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Cymbalta
duloxetine
Black Box Warnings .
Suicidality
incr. suicidality risk in children, adolescents, and young adults w/ major depressive or other psychiatric disorders; weigh risk vs. benefit; in short-term studies of antidepressants vs. placebo, suicidality risk not incr. in pts >24 yo, and risk decr. in pts 65 yo and older; depression and certain other psychiatric disorders themselves assoc. w/ incr. suicide risk; observe all pts for clinical worsening, suicidality, or unusual behavior changes; advise families and caregivers of need for close observation and communication w/ prescriber
Adult Dosing .
Dosage forms: DR CAP: 20 mg, 30 mg, 60 mg
major depressive disorder
- [acute tx]
- Dose: 20-30 mg PO bid or 60 mg PO qd; Max: 120 mg/day; Info: may start 30 mg PO qd x1wk if tolerability concern; doses >60 mg/day rarely more effective, may incr. ADR risk; do not open cap; taper dose gradually to D/C
- [maintenance tx]
- Dose: 60 mg PO qd; Max: 120 mg/day; Info: doses >60 mg/day rarely more effective, may incr. ADR risk; do not open cap; periodically reassess need for tx; taper dose gradually to D/C
generalized anxiety disorder
- [60 mg PO qd]
- Max: 120 mg/day; Info: start 30 mg PO qd x2wk in elderly pts; may start 30 mg PO qd x1wk if tolerability concern; may incr. dose in 30 mg increments; doses >60 mg/day rarely more effective, may incr. ADR risk; do not open cap; taper dose gradually to D/C
neuropathic pain, diabetic
- [60 mg PO qd]
- Max: 120 mg/day; Info: may start 30 mg PO qd x1wk if tolerability concern; doses >60 mg/day rarely more effective, may incr. ADR risk; do not open cap; taper dose gradually to D/C
fibromyalgia
- [60 mg PO qd]
- Start: 30 mg PO qd x1wk; Max: 60 mg/day; Info: some pts may respond to 30 mg/day; do not open cap; taper dose gradually to D/C
musculoskeletal pain, chronic
- [60 mg PO qd]
- Start: 30 mg PO qd x1wk; Max: 60 mg/day; Info: do not open cap; taper dose gradually to D/C
stress urinary incontinence (off-label)
- [40 mg PO bid]
- Start: 20 mg PO bid x1wk; Info: do not open cap; taper dose gradually to D/C
peripheral neuropathy, chemo-induced (off-label)
- [60 mg PO qd]
- Start: 30 mg PO qd x1wk; Info: do not open cap; taper dose gradually to D/C
renal dosing
- [neuropathic pain, diabetic]
- CrCl 30-89: consider decr. start dose, titrate slowly; CrCl <30: avoid use
- HD/PD: not defined
- [all other indications]
- CrCl <30: avoid use
- HD/PD: not defined
hepatic dosing
- [see below]
- chronic hepatic dz or cirrhosis: avoid use
Peds Dosing .
- Dosage forms: DR CAP: 20 mg, 30 mg, 60 mg
generalized anxiety disorder
- [7-17 yo]
- Dose: 30-60 mg PO qd; Start: 30 mg PO qd, may incr. by 30 mg/day after 2wk; Max: 120 mg/day; Info: do not open cap; taper dose gradually to D/C
fibromyalgia
- [13-17 yo]
- Dose: 30-60 mg PO qd; Start: 30 mg PO qd x1wk; Max: 60 mg/day; Info: do not open cap; taper dose gradually to D/C
renal dosing
- [see below]
- CrCl <30: avoid use
- HD/PD: not defined
hepatic dosing
- [see below]
- chronic hepatic dz or cirrhosis: avoid use
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- MAO inhibitor use w/in 14 days
- CrCl <30
- hepatic dz, chronic
- cirrhosis
- alcohol abuse
- abrupt withdrawal
- caution: CNS depressant use, concurrent
- caution: smoking habit change
- caution: pts <25 yo
- caution: elderly pts
- caution: CrCl 30-89 (diabetic neuropathic pain use)
- caution: bleeding risk
- caution: hypomania hx
- caution: mania hx
- caution: diabetes mellitus
- caution: GI motility disorder
- caution: glaucoma, angle-closure
- caution: seizure hx
- caution: volume depletion
- caution: HTN
- caution: cardiovascular dz
- caution: cerebrovascular dz
Drug Interactions .
