|Trade names||Luvox, Faverin, Fluvoxin, others|
|Drug class||Selective serotonin reuptake inhibitors (SSRIs)|
|Bioavailability||53% (90% confidence interval: 44–62%)|
|Metabolism||Hepatic (via cytochrome P450 enzymes. Mostly via oxidative demethylation)|
|Elimination half-life||12–13 hours (single dose), 22 hours (repeated dosing)|
|Excretion||Renal (98%; 94% as metabolites, 4% as unchanged drug)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||318.335 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Fluvoxamine, sold under the brand name Luvox among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class which is used primarily for the treatment of obsessive–compulsive disorder (OCD). It is also used to treat depression and anxiety disorders, such as panic disorder, social anxiety disorder, and post-traumatic stress disorder.
Fluvoxamine is approved in the United States for OCD, and social anxiety disorder. In other countries (e.g. Australia, the UK, and Russia) it also has indications for major depressive disorder. In Japan it is currently[when?] approved to treat OCD, SAD and MDD. Fluvoxamine is indicated for children and adolescents with OCD. The drug works long-term, and retains its therapeutic efficacy for at least one year. It has also been found to possess some analgesic properties in line with other SSRIs and tricyclic antidepressants.
There is tentative evidence that fluvoxamine is effective for social phobia in adults. Fluvoxamine is also effective for GAD, SAD, panic disorder and separation anxiety disorder in children and adolescents. There is tentative evidence that fluvoxamine may help some people with negative symptoms of chronic schizophrenia.
Gastrointestinal side effects are more common in those receiving fluvoxamine than with other SSRIs. Otherwise, fluvoxamine's side-effect profile is very similar to other SSRIs.
- Common (1–10% incidence) adverse effects
- Weight loss
- Loss of appetite
- Tachycardia (high heart rate)
- Abdominal pain
- Dyspepsia (indigestion)
- Hyperhidrosis (excess sweating)
- Asthenia (weakness)
- Sexual dysfunction (including delayed ejaculation, erectile dysfunction, decreased libido, etc.)
- Xerostomia (dry mouth)
- Uncommon (0.1–1% incidence) adverse effects
- Rare (0.01–0.1% incidence) adverse effects
- Abnormal hepatic (liver) function
- Photosensitivity (being abnormally sensitive to light)
- Galactorrhoea (expulsion of breast milk 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.
- 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 and behaviour
- Violence towards others
- Syndrome of inappropriate antidiuretic hormone secretion
- CYP1A2 (strongly) which metabolizes agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine, etc.
- CYP3A4 (moderately) which metabolizes alprazolam, aripiprazole, clozapine, haloperidol, quetiapine, pimozide, ziprasidone, etc.
- CYP2D6 (moderately) which metabolizes aripiprazole, chlorpromazine, clozapine, codeine, fluoxetine, haloperidol, olanzapine, oxycodone, paroxetine, perphenazine, pethidine, risperidone, sertraline, thioridazine, zuclopenthixol, etc.
- CYP2C9 (moderately) which metabolizes nonsteroidal anti-inflammatory drugs, phenytoin, sulfonylureas, etc.
- CYP2C19 (strongly) which metabolizes clonazepam, diazepam, phenytoin, etc.
- CYP2B6 (weakly) which metabolizes bupropion, cyclophosphamide, sertraline, tamoxifen, valproate, etc.
By so doing, fluvoxamine can increase serum concentration of the substrates of these enzymes.
The plasma levels of oxidatively metabolized benzodiazepines (e.g., triazolam, midazolam, alprazolam and diazepam) are likely to be increased when co-administered with fluvoxamine. However the clearance of benzodiazepines metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine. It appears that benzodiazepines metabolized by nitro-reduction (clonazepam, nitrazepam) are unlikely to be affected by fluvoxamine. Using fluvoxamine and alprazolam together can increase alprazolam plasma concentrations. If alprazolam is coadministered with fluvoxamine, the initial alprazolam dose should be reduced to the lowest effective dose.
Fluvoxamine has been observed to increase serum concentrations of mirtazapine, which is mainly metabolized by CYP1A2, CYP2D6, and CYP3A4, by 3- to 4-fold in humans. Caution and adjustment of dosage as necessary are warranted when combining fluvoxamine and mirtazapine.
Fluvoxamine seriously affects the pharmacokinetics of tizanidine and increases the intensity and duration of its effects. Because of the potentially hazardous consequences, the concomitant use of tizanidine with fluvoxamine, or other potent inhibitors of CYP1A2, should be avoided.
