Names and pronunciation
(do-lox′e-teen) Cymbalta, Drizalma, Irenka
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Drug reference
(do-lox′e-teen) Cymbalta, Drizalma, Irenka
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Func. class.: Antidepressant
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Chem. class.: Serotonin-norepineph- D rine reuptake inhibitor (SNRI)
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Do not confuse: Cymbalta/Symbyax duloxetine/fluoxetine/paroxetine/ Dexilant
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ACTION: May potentiate serotonergic, noradrenergic activity in the CNS; in studies, DULoxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake
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USES: Major depressive disorder (MDD), neuropathic pain associated with diabetic neuropathy, generalized anxiety disorder, fibromyalgia, chronic low back pain, osteoarthritis pain
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CONTRAINDICATIONS: Alcohol intoxication, alcoholism, closed-angle glaucoma, hepatic disease, hepatitis, jaundice, hypersensitivity Precautions: Pregnancy, breastfeeding, geriatric patients, mania, hypertension, renal/cardiac disease, seizures, increased intraocular pressure, anorexia nervosa, bleeding, dehydration, diabetes, hyponatremia, hypotension, hypovole- mia, orthostatic hypotension, abrupt product withdrawal
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Black Box Warning: Children, suicidal ideation Black Box Warning: Depression: mood, sensorium, affect, suicidal tendencies, increase in psychiatric symptoms, de- pression, panic; monitor children weekly face to face during first 4 wk or dosage change, then every other week for next 4 wk, then at 12 wk • B/P lying, standing; pulse q4hr; if sys- tolic B/P drops 20 mm Hg, hold product, notify prescriber; take VS q4hr in pa- tients with CV disease • Hypo/hyperglycemia: assess for each during treatment and before dosing • Hepatic studies: AST, ALT, bilirubin • Weight weekly; weight loss or gain; appetite may increase; peripheral edema may occur • Withdrawal symptoms: headache, nausea, vomiting, muscle pain, weak- ness; not common unless product is dis- continued abruptly • Malignant neuroleptic–like syndrome reaction • Serotonin syndrome: nausea/vom- iting, dizziness, facial flush, shivering, sweating • Sexual dysfunction: ejaculation dys- function, erectile dysfunction, decreased libido, orgasm dysfunction • Assistance with ambulation during be- ginning therapy; drowsiness, dizziness occur • Beers: use with caution in older adults; may exacerbate or cause SIADH • Pregnancy/breastfeeding: no well- controlled studies; use only if benefit outweighs fetal risk, complications in late third trimester have occurred; pregnancy should be registered with the Cymbalta Pregnancy Registry (866-814-6975); ex- creted in breast milk Black Box Warning: That clinical wors- ening and suicide risk may occur D • To wear sunscreen or large hat; pho- tosensitivity may occur • To notify prescriber if pregnancy is planned or suspected, or if breastfeed- ing • Improvement may occur in 4-8 wk or in up to 12 wk (geriatric patients)
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SIDE EFFECTS CNS: Insomnia, anxiety, dizziness, tremor, somnolence, fatigue, decreased appetite, decreased weight, agitation, diaphoresis, hallucinations, neuroleptic reaction, malignant–like syndrome aggression, seizures, headache, abnor- mal dreams, flushing, hot flashes, chills CV: Thrombophlebitis, peripheral edema, hypertension, palpitations, supraventric- ular dysrhythmia, orthostatic hypotension EENT: Abnormal vision ENDO: Hypo/hyperglycemia, SIADH GI: Constipation, diarrhea, dysphagia, nau- sea, vomiting, anorexia, dry mouth, colitis, gastritis, abdominal pain, hepatic failure GU: Abnormal ejaculation, urinary hesi- tation/retention/frequency, ejaculation delayed, erectile dysfunction, gyneco- logic bleeding INTEG: Photosensitivity, bruising, sweat- ing, Stevens-Johnson syndrome MS: Gait disturbance, muscle spasm, restless legs syndrome, myalgia SYST: Anaphylaxis, angioedema, serotonin syndrome, Stevens-Johnson syndrome
