|Systematic (IUPAC) name|
|Trade names||Luvox, Floxyfral|
|Legal status||Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)|
|Bioavailability||53% (90% confidence interval: 44-62%)|
|Metabolism||Hepatic (via cytochrome P450 enzymes. Mostly via oxidative demethylation)|
|Half-life||12-13 hours (single dose), 22 hours (repeated dosing)|
|Excretion||Renal (98%; 94% as metabolites, 4% as unchanged drug)|
| (what is this?)
Fluvoxamine (brand names: Floxyfral, Luvox) is an antidepressant which functions as a selective serotonin reuptake inhibitor (SSRI) and σ1 receptor agonist. Fluvoxamine is used for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and anxiety disorders such as panic disorder and posttraumatic stress disorder (PTSD). Fluvoxamine CR (controlled release) is approved to treat social anxiety disorder.
The FDA has added a black box warning for this drug in reference to increased risks of suicidal thinking and behavior in young adults and children. A study from the Institute for Safe Medication Practices identified reports of violence from those taking fluvoxamine as being 8.4 times higher than expected given the volume of overall reports for that drug. (Five reports of violence.)
Fluvoxamine's only FDA approved indication is in the treatment of obsessive-compulsive disorder (OCD), although in other countries (e.g. Australia and the UK) it has indications for major depressive disorder as well. Fluvoxamine has been found to be useful in the treatment of major depressive disorder (MDD), and anxiety disorders such as panic disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), and obsessive-compulsive spectrum disorders. Fluvoxamine is indicated for children and adolescents with OCD. The drug works long-term, with research showing that fluvoxamine retains its therapeutic efficacy for at least a year. It has also been found to possess some analgesic properties in line with other SSRIs and tricyclic antidepressants.
There is some evidence that fluvoxamine may be a helpful adjunct in the treatment of schizophrenia, improving the depressive, negative and cognitive symptoms of the disorder. Its actions at the sigma receptor may afford it a unique advantage among antidepressants in treating the cognitive symptoms of schizophrenia.
Fluvoxamine shares a number of adverse effects with other SSRIs. These side effects include the following: Gastrointestinal side effects are more common in those receiving fluvoxamine than with other SSRIs.
- Common (1-10% incidence) adverse effects
- Anorexia (weight loss)
- Tachycardia (high heart rate)
- Abdominal pain
- Dyspepsia (indgestion)
- Dry mouth
- Hyperhidrosis (excess sweating)
- Asthenia (weakness)
- Sexual dysfunction (including delayed ejaculation, erectile dysfunction, decreased libido, etc.)
- Uncommon (0.1-1% incidence) adverse effects
- Confusional state
- Extrapyramidal side effects (e.g. dystonia, parkinsonism, tremor, etc.)
- Orthostatic hypotension
- Cutaneous hypersensitivity reactions (e.g. oedema [build up of fluid in the tissues], rash, pruritus)
- Rare (0.01-0.1% incidence) adverse effects
- Abnormal hepatic (liver) function
- Photosensitivity (being abnormally sensitive to light)
- Galactorrhoea (expulsion of breast milk that's unrelated to pregnancy or breastfeeding)
- Unknown frequency adverse effects
- Hyperprolactinaemia (elevated plasma prolactin levels leading to galactorrhoea, amenorrhoea [cessation of menstrual cycles], etc.)
- Bone fractures
- Urinary incontinence
- Urinary retention
- Serotonin syndrome — a potentially fatal condition characterised by abrupt onset muscle rigidity, hyperthermia (elevated body temperature), rhabdomyolysis, mental status changes (e.g. coma, hallucinations, agitation, etc.), etc.
- Neuroleptic malignant syndrome — practically identical presentation to serotonin syndrome except with a more prolonged onset.
- Akathisia — a sense of inner restlessness that presents itself with the inability to stay still
- Withdrawal symptoms
- Weight changes
- Suicidal ideation & behaviour
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- CYP1A2 (strongly) which metabolises agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine, etc.
- CYP3A4 (weakly) which metabolises aripiprazole, clozapine, haloperidol, quetiapine, ziprasidone, etc.
- CYP2D6 (weakly) which metabolises aripiprazole, chlorpromazine, clozapine, codeine, fluoxetine, haloperidol, olanzapine, oxycodone, paroxetine, perphenazine, pethidine, risperidone, sertraline, thioridazine, zuclopenthixol, etc.
- CYP2C9 (moderately) which metabolises Non-steroidal anti-inflammatory drugs, phenytoin, sulfonylureas, etc.
- CYP2C19 (strongly) which metabolises diazepam, phenytoin, etc.
- CYP2B6 (weakly) which metabolises bupropion, cyclophosphamide, sertraline, tamoxifen, valproate, etc.
by so doing fluvoxamine can increase serum concentration of the substrates of the aforementioned enzymes.
