Drug Information

Drug Interaction:

Drug Interactions- summary-

+ Darifenacin

Moderate CYP3A4 inhibitors / Dilitazem / Erythromycin /Fluconazole/Verapramil
Darifenacin levels increased, no dosing adjustments recommended

Potent CYP3A4 inhibitors/ Clarithromycin/ Itraconazole / Ketoconazole / Nefazodone/
Protease release inhibitors / Nelfinavir /Ritonavir
Darifenacin levels increased , darifenacin should not exceed   7.5mg when
co-administered with potent CYP3A4 inhibitors

Darifenacin   + Anticholinergic drugs
Additive anticholinergic adverse effects occur

Dartifenacin +CYP2D6 substrates, CYP2D6 substrates/,Flecainide,/ Thioridazine/
Tricyclic antidep,Desipramine /Imipramine
Use caution when darifenacin is used with drugs metabolised by
CYP2D6 and that have a narrow therapeutic window. The mean Cmax
and AUC of imipramine were increased   in the presence of
darifenacin 30mg once daily.

Darifenacin + Digoxin
Darifenacin 30mg daily when co-administered with digoxin 0.25mg
resulted in 16% increase in Digoxin , monitor digoxin

Indication:

U.S.FDA APPROVED DRUGS FROM 01-01-08 TO 31-12-08

Drug name Indication Date of Approval

67. Darifenacin ( as hydrobrimide) 31-01-08

7.5mg/15mg MR

For the treatment of overactive bladder with

symptoms of urge urinary incontinence urgency

and frequency

ENABLEX (darifenacin) extended-release tablets

Initial U.S. Approval: 2004

RECENT MAJOR CHANGES

Warnings and Precautions: Central Nervous System Effects (5.5) 03/2012

Treatment of overactive bladder with symptoms of urfe and urinary incontinence , urgency

and frequency

Approved by (DCI) Drug Controller GENERAL - India For Marketing

(Ref- IDMA Publication)

Name of Drug Indication Date of Approval

Darfenacin Hbr 7.5mg/15mg ER tablets 31-01-2008

For the treatment of overactive Bladder with Symptoms of urge

urinary incontinence , urgency and frequency

Adverse Reaction:

GI - Abdominal pain 2% Constipation 14 % Diarrhea 2 % Dry mouth 20%

Dyspepsia 3% Nausea 3%

GU - Urinary tract infn 5%

Opthalmic - Dry eyes 2%

Miscellaneous - Asthena 2%

Contra-Indications:

Urinary or gastric retention,
Uncontrolled narrow-angle glaucoma in patients who are at risk these conditions

Special precautions-
Controlled narrow angle glaucoma- use with caution on patients being treated with darifenacin

Decreased GI motility - administer darifenacin with caution to patients with GI obstructive
disorders because of risk of gastric retention

Risk of uinary retention- adminster darifenacin extended release tablets with caution to patients with clinically significant bladder outflow becuase of risk of urinary retention.

Hepatic function impairment- observe caution

Pregnancy-
Administer during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Lactation-
Use caution before administering to breast fedding women

Children-
Safety and efficacy of dartifenacin not established in children

Dosages/ Overdosage Etc:

Indications-

Treatment of overactive bladder with symptoms of urinary incontinence , urgency and frequency

Dosage-

Initially - 7.5mg once daily After 2 weeks increase to 15mg daily if reqd.

Patients under 18 years- not recommended

INDICATIONS AND USAGE

Enablex is a muscarinic antagonist indicated for the treatment of overactive

bladder with symptoms of urge urinary incontinence, urgency and frequency.

The recommended starting dose of Enablex 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.

The daily dose of Enablex should not exceed 7.5 mg in the following patients:

Patients with moderate hepatic impairment (Child-Pugh B)

Patients taking potent CYP3A4 inhibitors

Enablex is not recommended for use in patients with severe hepatic impairment

(Child-Pugh C).

Enablex may be taken with or without food.

The tablet should be swallowed whole with water and not chewed, divided or crushed.

DOSAGE FORMS AND STRENGTHS

Extended-release tablets 7.5 mg and 15 mg.

Patient Information:

Dartifenacin may produce significant adverse reactions such as constipatin, urinary retention, and blurred vision

Heat prostration ( caused by decreased sweating ) can occur when used in hot environment

Excercise caution while engaing in potentially dangerous activities because the drug can produce dizziness and blurred vision

To be taken only once daily with liquid. May be taken with or without food.

Pharmacology/ Pharmacokinetics:

Ref- Drug Facts And Comparisons(2010)

Pharmacology-

Darifenacin is a competitive muscrainic antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions including contractions of the urinary bladder smooth muscle and stimulation of salivary glands

Pharmacokinetics-

The mean oral bioavailibility of darifenacin in EMs at steady state is estimated to be

15% and 19% for 7.5 and 15mg tablets respy.

After oral administeration of darifenacin to healthy volunteers peak plasma concentrations

of darifenacin are reached approximately 7 hours after multiple dosing , steady state plasma concentrations are reached by the sixth day of dosing

Mean(SD) Steady state Pharmacoknetic Parameters From

Darifenacin 7.5mg tablets and 15mg Extended Release tablets

Based on Pooled Data by Predicted CYP2D6 Phenotype

Darefenacin 7.5mg Darifenacin 15mg

(N=68 EM 5 PM) (N=102EM 17 PM)

AUC 24 Cmax Cavg Tmax t 1/2 AUC 24 Cmax Cavg Tmax t 1/2

(ng*h/ (ng/mL) (ngmL) (h) (h) (ng*h/ (ng/mL) (ngmL) (h) (h) mL) mL)

EM 29.24 2.01 1.22 6.49 12.43 88.9 5.76 3.7 7.61 12.05

(15.47) (1.04) (0.64) (4.19) (5.64) (67.87) (4.24) (2.83) (5.06) 12.37)

PM 67.56 4.27 2.81 5.2 19.95 157.71 9.99 6.58 6.71 7.4

(13.13) (0.98) (0.55) (1.79) (77.08) (5.09) (3.22) (3.58)

Interaction with Food:

Take with or without food

Pregnancy and lactation:

Pregnancy

Administer during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Lactation

Use caution before administering to breast fedding women Children- Safety and efficacy of dartifenacin not established in children

Darifenacin Hydrobromide @ - Anticholinergics- (2004)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation