desvenlafaxine

Desvenlafaxine
Systematic (IUPAC) name
	4-[2-dimethylamino-1-(1-hydroxycyclohexyl); ethyl]phenol
Clinical data
Trade names	Pristiq, DESFAX
AHFS/Drugs.com	monograph
MedlinePlus	a608022
Licence data	US FDA:link
Pregnancy; category	AU: B2; US: C (Risk not ruled out);
Legal status	AU: Prescription Only (S4); CA: ℞-only; US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	80%
Protein binding	Low (30%)
Metabolism	CYP3A4, (CYP2D6 is not involved)
Biological half-life	11 h
Excretion	45% excreted unchanged in urine
Identifiers
CAS Registry Number	93413-62-8
ATC code	N06AX23
PubChem	CID: 125017
IUPHAR/BPS	7158
DrugBank	DB06700
ChemSpider	111300
UNII	NG99554ANW
KEGG	D07793
ChEBI	CHEBI:83527
ChEMBL	CHEMBL1118
Chemical data
Formula	C16H25NO2
Molecular mass	263.38 g/mol
	SMILES OC2(C(c1ccc(O)cc1)CN(C)C)CCCCC2 ;
	InChI 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 ; Key:KYYIDSXMWOZKMP-UHFFFAOYSA-N ;
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デスベンラファキシン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/11 23:48:15」(JST)

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Desvenlafaxine (brand name: Pristiq, DESFAX), 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

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

Adverse effects

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:

Hypersensitivity
Syncope
Depersonalisation
Hypomania
Withdrawal syndrome
Urinary retention
Epistaxis
Alopecia (hair loss)
Orthostatic hypotension
Peripheral coldness

Rare (<0.1% incidence) adverse effects include:

Hyponatraemia (low blood sodium)
Seizures
Extrapyramidal side effects
Hallucinations
Angioedema
Photosensitivity reaction
Stevens-Johnson syndrome

Unknown frequency adverse effects include:

Abnormal bleeding (e.g. gastrointestinal bleeds)
Narrow-angle glaucoma
Mania
Interstitial lung disease
Eosinophilic pneumonia
Hypertension
Suicidal behaviour & thoughts
Serotonin syndrome

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.^[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]

The molecule resembles hordenine with additions.

Transporter	K_i[nM]^[7]
SERT	61.4
NET	2953

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.^[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

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

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 such disorder under 50mg and 100mg tablets. ^[11]^[12]^[13]

Clinical efficacy

In clinical trials, desvenlafaxine demonstrated a significant superiority to placebo both in changes from baseline in the HAM-D17 score^[14] and in measures of well being such as the Sheehan Disability Scale (SDS) and 5-item World Health Organization Well-Being Index (WHO-5).^[15]

References

^ "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.
^ ^a ^b "PRODUCT INFORMATION PRISTIQ® desvenlafaxine (as succinate)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 10 December 2012. Retrieved 8 November 2013.
^ "DESVENLAFAXINE tablet, extended release [Ranbaxy Pharmaceuticals Inc.]". DailyMed. Ranbaxy Pharmaceuticals Inc. March 2013. Retrieved 9 November 2013.
^ "desvenlafaxine (Rx) - Pristiq, Khedezla". Medscape Reference. WebMD. Retrieved 9 November 2013.
^ Lemke, Thomas L.; Williams, David A. (2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. p. 609. ISBN 978-1-60913-345-0.
^ 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.
^ Roth, BL; Driscol, J (12 January 2011). "PDSP K_i 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.
^ "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.
^ "FDA Approves Pristiq" (Press release). Wyeth. 2008-02-29. Retrieved 2008-02-29.
^ Health Canada Notice of Compliance - Pristiq. February 4, 2009, retrieved on March 9, 2009.
^ http://www.aemps.gob.es/cima/especialidad.do?metodo=verPresentaciones&codigo=75561
^ http://www.aemps.gob.es/cima/especialidad.do?metodo=verPresentaciones&codigo=75560
^ https://www.pfizer.es/sobre_pfizer/medicamentos/pristiq.html
^ 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.
^ 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

Pfizer's Pristiq site for U.S. residents

UpToDate Contents

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4. 成人における単極性うつ病および初期治療：一般原則および予後 unipolar depression in adults and initial treatment general principles and prognosis
5. 更年期のほてり menopausal hot flashes

English Journal

Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine.

Liew ED, Alderman CP.SourceC/o Pharmacy Department, Repatriation General Hospital, Daw Park, SA, 5041, Australia.
International journal of clinical pharmacy.Int J Clin Pharm.2013 Nov 15. [Epub ahead of print]
Objective To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. Case summary A 57-year-old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this
PMID 24234943

Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate or severe major depressive disorder: a pooled analysis of six randomized, double-blind, placebo-controlled studies.

Papakostas GI, Culpepper L, Fayyad RS, Musgnung J, Guico-Pabia CJ.SourceaMassachusetts General Hospital, Harvard Medical School bDepartment of Family Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts cPfizer Inc., Collegeville, Pennsylvania, USA.
International clinical psychopharmacology.Int Clin Psychopharmacol.2013 Nov;28(6):312-21. doi: 10.1097/YIC.0b013e3283638fbd.
This study assessed the efficacy of desvenlafaxine 50 mg/day compared with placebo for treating moderate or severe major depressive disorder (MDD). Data were pooled from six double-blind, placebo-controlled, desvenlafaxine 50 mg/day fixed-dose studies in adults with MDD. The primary endpoint was imp
PMID 23881185

Serotonin Syndrome: Is It a Reason to Avoid the Use of Tramadol With Antidepressants?

Park SH, Wackernah RC, Stimmel GL.SourceUniversity of Southern California School of Pharmacy, Department of Clinical Pharmacy and Pharmaceutical Economics & Policy, Los Angeles, CA, USA.
Journal of pharmacy practice.J Pharm Pract.2013 Oct 23. [Epub ahead of print]
Background:There is a warning associated with all serotonergic antidepressants and its concomitant use with tramadol due to the concern for a drug-drug interaction resulting in serotonin syndrome (SS). The prescribing of antidepressants with tramadol may be unnecessarily restricted due to fear of ca
PMID 24153222

Related Pictures

[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.

[TGA-2] "PRODUCT INFORMATION PRISTIQ® desvenlafaxine (as succinate)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 10 December 2012. Retrieved 8 November 2013.

[DM-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.

[Foye2012-5] 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 K_i 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] ttp://www.aemps.gob.es/cima/especialidad.do?metodo=verPresentaciones&codigo=75561

[12] ttp://www.aemps.gob.es/cima/especialidad.do?metodo=verPresentaciones&codigo=75560

[13] ttps://www.pfizer.es/sobre_pfizer/medicamentos/pristiq.html

[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 Spectr 14 (3): 144–54. PMID 19407711.

[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". J Clin Psychiatry 70 (10): 1365–71. doi:10.4088/JCP.09m05133blu. PMID 19906341.

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