duloxetine

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >90%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2D6 and CYP1A2 isoenzymes; the CYP2D6 isoenzyme exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ duloxetine concentrations and an ↑ risk of adverse effects.

Half-Life: 12 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	6 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);
Severe renal impairment (CCr <30 mL/min);
Hepatic impairment or substantial alcohol use (↑ risk of hepatitis).

Use Cautiously in:

History of suicide attempt or ideation;
History of mania (may activate mania/hypomania);
History of seizure disorder;
Diabetes (may worsen glycemic control);
Angle-closure glaucoma;
OB: Use during 3rd trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory and nutritional support; may risk of postpartum hemorrhage in mother when used in the month before delivery;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: May risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents. Safety and effectiveness not established in children 7 yr (generalized anxiety disorder) or 13 yr (fibromyalgia);
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion and/or hyponatremia in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or dose.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, orthostatic hypotension

Derm: ↑sweating, ERYTHEMA MULTIFORME, pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS)

EENT: ↑intraocular pressure, blurred vision

Endo: SIADH

F and E: hyponatremia

GI: ↓appetite, constipation, dry mouth, nausea, ↑liver enzymes, diarrhea, gastritis, HEPATOTOXICITY, PANCREATITIS, vomiting

GU: dysuria, ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction, urinary retention

Hemat: BLEEDING

Neuro: drowsiness, fatigue, insomnia, activation of mania, dizziness, fainting, falls, NEUROLEPTIC MALIGNANT SYNDROME, nightmares, SEIZURES, SUICIDAL THOUGHTS, 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 MAO inhibitor. Wait at least 5 days after stopping duloxetine to start MAO inhibitor).
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, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans↑ risk of serotonin syndrome
Strong CYP1A2 inhibitors, including cimetidine, ciprofloxacin, and fluvoxamine, may ↑ levels; avoid concurrent use.
CYP2D6 inhibitors, including paroxetine, fluoxetine, and quinidine↑ levels of duloxetine and may increase the risk of adverse reactions.
May ↑ levels and risk of toxicity of CYP2D6 substrates, including TCAs, 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 NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, dabigatran, apixaban, edoxaban, rivaroxaban, or warfarin.

Drug-Natural Products:

Use with St. John's wort↑ serotonin syndrome.

Route/Dosage ⬆ ⬇

Major Depressive Disorder

PO (Adults ): 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

PO (Adults ≥65 yr): 30 mg once daily for 2 wk; may then consider ↑ to 60 mg once daily, then may ↑ by 30 mg once daily to maintenance dose of 60–120 mg once daily.
PO (Adults <65 yr): 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 may ↑ by 30 mg once daily to maintenance dose of 60–120 mg once daily.
PO (Children ≥7 yr): 30 mg once daily for 2 wk; may then consider ↑ to 60 mg once daily; recommended maintenance dose = 30–60 mg once daily (not to exceed 120 mg once daily).

Diabetic Peripheral Neuropathic Pain

PO (Adults ): 60 mg once daily.

Fibromyalgia

PO (Adults ): 30 mg once daily for 1 wk, then ↑ to 60 mg once daily.
PO (Children ≥13 yr): Cymbalta only: 30 mg once daily; may ↑ to 60 mg once daily based on response and tolerability.

Chronic Musculoskeletal Pain

PO (Adults ): 30 mg once daily for 1 wk, then ↑ to 60 mg once daily.

Availability ⬆ ⬇

(Generic available)

Delayed-release capsules: 20 mg; 30 mg; 40 mg; 60 mg

Assessment ⬆ ⬇

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.
Assess sexual function before starting duloxetine. Assess for changes in sexual function during treatment, including timing of onset; patient may not report.
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 SJS. 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 or Anxiety: Assess mental status (orientation, mood, and behavior). Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
Pain or Fibromyalgia: Assess intensity, quality, and location of pain periodically during therapy. May require several wk for effects to be seen.

Lab Test Considerations:

May cause ↑ ALT, AST, bilirubin, CK, and alkaline phosphatase.
- May cause hyponatremia.
- Monitor blood sugar and A1c. May cause slight ↑ in blood glucose.

Implementation ⬆ ⬇

Do not confuse duloxetine with fluoxetine, paroxetine, or Dexilant. Do not confuse Cymbalta with Symbyax.
PO: May be administered without regard to meals. DNC: Swallow capsules 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. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
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 make position changes slowly to minimize orthostatic hypotension and falls, especially in elderly patients and those taking antihypertensive medications.
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, especially NSAIDs or aspirin.
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), bleeding (ecchymoses, hematomas, epistaxis, petechiae, hemorrhage), or rash occur.
Advise patient to avoid taking alcohol during duloxetine therapy.
Inform patient that duloxetine may cause symptoms of sexual dysfunction. In males, ejaculatory delay or failure, decreased libido, and erectile dysfunction may occur. In female patients, may result in decreased libido and delayed or absent orgasm. Advise patient to notify health care professional if symptoms occur.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Use late in 3rd trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory support, and tube feeding; may occur immediately upon delivery. Symptoms include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. Use of duloxetine in last month of pregnancy may increase risk of postpartum hemorrhage. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Encourage health care professionals to register patients by contacting the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or online at https://womensmentalhealth.org/research/pregnancyregistry/. Monitor infants exposed to duloxetine via breastfeeding for sedation, poor feeding, and poor weight gain.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