Fluvoxamine
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225062314
2008-07-11T18:27:34Z
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{{Drugbox|
|IUPAC_name = 2-[(5-methoxy-1- [4-(trifluoromethyl) phenyl]pentylidene) amino]oxyethanamine
| image=Fluvoxamine structure.svg
| width=180
| CAS_number=54739-18-3
| ATC_prefix=N06
| ATC_suffix=AB08
| ATC_supplemental=
| PubChem=5324346
| DrugBank=APRD00425
| C=15 | H=21 | F=3 | N=2 | O=2
| molecular_weight = 318.335
| bioavailability= 77%
| metabolism = [[Hepatic]]
| elimination_half-life= 15.6 hours
| excretion = [[Renal]]
| pregnancy_category = C
| legal_US = Rx-only
| routes_of_administration= Oral
}}
'''Fluvoxamine''' ('''Luvox''') is an [[antidepressant]] which functions as a [[selective serotonin reuptake inhibitor]]. It is most often used to treat [[obsessive-compulsive disorder]].
==History==
Fluvoxamine was one of the first of the SSRI antidepressants to be launched (1984 - Switzerland) and was developed by [[Solvay (company)|Solvay Pharmaceuticals]]. It was launched in the US in December 1994 and in Japan in June 1999. As of the end of 1995, more than 10 million patients worldwide have been treated with fluvoxamine.<ref>{{cite journal | first = | last = | date = 1999 | title = | journal = Fluvoxamine Product Monograph | volume = | issue = | pages = }}</ref> In 1999, fluvoxamine came under great public scrutiny after it was discovered that [[Eric Harris and Dylan Klebold|Eric Harris]], one of the two teenage shooters involved in the [[Columbine High School massacre]], had been taking the drug. Many immediately pointed fingers at fluvoxamine and its manufacturer Solvay Pharmaceuticals.<ref name="DenverPost">{{cite news |url=http://www.denverpost.com/golf/ci_5094436 |title=Judge: Seal Columbine papers for 25 years |accessdate=2008-03-03 |date=January 26, 2007 |format= |work=The Denver Post}}</ref> Sales fell, and Solvay withdrew the medication from the U.S. market in 2002. In 2007 Solvay re-introduced Luvox, which is now manufactured by Palo Alto, California-based Jazz Pharmaceuticals Inc.
Fluvoxamine was the first SSRI to be registered for the treatment of [[Obsessive Compulsive Disorder]] in children by FDA in 1997.<ref>{{cite journal | first = | last = | date = | title = Luvox Approved For Obsessive Compulsive Disorder in Children and Teens | journal = http://www.pslgroup.com/dg/2261a.htm | volume = | issue = | pages = }}</ref>
Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.<ref>{{cite journal | first = | last = | date = | title = Solvay’s Fluvoxamine maleate is first drug approved for the treatment of social anxiety disorder in Japan | journal = http://www.solvaypress.com/pressreleases/0,,33713-2-83,00.htm | volume = | issue = | pages = }}</ref>
On [[February 28]], [[2008]], the US FDA approved a controlled-release formulation of fluvoxamine, to be marketed as '''Luvox CR'''.<ref>{{cite web |url=http://www.jazzpharma.com/news.php?id=59 |title=Jazz Pharmaceuticals press release, February 28, 2008 - FDA APPROVES LUVOX® CR (FLUVOXAMINE MALEATE) EXTENDED-RELEASE CAPSULES FOR THE TREATMENT OF SOCIAL ANXIETY DISORDER (SAD) AND OBSESSIVE COMPULSIVE DISORDER (OCD) |accessdate=2008-03-14 |format= |work= }}</ref>
==Indications==
Fluvoxamine is widely prescribed to treat [[Clinical depression|depression]], and [[anxiety disorder]]s such as [[Obsessive-Compulsive Disorder]], [[Obsessive-Compulsive Spectrum Disorder]], [[Panic Disorder]], [[Social Phobia]], and [[Post-Traumatic Stress Disorder]].<ref>{{cite journal | first = David P. Figgit | last = Karen J. McClellan | date = Drugs Oct 2000 | title = Fluvoxamine An Updated Review of its Use in the Management of Adults with Anxiety Disorders | journal = Adis Drug Evaluation | volume = 60 | issue = 4 | pages = 925–954}}</ref>
Fluvoxamine is indicated for children and adolescents with OCD.<ref>{{cite journal | first = | last = | date = March 2005 | title = US-FDA Fluvoxamine Product Insert | journal = | volume = | issue = | pages = }}</ref>
===Unapproved/off-label/investigational===
Fluvoxamine is also used for the treatment of children and adolescents with social phobia, [[separation anxiety disorder]], or [[generalized anxiety disorder]].<ref>{{cite journal | first = Michael J. Labelarte MD et.al. | last = John T Walker MD | date = April 26, 2001 | title = Fluvoxamine for the treatment of anxiety disorders in children and adolescents | journal = The New England Journal of Medicine | volume = 344 | issue = | pages = 1279–1285 | doi = 10.1056/NEJM200104263441703 | pmid = 11323729}}</ref>
Fluvoxamine may help in the treatment of [[Irritable Bowel Syndrome]].<ref>{{cite journal | first = et al. | last = Emmanuel | date = 1997 | title = Treatment of Irritable Bowel Syndrome with Fluvoxamine | journal = Am J Psychiatry | volume = 154 | issue = | pages = 711–712}}</ref>
==Adverse effects==
[[Adverse drug reaction|Side effect]]s of fluvoxamine can include:
decreased sex drive or ability, drowsiness, tiredness, diarrhea, dizziness or light-headedness, [[constipation]], [[headache]], [[nausea]], [[nervousness]], [[sleep]] problems, increased [[sweating]], [[tremors]], serious [[skin rash]], vomiting, stomach pain, dry mouth, heart burn, loss of appetite, pins and needles, abnormal taste, increased heart beat, weight gain or loss, unusual bruising and other allergic problems such as difficulty breathing, fever, confusion, severe weakness, intense agitation or anxiety, restlessness, [[hypomania]], [[mania]], [[seizures]].
