor subtypes.
Antagonistic activity of imidafenacin was investigated in recombinant human muscarinic acetylcholine receptor subtypes M1, M2, and M3 in the receptor binding assay. Imidafenacin showed high affinities for subtypes M3 and M1.
Imidafenacin inhibited acetylcholine release and urinary bladder contraction by antagonizing subtypes M3 and M1 in the tissue specimens prepared from rats.
Activity in the urinary bladder (in vivo): Imidafenacin decreased rhythmic contraction of the rat urinary bladder dose-dependently.
Imidafenacin inhibited a carbachol-induced decrease in the capacity of the rat urinary bladder dose dependently.
Selectivity for the urinary bladder: In rats, the activity ratio of inhibition of rhythmic contraction in the urinary bladder to carbachol-induced salivary secretion was about 10 times higher in imidafenacin than in propiverine hydrochloride, demonstrating high selectivity of imidafenacin for the urinary bladder.
Evaluation of rat performance in the Morris water maze task indicated that antagonistic activity of imidafenacin on subtype M1 was unlikely to impair spatial learning and memory.
Clinical Studies: Double-blind Placebo-controlled Study: Imidafenacin was orally administered at the dose of 0.1 mg twice daily for 12 weeks to patients with overactive bladder. For the primary efficacy outcome, change in total number of urinary incontinence per week from the baseline value, significant improvement was observed in the imidafenacin group compared with the placebo group. In addition, significant improvement was also observed in changes in mean frequency of urination per day and mean frequency of urinary urgency per day from the baseline values in the imidafenacin group compared with the placebo group.
Adverse reactions in the imidafenacin group including abnormalities in laboratory test values were reported in 130 (40.5%) of 321 cases evaluated. Major adverse reactions included thirst in 87 cases (27.1%) and constipation in 30 cases (9.3%). (See Table 2.)
Long-term Study: Imidafenacin was orally administered at the dose of 0.1 mg twice daily for 52 weeks to patients with overactive bladder. Improvement was observed in changes in total number of urinary incontinence per week, mean frequency of urination per day, and mean frequency of urinary urgency per day from the baseline values, with duration for 52 weeks without attenuation.
Adverse reactions in the imidafenacin group including abnormalities in laboratory test values were reported in 223 (46.7%) of 478 cases evaluated. Major adverse reactions included thirst in 164 cases (34.3 %) and constipation in 43 cases (9.0%). (See Table 3.)
Adverse reactions in the imidafenacin group including abnormalities in laboratory test values were reported in 223 (46.7%) of 478 cases evaluated. Major adverse reactions included thirst in 164 cases (34.3 %) and constipation in 43 cases (9.0%). (See Table 3.)
Long-term Ascending-dose Study: Imidafenacin was orally administered at the dose of 0.1 mg twice daily for 12 weeks to patients with overactive bladder. Then, imidafenacin was orally administered at the dose of 0.2 mg twice daily for 52 weeks in the dose increased group, and at the dose of 0.1 mg twice daily for 40 weeks in the dose maintained group according to the criteria for dose increase. In the group of 0.4 mg/day, improvement was observed in changes in total number of urinary incontinence per week, mean frequency of urination per day, and mean frequency of urinary urgency per day from the baseline values, with duration for 64 weeks after the start of the study (52 weeks after dose increase) without attenuation.
There were 49.4% (215 of 435) patients who experienced adverse drug reactions including abnormalities in laboratory test values, reported in the safety analysis set. Among them, 62.6% (114 of 182) of patients were in the dose increased group and 39.9% (101 of 253) of patients were in the dose maintained group. The most common adverse drug reactions were dry mouth and constipation, and the incident ratios were 53.3% (97 of 182) and 18.7% (34 of 182) in the dose increased group, 26.5% (67 of 253) and 9.9% (25 of 253) in the dose maintained group, respectively. (See Table 4.)
There were 49.4% (215 of 435) patients who experienced adverse drug reactions including abnormalities in laboratory test values, reported in the safety analysis set. Among them, 62.6% (114 of 182) of patients were in the dose increased group and 39.9% (101 of 253) of patients were in the dose maintained group. The most common adverse drug reactions were dry mouth and constipation, and the incident ratios were 53.3% (97 of 182) and 18.7% (34 of 182) in the dose increased group, 26.5% (67 of 253) and 9.9% (25 of 253) in the dose maintained group, respectively. (See Table 4.)
