Desvenlafaxine

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Desvenlafaxine
Desvenlafaxine.svg
Desvenlafaxine3Dan2.gif
Systematic (IUPAC) name
4-[2-dimethylamino-1-(1-hydroxycyclohexyl)
ethyl]phenol
Clinical data
Trade names Pristiq
AHFS/Drugs.com monograph
MedlinePlus a608022
Licence data US FDA:link
Pregnancy cat. B2 (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (CA) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 80%
Protein binding Low (30%)
Metabolism CYP3A4, (CYP2D6 is not involved)
Half-life 11 h
Excretion 45% excreted unchanged in urine
Identifiers
CAS number 93413-62-8 YesY
ATC code N06AX23
PubChem CID 125017
DrugBank DB06700
ChemSpider 111300 YesY
UNII NG99554ANW YesY
KEGG D07793 YesY
ChEMBL CHEMBL1118 YesY
Chemical data
Formula C16H25NO2 
Mol. mass 263.38 g/mol
 YesY (what is this?)  (verify)

Desvenlafaxine (brand name: Pristiq), also known as O-desmethylvenlafaxine, is an antidepressant of the serotonin-norepinephrine reuptake inhibitor 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 in the treatment of major depressive disorder.[2]

Adverse effects[edit]

Adverse effect incidence[2][3][4]

Very common (>10% incidence) adverse effects include:

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

Common (1-10% incidence) 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 (0.1-1% incidence) adverse effects include:

Rare (<0.1% incidence) adverse effects include:

Unknown frequency 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.[5] 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.[6]

Transporter Ki[nM][7]
SERT 61.4
NET 2953

Approval status[edit]

United States[edit]

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.[8]

The FDA approved the drug for antidepressant use in February 2008, and was to be available in US pharmacies in May 2008.[9]

Canada[edit]

On February 4, 2009, Health Canada approved use of desvenlafaxine for treatment of depression in Canada.[10] Pristiq is now available in Canadian pharmacies.

European Union[edit]

In the European Union desvenlafaxine succinate has not been approved for any indication. In 2008, Wyeth withdrew its application for Ellefore, the product under review for treatment of major depressive disorder.

Complete reporting from the European Medicines Agency regarding the withdrawal of Wyeth's application for Pristiqs, including the Withdrawal Assessment Report as well as multiple language versions of the Q and A document, is also freely available for public review.[11]

Clinical efficacy[edit]

Pristiq 50 mg tablets (US)

In clinical trials, desvenlafaxine demonstrated a significant superiority to placebo both in changes from baseline in the HAM-D17 score[12] and in measures of well being such as the Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5).[13]

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. ^ "DESVENLAFAXINE tablet, extended release [Ranbaxy Pharmaceuticals Inc.]". DailyMed. Ranbaxy Pharmaceuticals Inc. March 2013. Retrieved 9 November 2013. 
  4. ^ "desvenlafaxine (Rx) - Pristiq, Khedezla". Medscape Reference. WebMD. Retrieved 9 November 2013. 
  5. ^ Lemke, Thomas L.; Williams, David A. (2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 609. ISBN 978-1-60913-345-0. 
  6. ^ 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. 
  7. ^ Roth, BL; Driscol, J (12 January 2011). "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 9 November 2013. 
  8. ^ "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. 
  9. ^ "FDA Approves Pristiq" (Press release). Wyeth. 2008-02-29. Retrieved 2008-02-29. 
  10. ^ Health Canada Notice of Compliance - Pristiq. February 4, 2009, retrieved on March 9, 2009.
  11. ^ http://www.ema.europa.eu/humandocs/Humans/EPAR/pristiqs/pristiqsW.htm
  12. ^ 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. 
  13. ^ 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]