Desvenlafaxine

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Desvenlafaxine
Skeletal formula
Ball-and-stick model of desvenlafaxine
Clinical data
Trade namesPristiq, Desfax, Ellefore
AHFS/Drugs.comMonograph
MedlinePlusa608022
License data
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
Routes of
administration
Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80%
Protein bindingLow (30%)
MetabolismCYP3A4, (CYP2D6 is not involved)
Elimination half-life11 h
Excretion45% excreted unchanged in urine
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.149.615 Edit this at Wikidata
Chemical and physical data
FormulaC16H25NO2
Molar mass263.38 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

Desvenlafaxine (brand name: Pristiq, Desfax, Ellefore), also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class developed and marketed by Wyeth (now part of Pfizer). Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine (sold under the brand names Effexor and Efexor). It is being targeted as the first non-hormonal based treatment for menopause.[1]

Medical uses[edit]

Desvenlafaxine's primary use in medicine is the treatment of major depressive disorder.[2]

In clinical studies, doses of 50-400 mg/day were shown to be effective for major depressive disorder (MDD), although no additional benefit was demonstrated at doses greater than 50 mg/day, and adverse events and discontinuations were more frequent at higher doses.[3]

Adverse effects[edit]

Adverse effect incidence[2][4][5]

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 however unknown intensity of adverse effects include:

Pharmacology[edit]

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.[6] 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.[7]

Transporter Ki[nM][7][8]
SERT 40.2
NET 558.4

Approval status[edit]

United States[edit]

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.[9]

The FDA approved the drug for antidepressant use in February 2008, and was to be available in US pharmacies in May 2008.[10]

In March 2017, the generic form of the drug was made available in the US.

Canada[edit]

On February 4, 2009, Health Canada approved use of desvenlafaxine for treatment of depression.[11][12] Pristiq is now available in Canadian pharmacies.

European Union[edit]

In 2008, Wyeth withdrew its application for Ellefore, the product under review for treatment of major depressive disorder in the European Union. In 2012, Pfizer received authorization in Spain to market Pristiq for the disorder in 50 mg and 100 mg tablets.[13][14][15]

Australia[edit]

Desvenlafaxine is classified as a schedule 4 (prescription only) drug in Australia. It was listed on the PBS (Pharmaceutical Benefits Scheme) in 2008 for the treatment of MDD (Major Depressive Disorders).

Clinical efficacy[edit]

In clinical trials, desvenlafaxine demonstrated a significant superiority to placebo both in changes from baseline in the HAM-D17 score[16] and in measures of well being such as the Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5).[17]

See also[edit]

References[edit]

  1. ^ "Wyeth Receives Approvable Letter From FDA for PRISTIQ for the Treatment of Vasomotor Symptoms Associated With Menopause" (Press release). Wyeth. 2007-07-24. Retrieved 2007-07-31.
  2. ^ a b "PRODUCT INFORMATION PRISTIQ® desvenlafaxine (as succinate)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 10 December 2012. Retrieved 8 November 2013.
  3. ^ Perry, Richard; Cassagnol, Manouchkathe (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. ISSN 1879-114X. PMID 19698900.
  4. ^ "DESVENLAFAXINE tablet, extended release [Ranbaxy Pharmaceuticals Inc.]". DailyMed. Ranbaxy Pharmaceuticals Inc. March 2013. Retrieved 9 November 2013.
  5. ^ "desvenlafaxine (Rx) - Pristiq, Khedezla". Medscape Reference. WebMD. Retrieved 9 November 2013.
  6. ^ Lemke, Thomas L.; Williams, David A. (2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 609. ISBN 978-1-60913-345-0.
  7. ^ a b 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" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 318 (2): 657–665. doi:10.1124/jpet.106.103382. PMID 16675639.
  8. ^ 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.
  9. ^ "Wyeth Receives Approvable Letter From FDA For Pristiq (Desvenlafaxine Succinate) For The Treatment Of Major Depressive Disorder" (Press release). 2007-01-23. Retrieved 2007-04-04.
  10. ^ "FDA Approves Pristiq" (Press release). Wyeth. 2008-02-29. Retrieved 2008-02-29.
  11. ^ Health Canada Notice of Compliance - Pristiq. February 4, 2009, retrieved on March 9, 2009.
  12. ^ "Summary Basis of Decision (SBD) PrPristiq™". Health Canada. 2009-05-29. Retrieved 2016-12-30.
  13. ^ "Pristiq 100 mg Comprimidos de Liberacion Prolongada". AEMPS Medicines Online Information Center - CIMA. Retrieved 2016-12-30.
  14. ^ "Pristiq 50 mg Comprimidos de Liberacion Prolongada". AEMPS Medicines Online Information Center - CIMA. Retrieved 2016-12-30.
  15. ^ "Pristiq" (in Spanish). Pfizer. Retrieved 2016-12-30.
  16. ^ 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 Spectr. 14 (3): 144–54. PMID 19407711.
  17. ^ 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". J Clin Psychiatry. 70 (10): 1365–71. doi:10.4088/JCP.09m05133blu. PMID 19906341.

External links[edit]