Note: Criteria for dose increase: If all symptoms of overactive bladder failed to meet the normalization criteria (mean frequency of urinary urgency per day of 0 [disappearance], mean frequency of urination per day of less than eight, and total number of episodes of urinary incontinence per week of 0 [disappearance]) at the visit after administration of the initial dose for 12 weeks, the dose of imidafenacin may be increased when the investigator judged that the dose increase should be valid, and the patient requested the dose increase. If, however, moderate to severe adverse reaction(s) had developed before the visit after 12 weeks of administration, dose increase should not be conducted.
Pharmacokinetics: Plasma Concentrations: Single administration: Effect of meal: After single oral administration of 0.1 mg of imidafenacin to healthy adult males (n=12) at the fasting state, plasma concentration reached the peak (Cmax: 471 pg/mL) at 1.5 hours, and decreased with a half-life of 2.9 hours. Cmax and AUC0-12 at the fed state were about 1.3 and 1.2 times higher than those at the fasting state, respectively. (See figure and Table 5.)
Pharmacokinetics: Plasma Concentrations: Single administration: Effect of meal: After single oral administration of 0.1 mg of imidafenacin to healthy adult males (n=12) at the fasting state, plasma concentration reached the peak (Cmax: 471 pg/mL) at 1.5 hours, and decreased with a half-life of 2.9 hours. Cmax and AUC0-12 at the fed state were about 1.3 and 1.2 times higher than those at the fasting state, respectively. (See figure and Table 5.)
Repeated administration: After repeated oral administration of 0.25 mg of imidafenacin twice daily for 5 days to the healthy adult males (n=5), the time-course of plasma concentration and pharmacokinetic parameters after the final dosing were comparable to those after the initial dosing, indicating no accumulation of imidafenacin after repeated administration.
Note: The approved dosage is 0.2 mg/day, and if the efficacy is insufficient, the dosage may be increased up to 0.4 mg/day.
The elderly: After single oral administration of 0.1 mg of imidafenacin to the healthy non-elderly adult males (n=6) and the elderly males aged 65 years or more (n=9) at the fasting state, Cmax in the elderly was about 1.2 times higher than that in the non-elderly, while AUC0-∞ was comparable between the two groups. (See Table 6.)
Note: The approved dosage is 0.2 mg/day, and if the efficacy is insufficient, the dosage may be increased up to 0.4 mg/day.
The elderly: After single oral administration of 0.1 mg of imidafenacin to the healthy non-elderly adult males (n=6) and the elderly males aged 65 years or more (n=9) at the fasting state, Cmax in the elderly was about 1.2 times higher than that in the non-elderly, while AUC0-∞ was comparable between the two groups. (See Table 6.)
Population pharmacokinetic (PPK) analysis: A two-compartment model involving primary absorption with a lag time in absorption was used for the analysis of population pharmacokinetics by NONMEM. Plasma concentration of imidafenacin was determined at a total of 3,168 points in 852 patients with overactive bladder aged 20 to 85 years (including 101 patients with mild hepatic dysfunction, 116 patients with mild renal dysfunction, and 14 patients with moderate renal dysfunction) and 90 healthy adults aged 20 to 75 years in the long-term study and long-term ascending-dose study. The relationship of clearance (CL/F) of imidafenacin to the following covariates was assessed: body weight, age, gender, drinking habit, smoking habit, indices for hepatic function (AST [GOT], ALT [GPT], γ-GTP, ALP, lactate dehydrogenase, and total bilirubin), indices for renal function (serum creatinine, and blood urea nitrogen), and albumin. CL/F in the patients with mild abnormality in ALP was lower than that in the normal patients by 4%. CL/F in the elderly was lower than that in the non-elderly by 14%. The other covariates including indices for renal function (serum creatinine, blood urea nitrogen) did not affect CL/F. (See Table 7.)
Absorption (for reference: overseas data): In the healthy adult foreign males, imidafenacin was absorbed almost 100% from the gastrointestinal tract, with an absolute bioavailability of 57.8%.