Fluvoxamine has been found to delay ejaculation in a manner similar to but less than other SSRIs including [[fluoxetine]], [[paroxetine]] and [[sertraline]]. Sexual dysfunction and anorgasmia is quite rare side effect with fluvoxamine, contrary to other SSRIs.<ref>{{cite journal | first = Waldinger MD | last = Hengeveld VW et al. | date = 1998 | title = Effect of SSRI antidepressants on ejaculation: a double blind, randomised, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline | journal = Journal of Clinical Psychopharmacology | volume = 18 | issue = | pages = 274–281 | doi = 10.1097/00004714-199808000-00004}}</ref><ref>{{cite journal| last = Riley| first = A.
| authorlink = | coauthors = R.T. Segraves| title = Treatment of Premature Ejaculation| journal = Int J. Clin Pract.| volume = 60| issue = 6| pages = 694–697| publisher = Blackwell Publishing| location = | date = 2006| url = http://www.medscape.com/viewarticle/533889_print| doi = | id = | accessdate = 2008-02-01}}</ref>
==Pharmacology==
Fluvoxamine is one of the few SSRIs to have a monocyclic structure.
Although all SSRIs inhibit the reuptake of serotonin, the pharmacological and adverse effect profiles of fluvoxamine are different from those of other drugs in its class.<ref>{{cite journal | first = Hyttel | last = J. | date = 1993 | title = Comparative pharmacology of selective serotonin reuptake inhibitors (SSRIs) | journal = Nordisk Journal of Psychiatric | volume = 47 | issue = Suppl 30 | pages = 5–12 }}</ref>
Among the SSRIs, fluvoxamine has the highest affinity for [[sigma receptor]] subtype 1 (σ<sub>1</sub>receptors),<ref>{{cite journal | first = Narita N | last = Hashimoto K et al. | date = 1996 | title = Interactions of selective reuptake inhibitors with subtypes of sigma receptor in rat brain | journal = Eur J Pharmacol| volume = 307 | issue = | pages = 117–9 | doi = 10.1016/0014-2999(96)00254-3}}</ref> suggesting that it may have particular benefits in the treatment of depressed patients who show features of anxiety/stress and for whom memory impairment is particularly undesirable (such as in depressed elderly patients, and also in treating psychotic depression).<ref>{{cite journal | first = Carrasco JL | last = C.Sandner | date = December 2005 | title = Clinical effects of pharmacological variations in selective serotonin reuptake inhibitors: an overview | journal = International Journal of Clinical Practice | volume = 59 | issue = 12 | pages = 1428–1434 | doi = 10.1111/j.1368-5031.2005.00681.x}}</ref>
==Pharmacokinetics==
{{Unreferencedsection|date=February 2008}}
===Absorption===
The oral absorption of fluvoxamine is equal to or more than 94%.
===Distribution===
The plasma protein binding is only about 76%.
===Metabolism===
Fluvoxamine is extensively metabolised in the liver. It has no active metabolites.
===Elimination===
Fluvoxamine has the shortest [[half-life]] of all the SSRIs. Its mean [[serum]] half-life is 15 hours after a single dose, and 17 to 22 hours after repeated doses.
