Wikipedia

Desvenlafaxine

Desvenlafaxine,sold under the brand namePristiqamong others, is a medication used to treatdepression.[5]It is anantidepressantof theserotonin-norepinephrine reuptake inhibitor(SNRI) class and is taken by mouth.[5]It is recommended that the need for further treatment be occasionally reassessed.[5]It may be less effective than its parent compoundvenlafaxine,[6]although some studies have found comparable efficacy.[7]

Desvenlafaxine
Skeletal formula
Ball-and-stick model of desvenlafaxine
Clinical data
Trade namesPristiq, Desfax, Ellefore, others
Other namesO-desmethylvenlafaxine, WY-45233
AHFS/DrugsMonograph
MedlinePlusa608022
License data
Pregnancy
category
  • AU:B2
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability80%
Protein bindingLow (30%)
MetabolismCYP2C19,[4]CYP3A4, (CYP2D6 is not involved)
Eliminationhalf-life11 h
Excretion45% excreted unchanged in urine
Identifiers
  • (RS)-4-[2-dimethylamino-1-(1-hydroxycyclohexyl)
    ethyl]phenol
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.149.615Edit this at Wikidata
Chemical and physical data
FormulaC16H25NO2
Molar mass263.381g·mol−1
3D model (JSmol)
  • OC2(C(c1ccc(O)cc1)CN(C)C)CCCCC2
  • InChI=1S/C16H25NO2/c1-17(2)12-15(13-6-8-14(18)9-7-13)16(19)10-4-3-5-11-16/h6-9,15,18-19H,3-5,10-12H2,1-2H3checkY
  • Key:KYYIDSXMWOZKMP-UHFFFAOYSA-NcheckY
☒NcheckY(what is this?)(verify)

Common side effects include dizziness,trouble sleeping,increased sweating, constipation, sleepiness,anxiety,and sexual problems.[5]Serious side effects may includesuicidein those under the age of 25,serotonin syndrome,bleeding,mania,andhigh blood pressure.[5]There is a high risk ofwithdrawal syndromewhich may occur if the dose is decreased or the medication is completely stopped.[5][8]It is unclear if use duringpregnancyorbreastfeedingis safe.[9]

Desvenlafaxine was approved for medical use in the United States in 2008.[5]In Europe its application for use was denied in 2009.[6]In 2022, it was the 208th most commonly prescribed medication in the United States, with more than 1million prescriptions.[10][11]

Medical uses

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Desvenlafaxine is primarily used as a treatment formajor depressive disorder.[12]Use has only been studied up to 8 weeks.[5]It may be less effective thanvenlafaxine,[6]although some studies have found comparable efficacy with a lower rate of nausea.[7]

Doses of 50 to 400 mg/day appear effective for major depressive disorder, although no additional benefit was demonstrated at doses greater than 50 mg/day, and adverse events and discontinuations were more frequent at higher doses.[13]

Desvenlafaxine improves theHAM-D17score[14]and measures of well-being such as the Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5).[15]

Adverse effects

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Frequency of adverse effects:[12][16][17]

Very common adverse effects include:

  • Nausea
  • Headache
  • Dizziness
  • Dry mouth
  • Hyperhidrosis
  • Diarrhea
  • Insomnia
  • Constipation
  • Fatigue

Common adverse effects include:

  • Tremor
  • Blurred vision
  • Mydriasis
  • Decreased appetite
  • Sexual dysfunction
  • Insomnia
  • Anxiety
  • Elevated cholesterol and triglycerides
  • Proteinuria
  • Vertigo
  • Feeling jittery
  • Asthenia
  • Nervousness
  • Hot flush
  • Irritability
  • Abnormal dreams
  • Urinary hesitation
  • Yawning
  • Rash

Uncommon adverse effects include:

Rare adverse effects include:

Common adverse effects whose intensity is unknown include:

Pharmacology

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Desvenlafaxine is a synthetic form of the isolated major active metabolite ofvenlafaxine,and is categorized as aserotonin-norepinephrine reuptake inhibitor(SNRI). When most normal metabolizers take venlafaxine, approximately 70% of the dose is metabolized into desvenlafaxine, so the effects of the two drugs are expected to be very similar.[18]It works by blocking the"reuptake" transportersfor keyneurotransmittersaffecting mood, thereby leaving more active neurotransmitters in thesynapse.The neurotransmitters affected areserotonin(5-hydroxytryptamine) andnorepinephrine(noradrenaline). It is approximately 10 times more potent at inhibitingserotoninuptake thannorepinephrineuptake.[19]

Transporter Ki[nM][19][20] IC50[nM][19]
SERT 40.2 47.3
NET 558.4 531.3

Approval status

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United States

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Pristiq 50 mg tablets (US)

Wyethannounced on 23 January 2007 that it received anapprovable letterfrom theFood and Drug Administrationfor desvenlafaxine. Final approval to sell the drug was contingent on a number of things, including:

  • A satisfactory FDA inspection of Wyeth'sGuayama, Puerto Ricofacility, where the drug is to be manufactured;
  • Severalpostmarketing surveillancecommitments, and follow-up studies on low-dose use, relapse, and use in children;
  • Clarity by Wyeth around the company's product education plan for physicians and patients;
  • Approval of desvenlafaxine's proprietary name, Pristiq.[21]

The FDA approved the drug for antidepressant use in February 2008, and was to be available in US pharmacies in May 2008.[22]

In March 2017, the generic form of the drug was made available in the US.[citation needed]

Canada

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On February 4, 2009,Health Canadaapproved use of desvenlafaxine for treatment of depression.[23][24]

European Union

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In 2009, an application to market desvenlafaxine formajor depressive disorderin the European Union was declined.[6]In 2012, Pfizer received authorization in Spain to market desvenlafaxine for the disorder.[25][26]In August 2022, following a 14-year approval process, desvenlafaxine was brought to the market for the disorder in Germany.[27]

Australia

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Desvenlafaxine is classified as a schedule 4 (prescription only) drug in Australia. It was listed on thePharmaceutical Benefits Scheme (PBS)in 2008 for the treatment of major depressive disorders.[28]