Overview
duloxetine
SNRI
- CYP1A2 substrate
- CYP2D6 substrate
- CYP2D6 inhibitor, moderate
- antiplatelet effects
- CNS depression
- hyponatremia
- hypotensive effects
- interferes w/ radiolabeled norepinephrine analog effect
- lowers seizure threshold
- serotonergic effects
- add MAO inhibitor to Interaction Check if recent (14 days) use
Contraindicated
- eliglustat
- isocarboxazid
- linezolid
- methylene blue injection
- phenelzine
- safinamide
- selegiline transdermal
- thioridazine
- tranylcypromine
- viloxazine
Avoid/Use Alternative
- 5-HTP
- aldesleukin
- alfentanil
- almotriptan
- amifampridine
- amitriptyline
- amoxapine
- amphetamine
- bromocriptine
- buprenorphine
- bupropion
- buspirone
- butalbital
- butorphanol
- carbamazepine
- ciprofloxacin
- citalopram
- clomipramine
- cocaine
- codeine
- cyclobenzaprine
- desipramine
- desvenlafaxine
- dexmethylphenidate
- dextroamphetamine
- dextromethorphan
- dihydrocodeine
- dihydroergotamine
- doxepin
- doxepin topical
- doxorubicin
- doxylamine
- duloxetine
- edoxaban
- eletriptan
- enasidenib
- enoxaparin
- ergotamine
- escitalopram
- ethanol
- fenfluramine
- fentanyl
- fluoxetine
- fluvoxamine
- fondaparinux
- frovatriptan
- gepirone
- granisetron
- hydrocodone
- hydromorphone
- imipramine
- iobenguane I 131
- iohexol
- isoniazid
- kava
- kratom
- lasmiditan
- levomilnacipran
- levorphanol
- lisdexamfetamine
- lithium
- lofexidine
- meperidine
- metaxalone
- methadone
- methamphetamine
- methylene blue oral
- methylergonovine
- methylphenidate
- metoclopramide
- midazolam
- milnacipran
- mirtazapine
- morphine
- nalbuphine
- naratriptan
- nefazodone
- nortriptyline
- oliceridine
- ondansetron
- opium
- oxybate
- oxycodone
- oxymorphone
- ozanimod
- palonosetron
- paroxetine
- pentazocine
- pimozide
- pirfenidone
- procarbazine
- promethazine
- propafenone
- protriptyline
- rasagiline
- remifentanil
- rizatriptan
- ropeginterferon alfa-2b
- SAMe
- selegiline
- sertraline
- St. John's wort
- sufentanil
- sumatriptan
- tamsulosin
- tapentadol
- thalidomide
- tramadol
- trazodone
- trimethobenzamide
- trimipramine
- venlafaxine
- vilazodone
- vortioxetine
- yohimbe
- ziprasidone
- zolmitriptan
- zuranolone
Monitor/Modify Tx
- abrocitinib
- acalabrutinib
- acebutolol
- acetazolamide
- ado-trastuzumab emtansine
- afatinib
- alfuzosin
- aliskiren
- alprazolam
- alteplase
- amantadine
- amifostine
- amiloride
- amlodipine
- anacaulase
- anagrelide
- antithrombin
- apixaban
- apomorphine
- apraclonidine ophthalmic
- argatroban
- aripiprazole
- aripiprazole bimonthly injection
- aripiprazole lauroxil
- articaine
- asenapine
- asparaginase
- aspirin
- atenolol
- avanafil
- avapritinib
- axitinib
- azilsartan medoxomil
- baclofen intrathecal
- benazepril
- berberine
- betaxolol
- betaxolol ophthalmic
- bethanechol
- bevacizumab
- bexagliflozin
- binimetinib
- bisoprolol
- bivalirudin
- bortezomib
- brexanolone
- brexpiprazole
- brimonidine ophthalmic
- brimonidine topical
- bromelain
- bromfenac ophthalmic
- bumetanide
- bupivacaine
- bupivacaine liposomal
- cabazitaxel
- cabergoline
- cabozantinib
- calaspargase
