duloxetine hydrochloride

duloxetine hydrochloride

Cymbalta

Pharmacologic class: Selective serotonin and norepinephrine reuptake inhibitor

Therapeutic class: Antidepressant

Pregnancy risk category C

FDA Boxed Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders, especially during first few months of therapy. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family and caregivers to observe patient closely and communicate with prescriber as needed.
• Drug isn't approved for use in pediatric patients.

Action

Unknown. May potentiate serotonergic and noradrenergic activity in CNS.

Availability

Capsules: 20 mg, 30 mg, 60 mg

⊘Indications and dosages

➣ Major depressive disorder

Adults: 20 to 30 mg P.O. b.i.d.

➣ Generalized anxiety disorder

Adults: For most patients, recommended starting dose is 60 mg P.O. once daily. For some patients, it may be desirable to start at 30 mg P.O. once daily for 1 week to allow patients to adjust to drug before increasing to 60 mg daily. While 120-mg daily dose was shown to be effective, no evidence shows that doses greater than 60 mg once daily confer additional benefit. If dosage is increased to more than 60 mg daily, increase in increments of 30 mg daily. Safety of doses above 120 mg daily not adequately evaluated.

➣ Neuropathic pain associated with peripheral neuropathy

Adults: 60 mg P.O. once daily

Contraindications

• Hypersensitivity to drug or its components
• MAO inhibitor use within past 14 days
• Uncontrolled angle-closure glaucoma

Precautions

Use cautiously in:
• hepatotoxicity, severe renal impairment, seizure disorder, activation of mania or hypomania, controlled angle-closure glaucoma
• heavy alcohol use
• pregnant or breastfeeding patients
• children.

Administration

• Give without regard to meals.
• Make sure patient swallows capsules whole without chewing or crushing. Don't sprinkle contents onto food or mix with liquids.
☞ Don't give within 14 days of MAO inhibitors. Don't give MAO inhibitors within 5 days of duloxetine withdrawal.

Route	Onset	Peak	Duration
P.O.	Unknown	6 hr	Unknown

Adverse reactions

CNS: fatigue, somnolence, dizziness, tremor, insomnia, anxiety, worsening of depression, increased risk of suicide or suicidal ideation (especially in child or adolescent)

EENT: blurred vision

GI: nausea, vomiting, diarrhea, constipation, dry mouth

GU: abnormal orgasm, erectile or ejaculatory dysfunction, delayed ejaculation, decreased libido

Skin: increased sweating, hot flashes

Other: decreased appetite, weight loss

Interactions

Drug-drug. Cimetidine, quinolone antibiotics: decreased duloxetine half-life

Desipramine, flecainide, phenothiazines, propafenone, tricyclic antidepressants: increased blood levels of these drugs

Fluoxetine, paroxetine, quinidine: increased duloxetine blood level

Fluvoxamine: increased duloxetine half-life

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatine kinase: increased levels

Drug-behaviors. Alcohol use: increased risk of hepatic damage

Smoking: decreased duloxetine bioavailability

Patient monitoring

☞ Monitor patient's mental status carefully. Stay alert for mood changes and signs of suicidal ideation, especially in child or adolescent
• Monitor liver function test results and creatinine level for evidence of hepatic impairment.
☞ Don't stop drug therapy abruptly. Dosage must be tapered gradually.

Patient teaching

• Tell patient he can take drug without regard to meals.
• Instruct patient to swallow capsules whole without chewing or crushing. Tell him not to sprinkle contents onto food or mix with liquids.
☞ Advise patient (and parent or significant other as appropriate) to monitor mental status carefully and to immediately report increased depression or suicidal thoughts or behavior (especially in child or adolescent).
☞ Tell patient not to stop taking drug abruptly. Dosage must be tapered gradually.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Instruct patient to avoid heavy alcohol use while taking drug because of increased risk of hepatic damage.
• Tell female patient to notify prescriber if she is pregnant or breastfeeding or plans to become pregnant or to breastfeed.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.