Fluvoxamine is a potent selective serotonin reuptake inhibitor with around 100-fold affinity for the serotonin transporter over the norepinephrine transporter. It has negligible affinity for the dopamine transporter or any other site, with the sole exception of the σ1 receptor. It behaves as a potent agonist at this receptor and has the highest affinity (36 nM) 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. Contrary to Fluoxetine, Fluvoxamine metabolites are inactive, without a significant effect on serotonin or norepinephrine uptake. In 2019 fluvoxamine was shown to modulate the sigma-1 receptor–IRE1 pathway in mice and provide an unexpected benefit in preclinical models of inflammation and sepsis.
Fluvoxamine was developed by Kali-Duphar, part of Solvay Pharmaceuticals, Belgium, now Abbott Laboratories, and introduced as Floxyfral in Switzerland in 1983. It was approved by the U.S. Food and Drug Administration (FDA) in 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 in many countries to patients with major depression. It was the first SSRI, a non-TCA drug, approved by the U.S. FDA specifically for the treatment of OCD. At the end of 1995, more than ten million patients worldwide had been treated with fluvoxamine.[failed verification] 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. During the COVID-19 pandemic it underwent several trials of drug repurposing research against preventing cytokine storms, a complication that had arisen in severe cases of COVID-19.
Society and culture
- Clovoxamine, a chemically similar drug with a chlorine atom substituted for the CF3 substituent
- Demexiptiline, a tricyclic antidepressant with the same ketoxime termination chain as fluvoxamine
- Use During Pregnancy and Breastfeeding
- "Product Information Luvox". TGA eBusiness Services. Abbott Australasia Pty Ltd. 15 January 2013. Retrieved 21 October 2013.
- van Harten J (March 1993). "Clinical pharmacokinetics of selective serotonin reuptake inhibitors". Clinical Pharmacokinetics. 24 (3): 203–20. doi:10.2165/00003088-199324030-00003. PMID 8384945.
- "Luvox". ChemSpider. Royal Society of Chemistry. Archived from the original on 15 November 2013. Retrieved 21 October 2013.
- "Fluvoxamine Maleate Information". U.S. Food and Drug Administration (FDA). 15 July 2015. Archived from the original on 29 November 2019. Retrieved 28 November 2019.
- McCain JA (July 2009). "Antidepressants and suicide in adolescents and adults: a public health experiment with unintended consequences?". P T. 34 (7): 355–78. PMC 2799109. PMID 20140100.
- Figgitt DP, McClellan KJ (October 2000). "Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders". Drugs. 60 (4): 925–54. doi:10.2165/00003495-200060040-00006. PMID 11085201.
- Irons J (December 2005). "Fluvoxamine in the treatment of anxiety disorders". Neuropsychiatric Disease and Treatment. 1 (4): 289–99. PMC 2424117. PMID 18568110.
- "Fluvoxamine Maleate tablet, coated prescribing information". DailyMed. 14 December 2018. Retrieved 28 November 2019.
- "Luvox CR approved for OCD and SAD". MPR. 29 February 2008. Retrieved 2 March 2019.
- Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- "Luvox Tablets". NPS MedicineWise. Retrieved 22 October 2018.
- Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
- "Summary of Full Prescribing Information: Fluvoxamine". Drug Registry of Russia (RLS) Drug Compendium (in Russian). Retrieved 21 March 2015.
- "2005 News Releases". Astellas Pharma. Retrieved 16 September 2018.
- "International Approvals: Ebixa, Depromel/Luvox, M-Vax". www.medscape.com. Retrieved 16 September 2018.
- "US-FDA Fluvoxamine Product Insert". March 2005. Cite journal requires
- 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. doi:10.2165/00003495-199346050-00008. 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]". Wiadomosci 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): 464–8. 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): 339–44. doi:10.1038/clpt.1993.156. PMID 8375130.
- Williams T, Hattingh CJ, Kariuki CM, Tromp SA, van Balkom AJ, Ipser JC, Stein DJ (October 2017). "Pharmacotherapy for social anxiety disorder (SAnD)". The Cochrane Database of Systematic Reviews. 10 (10): CD001206. doi:10.1002/14651858.CD001206.pub3. PMC 6360927. PMID 29048739.
- Cheer SM, Figgitt DP (2002). "Spotlight on fluvoxamine in anxiety disorders in children and adolescents". CNS Drugs. 16 (2): 139–44. doi:10.2165/00023210-200216020-00006. PMID 11825104.
