duloxetine (Cymbalta, Yentreve, Drizalma Sprinkle)
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Introduction
Tradenames: Cymbalta, Yentreve. Generic approved Dec 2103.
Indications
- depression*
- urinary stress incontinence (Yentreve)
- diabetic peripheral neuropathy[2]
- chronic musculoskeletal pain[4], including
- chemotherapy-induced painful peripheral neuropathy (first line)[6]
- generalized anxiety disorder[7]
* on list of drugs to avoid for treatment of depression[9]
- other antidepressants recommended[9]
* no significant benefit for hip osteoarthritis or knee osteoarthritis
Contraindications
- chronic liver disease or hepatic insufficiency
- co-administration of monoamine oxidase inhibitors
- uncontrolled narrow-angle glaucoma
- renal insufficiency, eGFR < 30 mL/min
Dosage
Tabs: 20,30,60 mg
Drizalma Sprinkle:
- sprinkle formulation of delayed-release duloxetine capsules
- 20, 30, 40, 60 mg
Pharmacokinetics
- median 2 hours lag before absorption begins
- maximal serum levels reached 6-10 hours after oral dosing
- food does not affect availability but delays aborption
- protein binding > 90%, to albumin & alpha-1 acid glycoprotein
- volume of distribution 1640 L
- metabolized by cyt P450 1A2 & cyt P340 2D6
- elimination 1/2life 8-17 hours
- no major differences seen in geriatric patients
- elimination 1/2life 4 hours longer in elderly women
Monitor
Adverse effects
- similar to SSRIs & venlafaxine
- nausea, xerostomia, loss of appetite, constipation[4]
- insomnia, fatigue, sexual dysfunction, dizziness, somnolence,
- mydriasis, blurred vision (frequent), diplopia (infrequent)
- hypertension, hyperhidrosis
- serious adverse effects occur in < 1% of patients
- hepatic injury (including hepatitis & cholestatic jaundice)[3][4]
- allergic reactions: hives, rash, facial edema, anigoedema?
- pneumonia[4]
- depression, suicidal ideation[4]
- may exacerbate restless legs syndrome (see venlafaxine)
- may exacerbate periodic limb movment disorder (see venlafaxine)
Drug interactions
- any drug that inhibits cyt P450 1A2 or cyt P450 2D6 may increase levels of duloxetine
- any drug that induces cyt P450 1A2 or cyt P450 2D6 may decrease levels of duloxetine
- duloxetine inhibits cyt P450 2D6 thus duloxetine may increase levels of drugs metabolized by cyt P450 2D6
- may decrease metabolism of tricyclic antidepressants, thioridazine, propafenone
- drug interaction(s) of triptans with SNRIs
- drug interaction(s) of methylene blue with SNRIs
- drug interaction(s) of linezolid with SNRIs
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
Laboratory
Mechanism of action
- inhibits reuptake of serotonin & norepinephrine about equally
- increases contractility of urethral sphincter
- centrally-acting analgesic[16]
More general terms
References
- ↑ Prescriber's Letter 11(9): 2004 Comparison of Commonly Used Antidepressants Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200901&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 2.0 2.1 Prescriber's Letter 11(9): 2004 Duloxetine (Cymbalta) for Diabetic Peripheral Neuropathy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201004&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 3.0 3.1 Medwatch http://www.fda.gov/medwatch/safety/2005/safety05.htm#Cymbalta
Prescriber's Letter 12(12): 2005 Liver function test scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=211210&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 4.0 4.1 4.2 4.3 4.4 4.5 FDA News release, Nov. 4, 2010 FDA clears Cymbalta to treat chronic musculoskeletal pain http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm232708.htm
- ↑ Prescriber's Letter 17(12): 2010 Cymbalta (Duloxetine) for Chronic Pain Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=261202&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Smith EM et al Effect of Duloxetine on Pain, Function, and Quality of Life Among Patients With Chemotherapy-Induced Painful Peripheral Neuropathy. A Randomized Clinical Trial. JAMA. 2013;309(13):1359-1367 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23549581 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1674238
- ↑ 7.0 7.1 Deprecated Reference
- ↑ FDA News Release: Dec. 11, 2013 FDA approves first generic versions of antidepressant drug Cymbalta. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm378282.htm
- ↑ 9.0 9.1 9.2 Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
- ↑ A Pocket Guide to the 2019 Beer's Criteria. American Geriatrics Society.
- ↑ http://www.Cymbalta.com
- ↑ 12.0 12.1 Drugc.com: Duloxetine https://www.drugs.com/ppa/duloxetine.html
- ↑ Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24385423 Review. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007115.pub3/full
- ↑ 14.0 14.1 Sofat N, Harrison A, Russell M, et al. The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis. J Pain Res. 2017;10:2437-2449 https://www.dovepress.com/the-effect-of-pregabalin-or-duloxetine-on-arthritis-pain-a-clinical-an-peer-reviewed-fulltext-article-JPR
- ↑ 15.0 15.1 Uchio Y, Enomoto H, Alev L, et al. A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. J Pain Res. 2018;11:809-821 https://www.dovepress.com/a-randomized-double-blind-placebo-controlled-phase-iii-trial-of-duloxe-peer-reviewed-fulltext-article-JPR
- ↑ 16.0 16.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ van den Driest JJ et al. No added value of duloxetine in patients with chronic pain due to hip or knee osteoarthritis: A cluster-randomized trial. Arthritis Rheumatol 2022 May; 74:818 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34989159 https://onlinelibrary.wiley.com/doi/10.1002/acr.24519
Lenhard NK et al. Does screening for depressive symptoms help optimize duloxetine use in knee osteoarthritis patients with moderate pain? A cost-effectiveness analysis. Arthritis Rheumatol 2022 May; 74:776 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33253496 PMCID: PMC8164641 (available on 2023-05-01) https://onlinelibrary.wiley.com/doi/10.1002/acr.24519 - ↑ Highlights of Prescribing Information Cymbalta (duloxetine) delayed release capsules for oral use https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022516lbl.pdf