==Drug interactions==
Fluvoxamine has a low potential for the [[drug interaction]]s which are based on inhibition of enzyme [[Cytochrome P450]] [[CYP2D6]]. Fluvoxamine shows the least interaction of the SSRIs, in regard to this specific enzyme.<ref>{{cite journal | first = Baumann | last = P. | date = 1996 | title = Pharmacokinetic-pharmacodynamic relationship of the Selective serotonin reuptake inhibitors | journal = Clinical Pharmacokinetics | volume = 31 | issue = | pages = 444–469 | doi = 10.2165/00003088-199631060-00004}}</ref><ref>{{cite journal | first = DeVane CL | last = Gill HS | date = 1997 | title = Clinical Pharmacokinetics of Fluvoxamine: applications to dosage regime design | journal = Journal of Clinical Psychiatric | volume = 58 | issue = Suppl 5 | pages = 7–14}}</ref><ref>{{cite journal | first = CL | last = DeVane| date = 1998 | title = Translational pharmacokinetics: current issues with newer antidepressants | journal = Depression and Anxiety | volume = 8 | issue = Suppl 1 | pages = 64–70 | doi = 10.1002/(SICI)1520-6394(1998)8:1+<64::AID-DA10>3.0.CO;2-S | doi_brokendate = 2008-07-07}}</ref>
Naturally the other SSRIs which are metabolized by CYP2D6 will have more CYP2D6-based interactions with TCAs, antiarrhythmics, B-blockers, phenytoin, opiates (eg. codeine, dextromethorphan, morphine, tramadol) and neuroleptics (eg. haloperidol, risperidon).
Fluvoxamine does, however, inhibit cytochrome P450 enzyme [[CYP1A2]], which metabolises [[caffeine]], [[clozapine]], [[haloperidol]], [[phenacetin]], [[tacrine]], [[theophylline]], and [[olanzapine]]. These substances can cause increased serum levels when administered together with fluvoxamine. Of major concern is the fact that the [[polycyclic aromatic hydrocarbons]] found in tobacco smoke are potent inducers of CYP1A2 so that smokers may require significant modification of medication dosage.<ref>{{cite journal| last = Kroom| first = Lisa A.| authorlink = | coauthors = | title = Drug Interactions With Smoking| journal = Am J Health-Syst Pharm.| volume = 64| issue = 18| pages = 1917–1921| publisher = American Society of Health-System Pharmacists| location = Medscape| date = 10-01-2007| url = http://www.medscape.com/viewarticle/562754_print| doi = | id = | accessdate = 2008-01-31}}</ref> A recent warning has been published regarding potentially serious interaction with [[Tizanidine]], based on CYP1A2 metabolism.<ref>{{cite web| last = Waknine| first = Yael| authorlink = | coauthors = | title = Prescribers Warned of Tizanidine Drug Interactions| work = Medscape News| publisher = Medscape| date = April 13, 2007| url = http://www.medscape.com/viewarticle/555194_print| format = | doi = | accessdate = 2008-02-01}}</ref>
Fluvoxamine inhibits metabolism of [[diazepam]] and [[phenytoin]] via [[Cytochrome P450|CYP2C19]] and inhibits metabolism of [[aripiprazole]], [[chlorpromazine]], [[clozapine]], [[haloperidol]], [[olanzapine]], [[perphenazine]], [[risperidone]], [[thioridazine]] and [[zuclopenthixol]] via [[Cytochrome P450|CYP2D6]] as well as inhibiting metabolism of [[aripiprazole]], [[clozapine]], [[haloperidol]], [[quetiapine]], [[risperidone]] and [[ziprasidone]] via [[Cytochrome P450|CYP3A4]].<ref>{{cite journal| last = Bondy| first = Brigitta| authorlink =
| coauthors = Illja Spellmann| title = Pharmacogenetics of Antipsychotics: Useful For the Clinician?
| journal = Curr Opin Psychiatry| volume = 20| issue = 1| pages = 126–130| publisher = Lippincott Williams & Wilkins| location = Medscape| date = 2007| url = http://www.medscape.com/viewarticle/552100_print| doi =
| id = | accessdate = 2008-02-01 }}</ref>
The plasma protein binding of fluvoxamine is about 77%. Drugs with low protein binding are less likely to displace other protein bound drugs, and therefore have a lower potential to cause protein binding-related drug interactions.
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==Appearance in popular culture==
The drug was given visibility in the American television series [[The Sopranos]] produced by [[HBO]], in the second season, episode 10. Dr. [[Jennifer Melfi]], the psychiatrist treating the character named [[Tony Soprano]], is prescribed Luvox by her own psychiatrist, to treat a strong inclination toward alcohol.
"Stuttering" John Melendez, formerly of The Howard Stern Show, had taken Luvox for a period of time before his departure from the show.
-->
==Notes==
{{reflist|1}}
==External links==
* [http://www.rxlist.com/cgi/generic/fluvox.htm RxList.com - Fluvoxamine]
* [http://www.drugs.com/cons/Fluvoxamine.html Drugs.com - Fluvoxamine]
{{Antidepressants}}
[[Category:Selective serotonin reuptake inhibitors]]
[[Category:Oximes]]
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