- canagliflozin
- candesartan cilexetil
- cangrelor
- cannabis
- caplacizumab
- captopril
- carfilzomib
- cariprazine
- carteolol ophthalmic
- carvedilol
- celecoxib
- chlordiazepoxide
- chloroprocaine
- chlorothiazide
- chlorpromazine
- chlorthalidone
- cilostazol
- cisplatin
- clevidipine
- clobazam
- clofarabine
- clonazepam
- clonidine
- clopidogrel
- clorazepate
- clozapine
- coenzyme Q-10
- collagenase clostridium histolyticum
- cyclophosphamide
- dabigatran
- dalteparin
- danshen
- dapagliflozin
- daprodustat
- daridorexant
- dasatinib
- deferasirox
- defibrotide
- desflurane
- desmopressin
- deutetrabenazine
- dexmedetomidine
- dexmedetomidine injection
- diazepam
- diclofenac
- diclofenac ophthalmic
- diclofenac topical
- diflunisal
- diltiazem
- dimethyl fumarate
- dinutuximab
- diosmin
- dipyridamole
- diroximel fumarate
- doxazosin
- dronabinol
- droperidol
- empagliflozin
- enalapril
- enalaprilat
- encorafenib
- entacapone
- entrectinib
- eplerenone
- epoprostenol
- eptifibatide
- erlotinib
- ertugliflozin
- esketamine
- eslicarbazepine acetate
- esmolol
- estazolam
- eszopiclone
- ethacrynic acid
- ethanol (in some formulations)
- etodolac
- evening primrose oil
- felodipine
- fenoldopam
- fenoprofen
- fenugreek
- ferumoxytol
- flaxseed
- flecainide
- flibanserin
- fluphenazine
- flurbiprofen
- flurbiprofen ophthalmic
- fosinopril
- fruquintinib
- furosemide
- gabapentin
- gabapentin enacarbil
- garlic
- gefitinib
- gemtuzumab ozogamicin
- gilteritinib
- ginkgo
- guanfacine
- haloperidol
- heparin
- hydralazine
- hydrochlorothiazide
- hydrocortisone
- hydroxyzine
- ibrutinib
- ibuprofen
- ibuprofen lysine
- icosapent ethyl
- ifosfamide
- iloperidone
- iloprost
- iloprost inhaled
- imatinib
- indapamide
- indomethacin
- inotersen
- iopamidol
- irbesartan
- iron sucrose
- isoflurane
- isosorbide dinitrate
- isosorbide mononitrate
- isradipine
- ketamine
- ketoprofen
- ketorolac
- ketorolac ophthalmic
- krill oil
- labetalol
- lemborexant
- lenvatinib
- levobunolol ophthalmic
- levodopa
- lidocaine
- lifileucel
- lisinopril
- lorazepam
- losartan
- loxapine
- lubiprostone
- lumateperone
- lurasidone
- magnesium citrate
- magnesium salicylate
- magnesium sulfate
- mannitol
- maraviroc
- meclofenamate
- mefenamic acid
- meloxicam
- mepivacaine
- methazolamide
- methohexital
- methotrexate
- methyl salicylate topical
- methyldopa
- metolazone
- metoprolol
- milrinone
- minoxidil
- mitotane
- moexipril
- molindone
- monomethyl fumarate
- nabumetone
- nadolol
- naproxen
- nattokinase
- nebivolol
- nelarabine
- nepafenac ophthalmic
- niacin (vitamin B3)
- nicardipine
- nifedipine
- nilotinib
- nimodipine
- nintedanib
- nisoldipine
- nitric oxide
- nitrite
- nitroglycerin
- nitroprusside
- nusinersen
- olanzapine
- olmesartan medoxomil
- omega-3-acid
- opicapone
- oxaprozin
- oxazepam
- oxcarbazepine
- oxybutynin
- oxytocin
- pacritinib
- paliperidone
- pazopanib
- pegaspargase
- penicillin G
- pentamidine
- pentobarbital
- pentosan polysulfate sodium
- pentoxifylline
- perindopril
- perphenazine
- phenobarbital
- phenoxybenzamine
- phentolamine
- pindolol
