Darifenacin

Darifenacin Uses, Dosage, Side Effects, Food Interaction and all others data.

Darifenacin is a potent, competitive and selective muscarinic receptor antagonist which has greater binding affinity for muscarinic M3 receptors. M3 receptors are involved in the contraction of the detrusor muscle of the bladder, GI smooth muscle, saliva production, and iris sphincter function. Darifenacin may increase volume threshold in patients with involuntary detrusor contraction, thus increase bladder capacity.

Darifenacin is a competitive muscarinic receptor antagonist. In vitro studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9 and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.

Darifenacin
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Darifenacin
Availability	Prescription only
Generic	Darifenacin
Darifenacin Other Names	Darifenacin, Darifenacina, Darifénacine, Darifenacinum
Related Drugs	oxybutynin, Myrbetriq, solifenacin, tolterodine, mirabegron, Ditropan, Detrol, Botox, VESIcare, Gemtesa
Weight	15mg, 7.5mg
Type	Oral tablet, extended release
Formula	C₂₈H₃₀N₂O₂
Weight	Average: 426.55 Monoisotopic: 426.230728214
Protein binding	Darifenacin is approximately 98% bound to plasma proteins (primarily to alpha-1-acid-glycoprotein).
Groups	Approved, Investigational
Therapeutic Class	BPH/ Urinary retention/ Urinary incontinence
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Darifenacin is used for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.

Darifenacin is also used to associated treatment for these conditions: Urinary Bladder, Overactive

How Darifenacin works

Darifenacin selectively antagonizes the muscarinic M3 receptor. M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function.

Dosage

Darifenacin dosage

Darifenacin 7.5 mg once daily; may increase dose to 15 mg once daily if no adequate response after 2 wk of therapy. Darifenacin should be taken with liquid. It can be taken with or without food, and should be swallowed whole and not chewed, divided or crushed.

For patients with moderate hepatic impairment or when co-administered with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin and nefazadone), the daily dose of Darifenacin should not exceed 7.5 mg.

Side Effects

The most common side effects are dry mouth & constipation. Other less commonly reported side effects include- abnormal vision, back pain, dry skin, hypertension, vomiting, peripheral edema, weight gain, arthralgia, bronchitis, pharyngitis, rhinitis, sinusitis, rash, pruritus, urinary tract disorder and vaginitis.

Toxicity

Overdosage can potentially result in severe central anticholinergic effects.

Precaution

Darifenacin should be used with caution in the patient at risk for urinary retention & decreased gastrointestinal motility, with impaired renal & hepatic impairment.

Interaction

Darifenacin has known drug-drug interaction with CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, nelfinavir etc.). 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.

Food Interaction

Take with or without food. The absorption is unaffected by food.

[Minor] The consumption of grapefruit juice may be associated with increased plasma concentrations of darifenacin.

The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

The clinical significance is unknown.

Darifenacin Drug Interaction

Moderate: metoprolol, metoprolol, mirabegron, mirabegronMinor: acetaminophen, acetaminophenUnknown: aspirin, aspirin, multivitamin with minerals, multivitamin with minerals, warfarin, warfarin, levothyroxine, levothyroxine, vilazodone, vilazodone, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Darifenacin Disease Interaction

Major: gastric retention, glaucoma, urinary retentionModerate: CNS effects, liver disease

Volume of Distribution

163 L

Elimination Route

The mean oral bioavailability at steady state is estimated to be 15% and 19% for 7.5 mg and 15 mg tablets, respectively.

Half Life

The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.

Clearance

40 L/h [extensive metabolizers]
32 L/h [poor metabolizers]

Pregnancy & Breastfeeding use

Pregnancy Category C. Darifenacin should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus.

Lactation: 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.

Contraindication

Patient with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients who are at risk for these conditions.

Acute Overdose

Overdosage with antimuscarinic agents can result in severe antimuscarinic effects. ECG monitoring is recommended when event of overdosage is occurred. 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.