| 释义 |
duloxetine
du·lox·e·tine D5433150 (də-lŏk′sĭ-tēn′)n. A drug of the SNRI class, C18H19NOS, used in its hydrochloride form to treat depression, anxiety, fibromyalgia, and diabetic neuropathy.
[Perhaps du(al) (from its being a dual serotonin and norepinephrine reuptake inhibitor) + (flu)oxetine.]Translationsduloxetine
DULoxetine (do-lox-e-teen) duloxetine, Cymbalta (trade name) Classification Therapeutic: antidepressants
Pharmacologic: selective serotonin norepinephrine reuptake inhibitors
Pregnancy Category: C
IndicationsMajor depressive disorder.Diabetic peripheral neuropathic pain.Generalized anxiety disorder.Fibromyalgia.Chronic musculoskeletal pain (including chronic lower back pain and chronic pain from osteoarthritis).Stress urinary incontinence.ActionInhibits serotonin and norepinephrine reuptake in the CNS. Both antidepressant and pain inhibition are centrally mediated.Therapeutic effectsDecreased depressive symptomatology.Decreased neuropathic pain.Decreased symptoms of anxiety.Decreased pain.PharmacokineticsAbsorption: 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 hr | 12 hr |
Contraindications/PrecautionsContraindicated in: Hypersensitivity;Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);Uncontrolled angle-closure glaucoma;End-stage renal disease;Chronic hepatic impairment or substantial alcohol use (↑ 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); Obstetric: Use during 3rd trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory and nutritional support; Pediatric: 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 EffectsCentral nervous system- neuroleptic malignant syndrome (life-threatening)
- seizures (life-threatening)
- suicidal thoughts (life-threatening)
- fatigue (most frequent)
- drowsiness (most frequent)
- insomnia (most frequent)
- activation of mania
- dizziness
- nightmares
Ear, Eye, Nose, Throat- blurred vision
- ↑ intraocular pressure
CardiovascularGastrointestinal- hepatotoxicity (life-threatening)
- ↓ appetite (most frequent)
- constipation (most frequent)
- dry mouth (most frequent)
- nausea (most frequent)
- diarrhea
- ↑ liver enzymes
- gastritis
- vomiting
Fluid and ElectrolyteGenitourinary- dysuria (most frequent)
- abnormal orgasm
- erectile dysfunction
- ↓ libido
- urinary retention
Dermatologic- erythema multiforme (life-threatening)
- stevens-johnson syndrome (life-threatening)
- ↑ sweating (most frequent)
- pruritus
- rash
NeurologicMiscellaneous- serotonin syndrome (life-threatening)
InteractionsDrug-Drug interactionConcurrent 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).Concurrent use with MAO-inhibitor-like drugs, such as linezolid or methylene blue may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue ; if linezolid or methylene blue need to be started in a patient receiving duloxetine, immediately discontinue duloxetine and monitor for signs/symptoms of serotonin syndrome for 5 days or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume duloxetine therapy 24 hr after last dose of linezolid or methylene blue)↑ risk of hepatotoxicity with alcohol use disorder/alcohol abuse.Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, fentanyl, buspirone, 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, fluoxetine, and 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 Ic 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.Use with St. John's wort ↑ serotonin syndrome.Route/DosageOral (Adults) Major depressive disorder—40–60 mg/day (as 20 mg or 30 mg twice daily or as 60 mg once daily) as initial therapy, then 60 mg once daily as maintenance therapy; Generalized anxiety disorder—30–60 mg once daily as initial therapy (if initiated on 30 mg once daily, should titrate to 60 mg once daily after 1 wk), then 60–120 mg once daily as maintenance therapy; Neuropathic pain—60 mg once daily; Fibromyalgia—30 mg once daily for 1 wk, then ↑ to 60 mg once daily; Chronic musculoskeletal pain—60 mg once daily (may also be started on 30 mg once daily and ↑ to 60 mg once daily after 1 wk.Renal ImpairmentOral (Adults) Start with lower dose and ↑ gradually.AvailabilityCapsules: 20 mg, 30 mg, 60 mg Cost: 20 mg $437.15 / 60, 30 mg $473.58 / 60, 60 mg $478.64 / 60Nursing implicationsNursing assessment- Assess for sexual dysfunction (erectile dysfunction; decreased libido).
- Monitor BP 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, especially in early therapy or during dose changes. Risk may be increased in children, adolescents, and adults ≤24 yr. Restrict amount of drug available to patient.
- Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
- Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
- Depression: Assess mental status (orientation, mood, and behavior). Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
- Pain and Fibromyalgia: Assess intensity, quality, and location of pain periodically during therapy. May require several weeks for effects to be seen.
- Lab Test Considerations: May cause ↑ ALT, AST, bilirubin, CPK, and alkaline phosphatase.
- Monitor blood sugar and hemoglobin A1c. May cause slight ↑ in blood glucose.
Potential Nursing DiagnosesIneffective coping (Indications)
Risk for suicide (Adverse Reactions)
Chronic pain (Indications)
Implementation- Do not confuse duloxetine with fluoxetine or paroxetine. Do not confuse Cymbalta with Symbyax.
- Oral: 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; may cause dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue; 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.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Instruct patient to notify health care professional if signs of serotonin syndrome (mental status changes: agitation, hallucinations, coma; autonomic instability: tachycardia, labile BP, hyperthermia; neuromuscular aberrations: hyperreflexia, incoordination; and/or gastrointestinal symptoms: nausea, vomiting, diarrhea), liver damage (pruritus, dark urine, jaundice, right upper quadrant tenderness, unexplained "flu-like" symptoms) or rash 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 breast feeding. Encourage any patient exposed to duloxetine during pregnancy to register with the Cymbalta Pregnancy Registry at 1-866-814-6975 or www.cymbaltapregnancyregistry.com.
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 wk, but should be advised to continue therapy as directed. Therapy is usually continued for several months.
- Decrease in neuropathic pain associated with diabetic peripheral neuropathy.
- Decrease in chronic musculoskeletal pain and pain and soreness associated with fibromyalgia.
- Decrease in anxiety.
duloxetine (də-lŏk′sĭ-tēn′)n. A drug of the SNRI class, C18H19NOS, used in its hydrochloride form to treat depression, anxiety, fibromyalgia, and diabetic neuropathy. |