- piperacillin
- piroxicam
- pirtobrutinib
- pitolisant
- plasminogen, human
- polyethylene glycol
- polyethylene glycol/electrolytes
- ponatinib
- porfimer
- pralsetinib
- pramipexole
- prasugrel
- prazosin
- pregabalin
- primidone
- prochlorperazine
- propofol
- propranolol
- quazepam
- quetiapine
- quinapril
- ramipril
- ramucirumab
- ranibizumab
- regorafenib
- remimazolam
- reteplase
- riociguat
- risperidone
- rivaroxaban
- romidepsin
- ropinirole
- ropivacaine
- rotigotine transdermal
- sacubitril
- salsalate
- saw palmetto
- selinexor
- selpercatinib
- selumetinib
- sevoflurane
- sildenafil
- silodosin
- sirolimus albumin-bound
- sodium ferric gluconate complex
- sorafenib
- sotagliflozin
- sotalol
- sotatercept
- sparsentan
- spironolactone
- sulfate bowel prep
- sulindac
- sunitinib
- suvorexant
- tadalafil
- tagraxofusp
- taurine
- telmisartan
- temazepam
- tenecteplase
- terazosin
- tetrabenazine
- thiothixene
- ticagrelor
- timolol
- timolol ophthalmic
- tipranavir
- tirofiban
- tisotumab vedotin
- tivozanib
- tizanidine
- tolcapone
- tolmetin
- torsemide
- trametinib
- trandolapril
- treprostinil
- triamterene
- triazolam
- trifluoperazine
- upadacitinib
- valproic acid
- valsartan
- vandetanib
- vardenafil
- vasopressin
- verapamil
- vinpocetine
- vorapaxar
- vosoritide
- warfarin
- willow bark
- zaleplon
- zanubrutinib
- ziconotide
- ziv-aflibercept
- zolpidem
Caution Advised
- allopurinol
- baclofen
- brivaracetam
- brompheniramine
- busulfan
- caffeine
- caffeine citrate
- cannabidiol
- capmatinib
- carbinoxamine
- carisoprodol
- cenobamate
- cetirizine
- chamomile, German
- chlorambucil
- chlorpheniramine
- chlorzoxazone
- clemastine
- cyproheptadine
- dacomitinib
- dantrolene
- darifenacin
- dexchlorpheniramine
- dichlorphenamide
- difelikefalin
- difenoxin
- dimenhydrinate
- diphenhydramine
- diphenoxylate
- domperidone
- efavirenz
- estradiol (contraceptive)
- estradiol (hormone replacement)
- estrogens, conjugated (hormone replacement)
- estrogens, esterified (hormone replacement)
- ethinyl estradiol (contraceptive)
- ethinyl estradiol (hormone replacement)
- ethosuximide
- etomidate
- felbamate
- fesoterodine
- fexinidazole
- fosphenytoin
- ganaxolone
- givosiran
- glofitamab
- glycopyrrolate
- hydroxychloroquine
- hyoscyamine
- lacosamide
- lamotrigine
- leflunomide
- levetiracetam
- levocetirizine
- lindane topical
- meclizine
- melatonin
- meprobamate
- methocarbamol
- methoxsalen
- methsuximide
- metyrapone
- metyrosine
- mexiletine
- mosunetuzumab
- mycophenolate mofetil
- naltrexone
- orphenadrine
- osilodrostat
- passion flower
- perampanel
- pheniramine
- phenytoin
- pyrilamine
- quinidine (antiarrhythmic)
- quinidine (CYP2D6 inhibitor)
- ramelteon
- repotrectinib
- rifampin
- ritonavir
- rucaparib
- rufinamide
- scopolamine
- sodium phosphate (bowel prep)
- sodium picosulfate
- solifenacin
- stiripentol
- tamoxifen
- tasimelteon
- terbinafine
- teriflunomide
- tiagabine
- tolterodine
- topiramate
- trihexyphenidyl
- triprolidine
- trospium
- valbenazine
- valerian
- vemurafenib
- vigabatrin
- zonisamide
Adverse Reactions .
