darifenacin hydrobromide

Action

Competitively antagonizes muscarinic receptors, reducing contractions of urinary bladder smooth muscle

Availability

Tablets (extended-release): 7.5 mg, 15 mg

Indications and dosages

➣ Overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency

Adults: Initially, 7.5 mg P.O. daily; may increase to 15 mg P.O. daily as early as 2 weeks after therapy begins

Dosage adjustment

• Moderate hepatic impairment

• Concurrent use of potent CYP3A4 inhibitors (such as clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, and ritonavir)

Contraindications

• Hypersensitivity to drug or its components

• Urinary retention, gastric retention, uncontrolled angle-closure glaucoma, or increased risk for these conditions

Precautions

Use cautiously in:

• decreased GI motility (such as severe constipation, ulcerative colitis, or myasthenia gravis), controlled angleclosure glaucoma, hepatic impairment

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Administer tablets whole with liquid (with or without food) once daily.

• Make sure patient doesn't chew, crush, or divide them.

• Know that drug isn't recommended for patients with severe hepatic impairment.

Adverse reactions

CNS: dizziness, asthenia

CV: hypertension

EENT: dry eyes, abnormal vision, dry throat, bronchitis, pharyngitis, rhinitis, sinusitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, dry mouth

GU: urinary tract infection or disorder, vaginitis

Musculoskeletal: back pain, arthralgia

Skin: dry skin, rash, pruritus

Other: abnormal taste, weight gain, accidental injury, flulike syndrome, pain, peripheral edema, heat prostration

Interactions

Drug-drug. Anticholinergics: increased frequency or severity of adverse reactions

CYP4502D6 inhibitors: increased darifenacin exposure and blood level

Drugs metabolized by CYP2D6 (such as flecainide, thioridazine, and tricyclic antidepressants): increased blood levels of these drugs

Patient monitoring

• Monitor liver function tests frequently; withdraw drug if liver function tests show severe hepatic impairment.

• Monitor urinary function periodically.

Patient teaching

• Instruct patient to take tablets whole with liquid, with or without food. Tell him not to chew, divide, or crush them.

• Inform patient that some over-the-counter products such as antihistamines may increase risk of side effects.

• Caution patient that drug may cause heat prostration; describe signs and symptoms.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.