Desvenlafaxine
 | |
| Clinical data | |
|---|---|
| Trade names | Pristiq, Desfax |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608022 |
| License data |
|
| Pregnancy category | |
| Routes of administration | Oral |
| ATC code | N06AX23 (WHO) |
| Legal status | |
| Legal status | |
| 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 Number |
93413-62-8  |
| PubChem (CID) | 125017 |
| IUPHAR/BPS | 7158 |
| DrugBank |
DB06700 |
| ChemSpider |
111300 |
| UNII |
NG99554ANW |
| KEGG |
D07793 |
| ChEBI |
CHEBI:83527  |
| ChEMBL |
CHEMBL1118 |
| ECHA InfoCard | 100.149.615 |
| Chemical and physical data | |
| Formula | C16H25NO2 |
| Molar mass | 263.38 g/mol |
| 3D model (Jmol) | Interactive image |
| |
| |
| (what is this?) (verify) | |
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] It is an example of evergreening.
Medical uses
Desvenlafaxine's primary use in medicine is 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
- Diarrhea
- 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 | Ki[nM][7] |
|---|---|
| SERT | 61.4 |
| NET | 2953 |
Approval status
United States
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 the disorder in 50 mg and 100 mg 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]
See also
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.
- 1 2 "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 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.
- ↑ "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.