DULoxetine (do-lox-e-teen) Cymbalta

 Indications

Major depressive disorder. Diabetic peripheral neuropathic

pain. Generalized anxiety disorder. Fibromyalgia.

Chronic musculoskeletal pain (including chronic

lower back pain and chronic pain from osteoarthritis).

Unlabeled Use: 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.

Pharmacokinetics

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;

the CYP2D6 enzyme system exhibits genetic polymorphism;

7% of population may be poor metabolizers

(PMs) and may have significantlyqduloxetine concentrations

and anqrisk of adverse effects.

Half-life: 12 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 6 hr 12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

use of MAO inhibitors or MAO-like drugs (linezolid or

methylene blue); Severe renal impairment (CCr 30

mL/min); Chronic hepatic impairment or substantial alcohol

use (qrisk 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

(qrisk of adverse reactions); History of seizure disorder;

Diabetes (may worsen glycemic control); Angleclosure

glaucoma; OB: Use during 3rd trimester may

result in neonatal serotonin syndrome requiring prolonged

hospitalization, respiratory and nutritional support;

Pedi: Mayqrisk of suicide attempt/ideation especially

during dose early treatment or dose adjustment;

risk may be greater in children or adolescents; Geri:q

risk of orthostatic hypotension and falls.

Adverse Reactions/Side Effects

CNS: NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, SUICIDAL

THOUGHTS, fatigue, drowsiness, insomnia, activation

of mania, dizziness, fainting, falls, nightmares.

EENT: blurred vision,qintraocular pressure. CV:q

BP, orthostatic hypotension. GI: HEPATOTOXICITY, PANCREATITIS,

pappetite, constipation, dry mouth, nausea,

diarrhea,qliver enzymes, gastritis, vomiting. F and E:

hyponatremia. GU: dysuria, abnormal orgasm, erectile

dysfunction,plibido, urinary retention. Derm: ERYTHEMA

MULTIFORME, STEVENS-JOHNSON SYNDROME,q

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). Concurrent

use with MAO-inhibitor-like drugs, such as

linezolid or methylene blue mayqrisk 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).qrisk of hepatotoxicity

with alcohol use disorder/alcohol abuse.

Drugs that affect serotonergic neurotransmitter systems,

including tricyclic antidepressants, SSRIs,

fentanyl, buspirone, tramadol, amphetamines,

and triptansqrisk of serotonin syndrome. Drugs

that inhibit CYP1A2, including fluvoxamine and

some fluoroquinolones,qlevels of duloxetine and

should be avoided. Drugs that inhibit CYP2D6, including

paroxetine, fluoxetine, and quinidineqlevels

of duloxetine and may increase the risk of adverse

reactions. Duloxetine also inhibits CYP2D6 and mayq

levels of drugs metabolized by CYP2D6, including tricyclic

antidepressants, phenothiazines, and class

Ic antiarrhythmics (propafenone and flecainide);

concurrent use should be undertaken with caution.q

risk of serious arrhythmias with thioridazine; avoid

concurrent use.qrisk of bleeding with aspirin,

NSAIDs, or warfarin.

Drug-Natural Products: Use with St. John’s

wortqserotonin 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 considerqto 60 mg once daily, then mayqby 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 mayqby 30 mg

once daily to maintenance dose of 60–120 mg once

daily.

PO (Children 7–17 yr): 30 mg once daily for 2 wk;

may then considerqto 60 mg once daily; recommended

maintenance dose30–60 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, thenqto 60

mg once daily.

Chronic Musculoskeletal Pain

PO (Adults): 60 mg once daily (may also be started on

30 mg once daily andqto 60 mg once daily after 1 wk.

Availability (generic available)

Capsules: 20 mg, 30 mg, 40 mg, 60 mg. Cost: 20 mg

$437.15/60, 30 mg $473.58/60, 60 mg $478.64/60.