Jump to content

Desvenlafaxine: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m →Australia: minor error correction
It is chiral, and a racemic mixture.
Tags: Mobile edit Mobile web edit Advanced mobile edit
Line 54: Line 54:


<!--Chemical data-->
<!--Chemical data-->
| IUPAC_name = 4-[2-dimethylamino-1-(1-hydroxycyclohexyl)<br />ethyl]phenol
| IUPAC_name = (''RS'')-4-[2-dimethylamino-1-(1-hydroxycyclohexyl)<br />ethyl]phenol
| C=16 | H=25 | N=1 | O=2
| C=16 | H=25 | N=1 | O=2
| smiles = OC2(C(c1ccc(O)cc1)CN(C)C)CCCCC2
| smiles = OC2(C(c1ccc(O)cc1)CN(C)C)CCCCC2

Revision as of 07:31, 14 June 2024

Desvenlafaxine
Skeletal formula
Ball-and-stick model of desvenlafaxine
Clinical data
Trade namesPristiq, Desfax, Ellefore, others
Other namesO-desmethylvenlafaxine, WY-45233
AHFS/Drugs.comMonograph
MedlinePlusa608022
License data
Pregnancy
category
  • AU: B2
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80%
Protein bindingLow (30%)
MetabolismCYP2C19,[4] CYP3A4, (CYP2D6 is not involved)
Elimination half-life11 h
Excretion45% excreted unchanged in urine
Identifiers
  • (RS)-4-[2-dimethylamino-1-(1-hydroxycyclohexyl)
    ethyl]phenol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.149.615 Edit this at Wikidata
Chemical and physical data
FormulaC16H25NO2
Molar mass263.381 g·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,3-5,10-12H2,1-2H3 checkY
  • Key:KYYIDSXMWOZKMP-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Desvenlafaxine, sold under the brand name Pristiq among others, is a medication used to treat depression.[5] It is an antidepressant of the serotonin-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 compound venlafaxine,[6] although some studies have found comparable efficacy.[7]

Common side effects include dizziness, trouble sleeping, increased sweating, constipation, sleepiness, anxiety, and sexual problems.[5] Serious side effects may include suicide in those under the age of 25, serotonin syndrome, bleeding, mania, and high blood pressure.[5] A withdrawal syndrome may occur if the dose is decreased or the medication is completely stopped.[5] It is unclear if use during pregnancy or breastfeeding is safe.[8]

Desvenlafaxine was approved for medical use in the United States in 2008.[5] In Europe its application for use was denied in 2009,[6] but it is available in Spain and Germany.[citation needed] In 2021, it was the 178th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[9][10]

Medical uses

Desvenlafaxine is primarily used as a treatment for major depressive disorder.[11] Use has only been studied up to 8 weeks.[5] It may be less effective than venlafaxine,[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.[12]

Desvenlafaxine improves the HAM-D17 score[13] and measures of well-being such as the Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5).[14]

Adverse effects

Frequency of adverse effects:[11][15][16]

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

Desvenlafaxine is a synthetic form of the isolated major active metabolite of venlafaxine, and is categorized as a serotonin-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.[17] It works by blocking the "reuptake" transporters for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin (5-hydroxytryptamine) and norepinephrine (noradrenaline). It is approximately 10 times more potent at inhibiting serotonin uptake than norepinephrine uptake.[18]

Transporter Ki[nM][18][19] IC50 [nM][18]
SERT 40.2 47.3
NET 558.4 531.3

Approval status

United States

Pristiq 50 mg tablets (US)

Wyeth announced on 23 January 2007 that it received an approvable letter from the Food and Drug Administration for desvenlafaxine. Final approval to sell the drug was contingent on a number of things, including:

  • A satisfactory FDA inspection of Wyeth's Guayama, Puerto Rico facility, where the drug is to be manufactured;
  • Several postmarketing surveillance commitments, 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.[20]

The FDA approved the drug for antidepressant use in February 2008, and was to be available in US pharmacies in May 2008.[21]

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

Canada

On February 4, 2009, Health Canada approved use of desvenlafaxine for treatment of depression.[22][23]

European Union

In 2009, an application to market desvenlafaxine for major depressive disorder in the European Union was declined.[6] In 2012, Pfizer received authorization in Spain to market desvenlafaxine for the disorder.[24][25] In August 2022, following a 14-year approval process, desvenlafaxine was brought to the market for the disorder in Germany.[26]

Australia

Desvenlafaxine is classified as a schedule 4 (prescription only) drug in Australia. It was listed on the Pharmaceutical Benefits Scheme (PBS) in 2008 for the treatment of major depressive disorders.[27]

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  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). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^ "Mental health". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  4. ^ "Desvenlafaxine Metabolic pathways". SMPBD. Retrieved February 3, 2022.
  5. ^ a b c d e f g h "Desvenlafaxine Succinate Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 18 March 2019.
  6. ^ a b c d "Withdrawal Assessment Report for Dessvenlafaxime" (PDF). EMA. p. 3. Retrieved 22 March 2019.
  7. ^ a b Coleman 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. PMID 22883424. S2CID 35165334.
  8. ^ "Desvenlafaxine Pregnancy and Breastfeeding Warnings". Drugs.com. Retrieved 19 March 2019.
  9. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  10. ^ "Desvenlafaxine - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  11. ^ a b "PRODUCT INFORMATION – PRISTIQ desvenlafaxine (as succinate)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 10 December 2012. Retrieved 8 November 2013.
  12. ^ 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. PMID 19698900.
  13. ^ 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. PMID 19407711. S2CID 32901068.
  14. ^ 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. PMID 19906341.
  15. ^ "DESVENLAFAXINE tablet, extended release [Ranbaxy Pharmaceuticals Inc.]". DailyMed. Ranbaxy Pharmaceuticals Inc. March 2013. Retrieved 9 November 2013.
  16. ^ "desvenlafaxine (Rx) - Pristiq, Khedezla". Medscape Reference. WebMD. Retrieved 9 November 2013.
  17. ^ Lemke TL, Williams DA (2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 609. ISBN 978-1-60913-345-0.
  18. ^ a b c Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH (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. PMID 16675639. S2CID 15063064.
  19. ^ Roth BL, Driscol J (Dec 2012). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 7 July 2018.
  20. ^ "Wyeth Receives Approvable Letter From FDA For Pristiq (Desvenlafaxine Succinate) For The Treatment Of Major Depressive Disorder" (Press release). 2007-01-23. Archived from the original on 2007-02-21. Retrieved 2007-04-04.
  21. ^ "FDA Approves Pristiq" (Press release). Wyeth. 2008-02-29. Archived from the original on 2008-03-05. Retrieved 2008-02-29.
  22. ^ Health Canada Notice of Compliance - Pristiq[permanent dead link]. February 4, 2009, retrieved on March 9, 2009.
  23. ^ "Summary Basis of Decision (SBD) PrPristiq". Health Canada. 2009-05-29. Archived from the original on 2016-10-18. Retrieved 2016-12-30.
  24. ^ "Pristiq 100 mg Comprimidos de Liberacion Prolongada". AEMPS Medicines Online Information Center - CIMA. Retrieved 2016-12-30.
  25. ^ "Pristiq 50 mg Comprimidos de Liberacion Prolongada". AEMPS Medicines Online Information Center - CIMA. Retrieved 2016-12-30.
  26. ^ Möthrath C (August 1, 2022). "Desvenlafaxin: Grünes Licht nach 14 Jahren". Apotheke Adhoc (in German). Retrieved 2022-08-12.
  27. ^ "Desvenlafaxine succinate, tablet, (extended release), 50 mg and 100 mg (base), Pristiq®, November 2008". Pharmaceutical Benefits Scheme (PBS).
Retrieved from "https://en.wikipedia.org/w/index.php?title=Desvenlafaxine&oldid=1228991553"