duloxetine

do-lox-e-teen

Cymbalta

Classification
Therapeutic: Pharmacologic:

Pregnancy Category C

Copyright © 2009 by F.A. Davis Company

Indications

Major depressive disorder
Diabetic peripheral neuropathic pain
Generalized anxiety disorder
Fibromyalgia
Unlabelled Uses: Stress urinary incontinence

Action

Inhibits serotonin and norepinephrine reuptake in the CNS. Both antidepressant and pain inhibition are centrally mediated
Therapeutic Effects: Decreased depressive symptomatology
Decreased neuropathic pain
Decreased symptoms of anxiety
Decreased pain

Pharmokinetics

Absorption: Well absorbed following oral administration
Distribution: Unknown
Protein Binding: Highly (> 90%) protein-bound
Metabolism and Excretion: Mostly metabolized, primarily by the CYP2D6 and CYP1A2 enzyme pathways
Half-life: 12 hr

TIME/ACTION PROFILE blood levels
ROUTE ONSET PEAK DURATION
PO unknown 6 hr12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity
Concurrent MAO inhibitor therapy
Uncontrolled angle-closure glaucoma
End stage renal disease
Chronic hepatic impairment or substantial alcohol use (increased risk of hepatitis)
Lactation: May enter breast milk; discontinue or bottle-feed
Use Cautiously in: History of suicide attempt or ideation
History of mania (may activate mania/hypomania)
Concurrent use of other centrally-acting drugs (↑ risk of adverse reactions)
History of seizure disorder
Controlled angle-closure glaucoma
Diabetic patients and those with renal impairment (consider lower initial dose with gradual increase)
OB: Use during third trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory and nutritional support
Pedi: May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents (safe use in children/adolescents not established)

Adverse Reactions/Side Effects*

*CAPITALS indicate life threatening; underlines indicate most frequent.

CNS: neuroleptic malignant syndrome, seizures, suicidal thoughts, fatigue, drowsiness, insomnia, activation of mania, dizziness, nightmares. EENT: blurred vision, ↑ intraocular pressure. CV: ↑ blood pressure. GI: hepatotoxicity, ↓ appetite, constipation, dry mouth, nausea, diarrhea, ↑ liver enzymes, gastritis, vomiting. F and E: hyponatremia. GU: dysuria, abnormal orgasm, erectile dysfunction, ↓ libido, urinary retention. Derm: ↑ sweating, pruritus, rash. Neuro: tremor. Misc: serotonin syndrome.

Interactions

Drug–Drug: Concurrent use with MAO inhibitors may result in serious potentially fatal reactions (do not use within 14 days of discontinuing MAOI. Wait at least 5 days after stopping duloxetine to start MAOI)
↑ risk of hepatotoxicity with chronic alcohol abuse
Drugs that affect serotonergic neurotransmitter systems, including linezolid, tramadol, and triptans ↑ risk of serotonin syndrome.
Drugs that inhibit CYP1A2, including fluvoxamine and some fluoroquinolones ↑ levels of duloxetine and should be avoided
Drugs that inhibit CYP2D6, including paroxetine, fluoxetineand quinidine ↑ levels of duloxetine and may increase the risk of adverse reactions
Duloxetine also inhibits CYP2D6 and may ↑ levels of drugs metabolized by CYP2D6, including tricyclic antidepressants, phenothiazines and class 1C antiarrhythmics (propafenone and flecainide); concurrent use should be undertaken with caution
↑ risk of serious arrhythmias with thioridazine; avoid concurrent use
↑ risk of bleeding with aspirin, NSAIDs, or warfarin
Drug–Natural: Use with St. John's Wort ↑of serotonin syndrome

Route/Dosage

PO (Adults): Antidepressant—20–30 mg twice daily; Neuropathic pain or generalized anxiety disorder— 60 mg once daily; Fibromyalgia-30 mg once daily for 1 wk, then ↑ to 60 mg once dailystart with lower dose and ↑ gradually

Availability

Capsules: 20 mg, 30 mg, 60 mg. Cost: 20 mg $320.96/90, 30 mg $345.99/90, 60 mg $347.98/90

NURSING IMPLICATIONS

Assessment
  • Assess for sexual dysfunction (erectile dysfunction; decreased libido)
    Monitor blood pressure before and periodically during therapy. Sustained hypertension may be dose related; decrease dose or discontinue therapy if this occurs
    Monitor appetite and nutritional intake. Weigh weekly. Report continued weight loss. Adjust diet as tolerated to support nutritional status
    Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression
    DepressionAssess mental status (orientation, mood, and behavior). Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia
    Assess suicidal tendencies in both adults and children, especially in early therapy or during dose changes. Restrict amount of drug available to patient
    Pain and FibromyalgiaAssess intensity, quality, and location of pain periodically during therapy. Use pain scale. May require several weeks for effects to be seen
  • Lab Test Considerations: May cause ↑ ALT, AST, bilirubin, CPK, and alkaline phosphatase.
Potential Nursing Diagnoses Ineffective coping (Indications)
Chronic pain (Indications)
PO: May be administered without regard to meals. Capsules should be swallowed whole. Do not crush, chew, or open and sprinkle contents on food or liquids; may affect enteric coating Patient/Family Teaching
  • Instruct patient to take duloxetine as directed at the same time each day. Take missed doses as soon as possible unless time for next dose. Do not stop abruptly; must be decreased gradually
    Encourage patient and family to be alert for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of depression and suicidal ideation, especially during early antidepressant therapy. If these symptoms occur, notify health care professional
    May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known
    Advise patient to consult health care professional prior to taking any Rx, OTC, or herbal products
    Instruct patient to notify health care professional if signs of liver damage (pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained “flu-like” symptoms) occur
    Advise patient to avoid taking alcohol during duloxetine therapy
    Instruct patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding
    Refer patient/family to local support group.
Evaluation/Desired Outcomes
  • Increased sense of well-being.
  • Renewed interest in surroundings. Need for therapy should be periodically reassessed. Patients may notice improvement within 1–4 wks, but should be advised to continue therapy as directed. Therapy is usually continued for several monthsDecrease in neuropathic pain associated with diabetic peripheral neuropathy
    Decrease in pain and soreness associated with fibromyalgia.