Serious Reactions
- suicidality
- depression exacerbation
- mania
- hypomania
- serotonin syndrome
- bleeding
- anaphylaxis
- Stevens-Johnson syndrome
- erythema multiforme
- glaucoma, angle-closure
- seizures
- hyponatremia
- SIADH
- urinary retention
- hepatotoxicity
- hepatic failure
- hypotension, orthostatic
- syncope
- extrapyramidal sx
- hypertensive crisis
- arrhythmia
- takotsubo cardiomyopathy
- withdrawal sx if abrupt D/C
Common Reactions
- nausea
- headache
- xerostomia
- weight loss
- abdominal pain
- somnolence
- fatigue
- constipation
- anorexia
- insomnia
- vomiting
- dizziness
- diarrhea
- diaphoresis
- erectile dysfxn
- agitation
- oropharyngeal pain
- libido decr.
- blurred vision
- tremor
- anxiety
- anorgasmia
- yawning
- dyspepsia
- ejaculatory dysfxn
- BP elevated
- palpitations
- urinary hesitancy
- ALT or AST elevated
- sexual dysfxn
- glucose incr.
Safety/Monitoring .
Monitoring Parameters
Cr at baseline; BP at baseline, then periodically; sx suicidality, clinical worsening, and/or unusual behavior changes, especially during initial tx or after dose changes; height, weight in children/adolescents
Look/Sound-Alike Drug Names
Cymbalta confused with: Symbyax
DULoxetine confused with: Dexilant; FLUoxetine, PARoxetine
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy, esp. in 3rd trimester; risk of fetal harm low, though risk of neonatal withdrawal sx or serotonin syndrome based on limited human data; risk of maternal postpartum hemorrhage based on human data, esp. if used w/in 1mo before delivery
Pregnancy Registry
encourage pts to enroll in National Pregnancy Registry for Antidepressants at 1-866-961-2388 or www.womensmentalhealth.org/research/pregnancyregistry/antidepressants
Lactation
Clinical Summary
may use while breastfeeding; no known risk of infant harm based on limited human data and drug properties; effects on milk production inconclusive based on conflicting human data
Pharmacology .
Metabolism: liver extensively; CYP450: 1A2, 2D6 substrate
Excretion: urine 70% (<1% unchanged), feces 20%; Half-life: 12h
Subclass: Analgesics, Centrally-acting Nonopioid ; Anxiolytics, Non-benzodiazepines ; Fibromyalgia ; Neuropathy/Neuralgia ; Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), Psychiatric
Mechanism of Action
exact mechanism of action unknown; inhibits norepinephrine and serotonin reuptake
Formulary .
No Formulary Selected
Manufacturer/Pricing .
Manufacturer: Eli Lilly and Co.
DEA/FDA: Rx
Approximate Retail Price
from http://www.goodrx.com/cymbalta
oral delayed release capsule:
- 20 mg (30 ea): $250.00
- 30 mg (30 ea): $280.00
- 60 mg (30 ea): $280.00
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