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INTERACTIONS • Do not use with linezolid or methylene blue IV • Narrow therapeutic index: CYP2D6 extensively metabolized products (fle- cainide, phenothiazines, propafenone, tri- cyclics, thioridazine) • Hyperthermia, rigidity, rapid fluc- tuations of vital signs, mental status changes, neuroleptic malignant syn- drome—MAOIs; coadministration con- traindicated within 14 days of MAOI use Increase: CNS depression—opioids, antihistamines, sedative/hypnotics Increase: serotonin syndrome, neuro- leptic malignant syndrome—SSRIs, sero- tonin-receptor agonists, tricyclics, traZODone Increase: bleeding risk—anticoagulants, antiplatelets, salicylates, NSAIDs Increase: action of DULoxetine—CYP1A2 inhibitors (fluvoxamine, quinolone anti- infectives); CYP2D6 inhibitors (FLUox- etine, quiNIDine, PARoxetine) Drug/Herb Increase: serotonin syndrome—St. John’s wort; avoid using together Increase: CNS depression—kava, valerian Drug/Lab Test Increase: ALT, bilirubin—alcohol Increase: blood glucose
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DOSAGE AND ROUTES Major depressive disorder • Adult: PO 40-60 mg/day as single dose or 2 divided doses Diabetic neuropathy • Adult: PO 60 mg/day Generalized anxiety disorder • Adult: PO 60 mg/day, may start with 30 mg/day × 1 wk, then increase to 60 mg/day; maintenance 60-120 mg/day Fibromyalgia • Adult: PO 30 mg/day × 1 wk, then 60 mg/day Musculoskeletal pain • Adult: PO 60 mg/day or 30 mg/day × 1 wk, then 60 mg/day Renal dose • Adult: PO Start with 20 mg, gradually increase; avoid use in severe renal disease Hepatic disease (mild, moderate, severe): Avoid use.
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Available forms: Capsules delayed release 20, 30, 40, 60 mg
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Administer: • Swallow capsules whole; do not break, crush, or chew; do not sprinkle on food or mix with liquid • Without regard to food • Store in tight container at room tem- perature; do not freeze
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Assess:
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Evaluate: • Therapeutic response: decreased de- pression
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To use sugarless gum, hard candy, frequent sips of water for dry mouth • To report urinary retention; about signs and symptoms of bleeding (GI bleeding, nosebleed, ecchymoses, bruising) • To use with caution when driving, performing other activities requiring alertness because of drowsiness, dizzi- ness, blurred vision • To avoid alcohol ingestion, MAOIs, other CNS depressants • To notify prescriber of nausea, vomit- ing, dizziness, facial flushing, shivering, sweating, confusion, hallucinations, in- coordination; may indicate serotonin syndrome • Not to discontinue medication quickly after long-term use; may cause nausea, headache, malaise; taper
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PHARMACOKINETICS Well absorbed; extensively metabolized (CYP2D6, CYP1A2) in the liver to an active metabolite; 70% of product recov- ered in urine, 20% in feces; 90% protein binding; elimination half-life 9.2-19.1 hr
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• Adult: PO 40-60 mg/day as single dose or 2 divided doses Diabetic neuropathy
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• Adult: PO 60 mg/day Generalized anxiety disorder
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• Adult: PO 60 mg/day, may start with 30 mg/day × 1 wk, then increase to 60 mg/day; maintenance 60-120 mg/day Fibromyalgia
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• Adult: PO 30 mg/day × 1 wk, then 60 mg/day Musculoskeletal pain
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• Adult: PO 60 mg/day or 30 mg/day × 1 wk, then 60 mg/day Renal dose
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• Adult: PO Start with 20 mg, gradually increase; avoid use in severe renal disease Hepatic disease (mild, moderate, severe): Avoid use.
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