- Silver H (2001). "Fluvoxamine as an adjunctive agent in schizophrenia". CNS Drug Reviews. 7 (3): 283–304. doi:10.1111/j.1527-3458.2001.tb00200.x. PMC 6741705. PMID 11607044.
- Polcwiartek C, Nielsen J (March 2016). "The clinical potentials of adjunctive fluvoxamine to clozapine treatment: a systematic review". Psychopharmacology. 233 (5): 741–50. doi:10.1007/s00213-015-4161-1. PMID 26626327.
- Brayfield A, ed. (13 August 2013). Fluoxetine Hydrochloride. Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 24 November 2013.
- Taylor D, Paton C, Shitij K (2012). The Maudsley prescribing guidelines in psychiatry. 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.
- "Top Ten Legal Drugs Linked to Violence". Time. 7 January 2011. Retrieved 10 September 2014.
- Ciraulo DA, Shader RI (2011). Ciraulo DA, Shader RI (eds.). 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 (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
- Baumann P (December 1996). "Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors". Clinical Pharmacokinetics. 31 (6): 444–69. doi:10.2165/00003088-199631060-00004. PMID 8968657.
- DeVane CL, Gill HS (1997). "Clinical pharmacokinetics of fluvoxamine: applications to dosage regimen design". The Journal of Clinical Psychiatry. 58 Suppl 5 (Suppl 5): 7–14. PMID 9184622.
- DeVane CL (1998). "Translational pharmacokinetics: current issues with newer antidepressants". Depression and Anxiety. 8 Suppl 1 (Suppl 1): 64–70. doi:10.1002/(SICI)1520-6394(1998)8:1+<64::AID-DA10>3.0.CO;2-S. PMID 9809216.
- Bondy B, Spellmann I (March 2007). "Pharmacogenetics of antipsychotics: useful for the clinician?". Current Opinion in Psychiatry. 20 (2): 126–30. doi:10.1097/YCO.0b013e328017f69f. PMID 17278909.
- Kroon LA (September 2007). "Drug interactions with smoking". American Journal of Health-System Pharmacy. 64 (18): 1917–21. doi:10.2146/ajhp060414. PMID 17823102.
- Waknine Y (13 April 2007). "Prescribers Warned of Tizanidine Drug Interactions". Medscape News. Medscape. Retrieved 1 February 2008.
- "Fluvoxamine (Oral Route) Precautions". Mayo Clinic. Retrieved 2 November 2018.
- Hemeryck A, Belpaire FM (February 2002). "Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update". Current Drug Metabolism. 3 (1): 13–37. doi:10.2174/1389200023338017. PMID 11876575.
- Raouf (2016). "Benzodiazepine Metabolism and Pharmacokinetics" (PDF). reviewed and edited by Dr. Jeffrey Fudin.
- Peppers MP (1996). "Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease". Pharmacotherapy. 16 (1): 49–57. doi:10.1002/j.1875-9114.1996.tb02915.x (inactive 21 May 2020). PMID 8700792.
- "fluvoxamine maleate: PRODUCT MONOGRAPH" (PDF). 2016.
- "Luvox Data Sheet" (PDF). Medsafe, New Zealand. 2017.
- Suzuki Y, Shioiri T, Muratake T, Kawashima Y, Sato S, Hagiwara M, Inoue Y, Shimoda K, Someya T (April 2003). "Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles". European Journal of Clinical Pharmacology. 58 (12): 829–33. doi:10.1007/s00228-003-0563-9. PMID 12698310.
- Gerlach, Manfred, Warnke, Andreas, Greenhill, Laurence (2014). Psychiatric Drugs in Children and Adolescents: Basic Pharmacology and Practical Applications. Springer-Verlag Wien. p. 131. ISBN 978-3-7091-1500-8.
- Fleishaker JC, Hulst LK (1994). "A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine". European Journal of Clinical Pharmacology. 46 (1): 35–9. doi:10.1007/bf00195913. PMID 8005185.
- Obach RS, Ryder TF (August 2010). "Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics". Drug Metabolism and Disposition. 38 (8): 1381–91. doi:10.1124/dmd.110.034009. PMID 20478852.
- Pandi-Perumal SR, Spence DW, Verster JC, Srinivasan V, Brown GM, Cardinali DP, Hardeland R (12 April 2011). "Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications". Journal of Central Nervous System Disease. 3: 51–65. doi:10.4137/JCNSD.S1611. PMC 3663615. PMID 23861638.
- Anttila AK, Rasanen L, Leinonen EV (October 2001). "Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold". The Annals of Pharmacotherapy. 35 (10): 1221–3. doi:10.1345/aph.1A014. PMID 11675851.
- Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ (April 2004). "Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction". Clinical Pharmacology and Therapeutics. 75 (4): 331–41. doi:10.1016/j.clpt.2003.12.005. PMID 15060511.
- Ishikawa M, Ishiwata K, Ishii K, Kimura Y, Sakata M, Naganawa M, Oda K, Miyatake R, Fujisaki M, Shimizu E, Shirayama Y, Iyo M, Hashimoto K (October 2007). "High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503". Biological Psychiatry. 62 (8): 878–83. doi:10.1016/j.biopsych.2007.04.001. PMID 17662961.
- Schatzberg AF, Nemeroff CB (2009). The American Psychiatric Publishing textbook of psychopharmacology (4th ed.). Arlington, VA: American Psychiatric Pub. p. 354. ISBN 978-1-585-62386-0. OCLC 320111564.
- Yahata, Masahiro; Chiba, Koji; Watanabe, Takao; Sugiyama, Yuichi (September 2017). "Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma Concentration of Unbound Drugs, and Their Profiles for Substrates of Transporters". Journal of Pharmaceutical Sciences. 106 (9): 2345–2356. doi:10.1016/j.xphs.2017.05.007. ISSN 1520-6017. PMID 28501470.
- Hashimoto K (September 2009). "Sigma-1 receptors and selective serotonin reuptake inhibitors: clinical implications of their relationship". Central Nervous System Agents in Medicinal Chemistry. 9 (3): 197–204. doi:10.2174/1871524910909030197. PMID 20021354.
- Westenberg HG, Sandner C (April 2006). "Tolerability and safety of fluvoxamine and other antidepressants". International Journal of Clinical Practice. 60 (4): 482–91. doi:10.1111/j.1368-5031.2006.00865.x. PMC 1448696. PMID 16620364.
- Hindmarch I, Hashimoto K (April 2010). "Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered". Human Psychopharmacology. 25 (3): 193–200. doi:10.1002/hup.1106. PMID 20373470.
- Hrdina PD (July 1991). "Pharmacology of serotonin uptake inhibitors: focus on fluvoxamine". Journal of Psychiatry & Neuroscience. 16 (2 Suppl 1): 10–8. PMC 1188307. PMID 1931931.
- Sittig's Pharmaceutical Manufacturing Encyclopedia (PDF) (3rd ed.). William Andrew. 2008. p. 1699. ISBN 978-0-8155-1526-5. Retrieved 17 October 2013.
- Leslie LK, Newman TB, Chesney PJ, Perrin JM (July 2005). "The Food and Drug Administration's deliberations on antidepressant use in pediatric patients". Pediatrics. 116 (1): 195–204. doi:10.1542/peds.2005-0074. PMC 1550709. PMID 15995053.
- "Brand Index―Fluvoxamine India". Archived from the original on 19 October 2013. Retrieved 18 October 2013.
- Omori IM, Watanabe N, Nakagawa A, Cipriani A, Barbui C, McGuire H, Churchill R, Furukawa TA (March 2010). "Fluvoxamine versus other anti-depressive agents for depression". The Cochrane Database of Systematic Reviews (3): CD006114. doi:10.1002/14651858.CD006114.pub2. PMC 4171125. PMID 20238342.
- "OCD Medication". Archived from the original on 14 October 2013. Retrieved 17 October 2013.
- "Fluvoxamine Product Monograph" (PDF). 1999.
- "Luvox Approved For Obsessive Compulsive Disorder in Children and Teens". Archived from the original on 16 January 2009. Retrieved 8 February 2014.
- 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/nedt.2007.3.1.41. PMC 2654524. PMID 19300537.
- "Human Metabolome Database: Showing metabocard for Fluvoxamine (HMDB0014322)". www.hmdb.ca. Retrieved 15 September 2018.
- "Solvay's Fluvoxamine maleate is first drug approved for the treatment of social anxiety disorder in Japan".
- Walker R, Whittlesea C, eds. (2007) . Clinical Pharmacy and Therapeutics (4th ed.). Edinburgh: Churchill Livingstone Elsevier. ISBN 978-0-7020-4293-5.
- "Study to evaluate antidepressant as potential COVID-19 treatment". Washington University School of Medicine in St. Louis. 13 April 2020. Retrieved 22 June 2020.
- "Fluvoxamine". www.drugbank.ca. Retrieved 22 October 2019.
- "0 - The Express Wire". www.theexpresswire.com.
- "Fluvoxamine". Drug Information Portal. U.S. National Library of Medicine.