See also

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References

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  1. ^"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)".nctr-crs.fda.gov.FDA.Retrieved22 Oct2023.
  2. ^Anvisa(2023-03-31)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 2023-04-04).Archivedfrom the original on 2023-08-03.Retrieved2023-08-16.
  3. ^"Mental health".Health Canada.9 May 2018.Retrieved13 April2024.
  4. ^"Desvenlafaxine Metabolic pathways".SMPBD.RetrievedFebruary 3,2022.
  5. ^abcdefgh"Desvenlafaxine Succinate Monograph for Professionals".Drugs.American Society of Health-System Pharmacists.Retrieved18 March2019.
  6. ^abcd"Withdrawal Assessment Report for Dessvenlafaxime"(PDF).EMA.p. 3.Retrieved22 March2019.
  7. ^abColeman KA, Xavier VY, Palmer TL, Meaney JV, Radalj LM, Canny LM (September 2012). "An indirect comparison of the efficacy and safety of desvenlafaxine and venlafaxine using placebo as the common comparator".CNS Spectrums.17(3):131–141.doi:10.1017/S1092852912000648.PMID22883424.S2CID35165334.
  8. ^Miller K, King LM (10 July 2024). Begum J (ed.)."Withdrawal From Antidepressants: Symptoms, Causes, Treatments".WebMD.Retrieved2024-09-02.
  9. ^"Desvenlafaxine Pregnancy and Breastfeeding Warnings".Drugs.Retrieved19 March2019.
  10. ^"The Top 300 of 2022".ClinCalc.Archivedfrom the original on 30 August 2024.Retrieved30 August2024.
  11. ^"Desvenlafaxine Drug Usage Statistics, United States, 2013 - 2022".ClinCalc.Retrieved30 August2024.
  12. ^ab"PRODUCT INFORMATION – PRISTIQ desvenlafaxine (as succinate)"(PDF).TGA eBusiness Services.Pfizer Australia Pty Ltd. 10 December 2012.Retrieved8 November2013.
  13. ^Perry R, Cassagnol M (June 2009). "Desvenlafaxine: a new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder".Clinical Therapeutics.31(Pt 1):1374–1404.doi:10.1016/j.clinthera.2009.07.012.PMID19698900.
  14. ^Thase ME, Kornstein SG, Germain JM, Jiang Q, Guico-Pabia C, Ninan PT (March 2009). "An integrated analysis of the efficacy of desvenlafaxine compared with placebo in patients with major depressive disorder".CNS Spectrums.14(3):144–154.doi:10.1017/s1092852900020125.PMID19407711.S2CID32901068.
  15. ^Soares CN, Kornstein SG, Thase ME, Jiang Q, Guico-Pabia CJ (October 2009). "Assessing the efficacy of desvenlafaxine for improving functioning and well-being outcome measures in patients with major depressive disorder: a pooled analysis of 9 double-blind, placebo-controlled, 8-week clinical trials".The Journal of Clinical Psychiatry.70(10):1365–1371.doi:10.4088/JCP.09m05133blu.PMID19906341.
  16. ^"DESVENLAFAXINE tablet, extended release [Ranbaxy Pharmaceuticals Inc.]".DailyMed.Ranbaxy Pharmaceuticals Inc. March 2013.Retrieved9 November2013.
  17. ^"desvenlafaxine (Rx) - Pristiq, Khedezla".Medscape Reference.WebMD.Retrieved9 November2013.
  18. ^Lemke TL, Williams DA (2012).Foye's Principles of Medicinal Chemistry.Lippincott Williams & Wilkins. p. 609.ISBN978-1-60913-345-0.
  19. ^abcDeecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, et al. (August 2006). "Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor".The Journal of Pharmacology and Experimental Therapeutics.318(2):657–665.doi:10.1124/jpet.106.103382.PMID16675639.S2CID15063064.
  20. ^Roth BL,Driscol J (Dec 2012)."PDSP KiDatabase ".Psychoactive Drug Screening Program (PDSP).University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.Retrieved7 July2018.
  21. ^"Wyeth Receives Approvable Letter From FDA For Pristiq (Desvenlafaxine Succinate) For The Treatment Of Major Depressive Disorder"(Press release). 2007-01-23. Archived fromthe originalon 2007-02-21.Retrieved2007-04-04.
  22. ^"FDA Approves Pristiq"(Press release).Wyeth.2008-02-29. Archived fromthe originalon 2008-03-05.Retrieved2008-02-29.
  23. ^Health Canada Notice of Compliance - Pristiq[permanent dead link‍].February 4, 2009, retrieved on March 9, 2009.
  24. ^"Summary Basis of Decision (SBD)PrPristiq ".Health Canada. 2009-05-29. Archived fromthe originalon 2016-10-18.Retrieved2016-12-30.
  25. ^"Pristiq 100 mg Comprimidos de Liberacion Prolongada".AEMPS Medicines Online Information Center - CIMA.Retrieved2016-12-30.
  26. ^"Pristiq 50 mg Comprimidos de Liberacion Prolongada".AEMPS Medicines Online Information Center - CIMA.Retrieved2016-12-30.
  27. ^Möthrath C (August 1, 2022)."Desvenlafaxin: Grünes Licht nach 14 Jahren".Apotheke Adhoc(in German).Retrieved2022-08-12.
  28. ^"Desvenlafaxine succinate, tablet, (extended release), 50 mg and 100 mg (base), Pristiq®, November 2008".Pharmaceutical Benefits Scheme (PBS).
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