Fluvoxamine is a potent and selective serotonin reuptake inhibitor with approximately 100-fold affinity for the serotonin transporter over the norepinephrine transporter. It has negligible affinity for the dopamine transporter or any other receptor, with the sole exception of the σ1 receptor. It behaves as a potent agonist at this receptor and has the highest affinity of any SSRI for doing so. This may contribute to its antidepressant and anxiolytic effects and may also afford it some efficacy in treating the cognitive symptoms of depression.
Fluvoxamine was developed by Kali-Duphar, part of Solvay Pharmaceuticals, Belgium, now Abbott Laboratories, and introduced as Floxyfral in Switzerland in 1983 and Solvay in West Germany in the same year. It was approved by the FDA on 5 Dec, 1994 and introduced as Luvox in the US. In India it is available, among several other brands, as Uvox by Abbott. It was one of the first SSRI antidepressants to be launched and is prescribed to patients with major depression in many countries. It was the first SSRI, a non-TCA drug, approved by the U.S. Food and Drug Administration specifically for the treatment of OCD. At the end of 1995, more than ten million patients worldwide had been treated with fluvoxamine. Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997. In Japan, fluvoxamine was the first SSRI to be approved for the treatment of depression in 1999 and was later in 2005 the first drug to be approved for the treatment of social anxiety disorder. Fluvoxamine was the first SSRI approved for clinical use in the United Kingdom.
In 1999, fluvoxamine came under great public scrutiny after it was discovered that Eric Harris, one of the two teenage shooters involved in the Columbine High School massacre, had been taking the drug after switching from sertraline (Zoloft). Many immediately pointed fingers at fluvoxamine and its manufacturer Solvay Pharmaceuticals. Sales fell, and Solvay withdrew the medication from the U.S. market in 2002. In 2007, Solvay re-introduced Luvox to the U.S. market, which is now manufactured by Palo Alto, California-based Jazz Pharmaceuticals, Inc. On February 28, 2008, the FDA approved a controlled-release formulation of fluvoxamine for Solvay Pharmaceuticals, to be marketed as Luvox CR.
- "Luvox". ChemSpider. Royal Society of Chemistry. Retrieved 21 October 2013.
- "PRODUCT INFORMATION LUVOX®". TGA eBusiness Services. Abbott Australasia Pty Ltd. 15 January 2013. Retrieved 21 October 2013.
- "FDA Advisory Committee Recommends Luvox (Fluvoxamine) Tablets for Obsessive Compulsive Disorder," PRNewswire, 10/18/93
- Karen J. McClellan, David P. Figgitt (Drugs October 2000). "Fluvoxamine. An Updated Review of its Use in the Management of Adults with Anxiety Disorders". Adis Drug Evaluation 60 (4): 925–954.
- Stahl, S. Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press. New York, NY. 2009. pp.215
- Moore, Thomas J; Glenmullen, Joseph; Furberg, Curt D (2010), "Prescription Drugs Associated with Reports of Violence Towards Others", PLoS ONE, doi:10.1371/journal.pone.0015337
- "Fluvoxamine Maleate (fluvoxamine maleate) Tablet, Coated [Genpharm Inc.]". DailyMed. Genpharm Inc. October 2007. Retrieved 21 October 2013.
- Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. 2013. ISBN 9780980579093.
- Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 9780857110848.
- US-FDA Fluvoxamine Product Insert. March 2005.
- Wilde MI, Plosker GL, Benfield P (November 1993). "Fluvoxamine. An updated review of its pharmacology, and therapeutic use in depressive illness". Drugs 46 (5): 895–924. PMID 7507038.
- Kwasucki, J; Stepień A, Maksymiuk G, Olbrych-Karpińska B (2002). "Evaluation of analgesic action of fluvoxamine compared with efficacy of imipramine and tramadol for treatment of sciatica—open trial". Wiadomości Lekarskie 55 (1-2): 42–50. PMID 12043315.
- Schreiber, S; Pick CG (August 2006). "From selective to highly selective SSRIs: A comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram". European Neuropsychopharmacology 16 (6): 464–468. doi:10.1016/j.euroneuro.2005.11.013. PMID 16413173.
- Coquoz, D; Porchet HC, Dayer P (September 1993). "Central analgesic effects of desipramine, fluvoxamine, and moclobemide after single oral dosing: a study in healthy volunteers". Clinical Pharmacology and Therapeutics 54 (3): 339–344. doi:10.1038/clpt.1993.156. PMID 8375130.
- Wrong format. 978940075805 Number must have 10 or 13 digits. (now: 12 digits)
- Hindmarch, I; Hashimoto, K (April 2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered". Human Psychopharmacology: Clinical and Experimental 25 (3): 193–200. doi:10.1002/hup.1106. PMID 20373470.
- Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry (in English). West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
- "Faverin 100 mg film-coated tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Abbott Healthcare Products Limited. 14 May 2013. Retrieved 21 October 2013.
- Brayfield, A, ed. (13 August 2013). "Fluoxetine Hydrochloride". Martindale: The Complete Drug Reference (London, UK: Pharmaceutical Press). Retrieved 24 November 2013.
- Ciraulo, DA; Shader, RI (2011). Pharmacotherapy of Depression (2nd ed.). Springer. p. 49. doi:10.1007/978-1-60327-435-7. ISBN 978-1-60327-435-7.
- Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0071624428.
- P., Baumann (1996). "Pharmacokinetic-pharmacodynamic relationship of the Selective serotonin reuptake inhibitors". Clinical Pharmacokinetics 31 (6): 444–469. doi:10.2165/00003088-199631060-00004. PMID 8968657.
- Gill HS, DeVane CL; Gill, HS (1997). "Clinical Pharmacokinetics of Fluvoxamine: applications to dosage regime design". Journal of Clinical Psychiatry 58 (Suppl 5): 7–14. PMID 9184622.
- DeVane, CL (1998). "Translational pharmacokinetics: current issues with newer antidepressants". Depression and Anxiety 8 (Suppl 1): 64–70. doi:10.1002/(SICI)1520-6394(1998)8:1+<64::AID-DA10>3.0.CO;2-S. PMID 9809216.
- Bondy, Brigitta; Illja Spellmann (2007). "Pharmacogenetics of Antipsychotics: Useful For the Clinician?". Curr Opin Psychiatry (Medscape: Lippincott Williams & Wilkins) 20 (1): 126–130. doi:10.1097/YCO.0b013e328017f69f. PMID 17278909. Retrieved 2008-02-01.
- Kroom, Lisa A. (10-01-2007). "Drug Interactions With Smoking". Am J Health-Syst Pharm. (Medscape: American Society of Health-System Pharmacists) 64 (18): 1917–1921. doi:10.2146/ajhp060414. PMID 17823102. Retrieved 2008-01-31.
- Waknine, Yael (April 13, 2007). "Prescribers Warned of Tizanidine Drug Interactions". Medscape News. Medscape. Retrieved 2008-02-01.
- "Sigma-1 receptors and selective serotonin reuptake inhibitors: clinical implications of their relationship". Central Nervous System Agents in Medicinal Chemistry 9 (3): 197–204. September 2009. doi:10.2174/1871524910909030197. PMID 20021354.
- Sittig's Pharmaceutical Manufacturing Encyclopedia (3rd ed.). William Andrew. 2008. p. 1699. ISBN 978-0815515265. Retrieved 17 October 2013.
- "Drugs.com―Fluvoxamine". Retrieved 18 October 2013.
- "Brand Index―Fluvoxamine India". Archived from the original on 2013-10-18. Retrieved 18 October 2013.
- Omori, IM; Watanabe N; Nakagawa A; Cipriani A; Barbui C; McGuire H; Churchill R; Furukawa TA (October 2013). "Fluvoxamine versus other anti-depressive agents for depression". Cochrane Database of Systematic Reviews (9). doi:10.1002/14651858.CD006114.pub2. Retrieved 14 October 2013.
- "OCD Medication". Archived from the original on 2013-10-17. Retrieved 17 October 2013.
- Fluvoxamine Product Monograph. 1999.
- "Luvox Approved For Obsessive Compulsive Disorder in Children and Teens". Http://www.pslgroup.com/dg/2261a.htm.
- Higuchi, T; Briley, M (February 2007). "Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan". Neuropsychiatric Disease and Treatment 3 (1): 41–58. doi:10.2147/NDT.S. PMC 2654524. PMID 19300537.
- "Solvay's Fluvoxamine maleate is first drug approved for the treatment of social anxiety disorder in Japan". Http://www.solvaypress.com/pressreleases/0,,33713-2-83,00.htm.
- Walker, R; Whittlesea, C, ed. (2007) . Clinical Pharmacy and Therapeutics (4th ed.). Edinburgh: Churchill Livingstone Elsevier. ISBN 9780702042935.
- Pankratz, Howard (January 26, 2007). "Judge: Seal Columbine papers for 25 years". The Denver Post. Retrieved 2008-03-03.
- "Solvay Pharmaceuticals, Inc. Withdraws LUVOX". Http://www.solvaypharmaceuticals-us.com/newsroom/pressreleases/0,,14517-2-0,00.htm.
- "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)". Archived from the original on 2008-05-26. Retrieved 2008-03-14.
- "Luvox CR | Prescribing Info". Retrieved 2008-02-21.