Metabolism: After oral administration, about 40% of imidafenacin was subjected to first-pass effect in the liver. Major plasma metabolites included M-2 (oxidized metabolite on the imidazole ring of imidafenacin), M-4 (ring-cleaved metabolite of M-2), and M-9 (N-glucuronide of imidafenacin). Metabolism to M-2 and M-4 was primarily catalyzed by CYP3A4, and that to M-9 was by UGT1A4. In addition, imidafenacin and its major metabolites, M-2, M-4, and M-9, did not inhibit human CYP species in vitro (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4).
Excretion (for reference: overseas data): After single oral administration of 14C-imidafenacin to healthy adult foreign males (n=6) at a dose of 0.25 mg at the fasting state, 95% of the dose was recovered in the urine and feces until 192 hours after administration (65.6% in the urine, and 29.4% in the feces). Less than 10% of the dose was excreted unchanged in the urine, and none of the dose was excreted unchanged in the feces.
Note) The approved dosage is 0.2 mg/day, and if the efficacy is insufficient, the dosage may be increased up to 0.4 mg/day.
Protein Binding: The protein binding ratio of imidafenacin ranged from 87.1 to 88.8%. Major binding proteins were albumin and α1-acid glycoprotein.
Drug Interactions: Itraconazole: After 0.1 mg of imidafenacin was orally co-administered to healthy adult males (n=10) treated with 200 mg of itraconazole once daily for 9 days, Cmax and AUC0-∞ of imidafenacin increased to 1.3 and 1.8 times those after imidafenacin was administered alone, respectively.
(For reference) Distribution in animals (in rats): After single oral administration of imidafenacin to rats, concentration in the bladder reached maximum at 1 hour after administration, and decreased with a half-life of 1.8 hours, more slowly than in the serum. Cmax and AUC0-12 in the bladder were 10.7 and 25.4 times higher than those in the serum, respectively.
Metabolism: After oral administration, about 40% of imidafenacin was subjected to first-pass effect in the liver. Major plasma metabolites included M-2 (oxidized metabolite on the imidazole ring of imidafenacin), M-4 (ring-cleaved metabolite of M-2), and M-9 (N-glucuronide of imidafenacin). Metabolism to M-2 and M-4 was primarily catalyzed by CYP3A4, and that to M-9 was by UGT1A4. In addition, imidafenacin and its major metabolites, M-2, M-4, and M-9, did not inhibit human CYP species in vitro (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4).
Excretion (for reference: overseas data): After single oral administration of 14C-imidafenacin to healthy adult foreign males (n=6) at a dose of 0.25 mg at the fasting state, 95% of the dose was recovered in the urine and feces until 192 hours after administration (65.6% in the urine, and 29.4% in the feces). Less than 10% of the dose was excreted unchanged in the urine, and none of the dose was excreted unchanged in the feces.
Note) The approved dosage is 0.2 mg/day, and if the efficacy is insufficient, the dosage may be increased up to 0.4 mg/day.
Protein Binding: The protein binding ratio of imidafenacin ranged from 87.1 to 88.8%. Major binding proteins were albumin and α1-acid glycoprotein.
Drug Interactions: Itraconazole: After 0.1 mg of imidafenacin was orally co-administered to healthy adult males (n=10) treated with 200 mg of itraconazole once daily for 9 days, Cmax and AUC0-∞ of imidafenacin increased to 1.3 and 1.8 times those after imidafenacin was administered alone, respectively.
(For reference) Distribution in animals (in rats): After single oral administration of imidafenacin to rats, concentration in the bladder reached maximum at 1 hour after administration, and decreased with a half-life of 1.8 hours, more slowly than in the serum. Cmax and AUC0-12 in the bladder were 10.7 and 25.4 times higher than those in the serum, respectively.
MedsGo Class
Drugs for Bladder & Prostate Disorders
Features
Brand
Uritos
Full Details
Dosage Strength
100 mcg
Drug Ingredients
- Imidafenacin
Drug Packaging
Film-Coated Tablet 1's
Generic Name
Imidafenacin
Dosage Form
Film-Coated Tablet
Registration Number
DR-XY43548
Drug Classification
Prescription Drug (RX)
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