Enablex (darifenacin hydrobromide)

Darifenacin hydrobromide, an antimuscarinic agent, is a genitourinary antispasmodic.

Darifenacin hydrobromide is a potent and selective antimuscarinic agent. The drug inhibits binding of acetylcholine to muscarinic receptors in cholinergically innervated organs. In vitro studies suggest that darifenacin demonstrates substantially greater binding affinity for muscarinic M3 receptors, which are involved in contraction of the detrusor muscle of the bladder and GI smooth muscle, saliva production, and iris sphincter function, than for other muscarinic receptor subtypes.

Darifenacin exhibits functional selectivity for urinary bladder over secretory (e.g., salivary) glands. In cystometric studies in patients with involuntary detrusor contractions, darifenacin increased bladder capacity and diminished frequency of unstable contractions of the detrusor muscle of the bladder.

Following oral administration in healthy individuals, peak plasma concentrations of darifenacin are achieved approximately 7 hours after multiple dosing, and steady-state plasma concentrations are achieved by the sixth day of administration. In patients with normal metabolizer phenotypes of the cytochrome P-450 (CYP) 2D6 isoenzyme (i.e., extensive metabolizers, homozygote-extensive metabolizers), the mean oral bioavailability of darifenacin at steady-state is approximately 15 or 19% for the 7.5- or 15-mg tablets, respectively; darifenacin exposure is 40 or 90% higher in heterozygote-extensive metabolizers or poor metabolizers, respectively, and 56% lower in Japanese males. Food does not affect the pharmacokinetics of darifenacin.

The drug is approximately 98% bound to plasma proteins (mainly to alpha1-acid glycoprotein). Darifenacin is extensively metabolized in the liver, mainly via CYP2D6 and CYP3A4. In a subset of individuals (approximately 7% of Caucasians and 2% of African Americans) who have poor metabolizer phenotypes of CYP2D6, darifenacin is metabolized principally via CYP3A4.

Steady-state plasma concentrations of darifenacin following administration of the 15-mg daily dosage are approximately 1.7-1.9 times higher in poor metabolizers than in extensive metabolizers of the drug. Clearance of darifenacin is approximately 40 L/hour in extensive metabolizers and 32 L/hour in poor metabolizers. Clearance of the drug appears to decrease at a rate of 6% per decade relative to a median age of 44 years; following administration of darifenacin 15 mg daily, exposure to the drug at steady-state was approximately 12-19% higher in healthy individuals 45-65 years of age than in those 18-44 years of age.

The elimination half-life of darifenacin following long-term administration is approximately 13-19 hours. Following a single oral dose of 14C-darifenacin solution in healthy individuals, approximately 60 or 40% of the dose was excreted in urine or feces, respectively; unchanged drug accounted for about 3% of the recovered radioactivity.

USES: Darifenacin is used to treat an overactive bladder. By relaxing the muscles in the bladder, darifenacin improves your ability to control your urination. It helps to reduce leaking of urine, feelings of needing to urinate right away, and frequent trips to the bathroom.

This medication belongs to the class of drugs known as antispasmodics.

Generic name: darifenacin hydrobromide
Pronunciation: (DAR-i-FEN-a-sin)

The following indications are listed for Enablex:

• Bladder Hyperactivity
• Increased Urinary Frequency
• Urinary Urge Incontinence
• Urinary Urgency

Also known as: Detrusor Overactivity, Hypertonic Bladder, Hypertonicity Of Bladder, Low Compliance Of Bladder, Overactive Detrusor, Urge Incontinence, Urge Urinary Incontinence, Urinary Frequency.

No ICD codes are available for this drug.