Fluvoxamine

Structural formula
General
Non-proprietary name	Fluvoxamine
other names	( E ) -5-methoxy-1- [4- (trifluoromethyl) phenyl] pentan-1-one- [ O - (2-aminoethyl) oxime] ( IUPAC ) Fluvoxaminum ( Latin )
Molecular formula	C 15 H 21 F 3 N 2 O 2
External identifiers / databases
CAS number 54739-18-3 (free base) 61718-82-9 (hydrogen maleate ) EC number 611-193-1 ECHA InfoCard 100.125.476 PubChem 5324346 DrugBank DB00176 Wikidata Q409236
Drug information
ATC code	N06 AB08
Drug class	Antidepressants
Mechanism of action	Selective serotonin reuptake inhibitor
properties
Molar mass	318,33 g · mol -1 (free base) 434.41 g · mol -1 (hydrogen maleate)
Physical state	firmly
Melting point	120-121.5 ° C (hydrogen maleate )
pK s value	8.7 (hydrogen maleate)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302 P: no P-phrases
Toxicological data	1100 mg kg −1 ( LD 50 ,  mouse ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fluvoxamine is an antidepressant from the group of selective serotonin reuptake inhibitors (SSRIs). It is particularly used to treat obsessive-compulsive disorder , but less often also for depression or anxiety disorders.

Especially when compared to citalopram, fluoxetine, or other SSRIs, fluvoxamine is rather unpopular today.

development

Fluvoxamine was developed by the pharmaceutical company Solvay . From 1983 it was tested in clinical studies on around 35,000 patients and then first introduced in Switzerland a year later. This was followed by approval in the USA in 1994 and in Japan in 1999. In 1995 over 10 million patients were treated with fluvoxamine.

application areas

Fluvoxamine is approved in Germany for the treatment of depression and obsessive-compulsive disorder . It is also used off-label for generalized anxiety disorder , social phobia , post-traumatic stress disorder , panic disorder or irritable bowel syndrome .

Contraindications

Fluvoxamine must not be used in combination therapy with an MAO inhibitor . If you switch from an MAOI to fluvoxamine, you have to wait 2 weeks for irreversible MAOIs; for reversible MAOIs such as moclobemide the waiting time is 1 day.

When switching from fluvoxamine to an MAOI, a waiting period of 1 week must be observed. Concomitant administration of fluvoxamine with tizanidine is contraindicated.

pharmacology

Fluvoxamine binding profile

receptor	K i (nM)
SERT	11
NET	1119
5-HT 2C	5786
α 1	1288
σ 1	36

Fluvoxamine differs from most other SSRIs in its monocyclic chemical structure. Nevertheless, it works just like all other SSRIs in that it only selectively inhibits the reuptake of serotonin ( SERT ), but hardly affects the reuptake of norepinephrine and dopamine .

It also has hardly any anticholinergic or antihistamine properties. Fluvoxamine also acts in high concentrations as FIASMA (functional inhibitor of acid sphingomyelinase ).

particularities

A special feature of fluvoxamine is its high affinity for the σ-receptor , which is particularly advantageous in the treatment of delusional or anxious depression.

The half-life of fluvoxamine is relatively short at 15 hours.

Therapeutically sensible doses are between 50 and 300 mg per day .

unwanted effects

Fluvoxamine has the typical side effects of SSRIs . The negative effects on libido and sexual side effects are said to be less pronounced.

The following undesirable side effects can be observed:

• Nervous system

Common: agitation, anxiety, drowsiness, insomnia, tremors, somnolence , nervousness

Uncommon: ataxia, states of confusion, extrapyramidal symptoms, hallucinations

Rare: convulsions, mania

• Cardiovascular system

Common: palpitations, tachycardia, long QT (U) syndrome (LQT (U))

Uncommon: orthostatic hypotension

Rare: symptomatic cardiac arrhythmia with LQT (U) syndrome (especially when combined with clozapine)

• Digestive tract

Common: Abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia

Rare: liver dysfunction

• skin

Common: sweating.

Uncommon: hypersensitivity reactions (including rash, pruritus, angioedema).

Rare: photosensitivity.

• Skeletal muscles

Uncommon: joint pain, muscle pain.

• Reproductive system and breast

Uncommon: impotence, anorgasmia, libido disorders, abnormal (delayed) ejaculation.

Rare: galactorrhea

• Other undesirable effects

Common: asthenia, headache, malaise

A rare side effect is the so-called serotonin syndrome , which occurs especially when combined with certain other centrally acting drugs (see below). It manifests itself through clouding of consciousness, muscle rigidity, muscle tremors, twitching and fever. If these symptoms occur, patients should inform their doctor immediately.

Interactions

Fluvoxamine works by blocking various cytochrome P450 enzymes in the liver. This will slow down the breakdown of fluvoxamine and other drugs:

• CYP1A2 (heavily) metabolizes agomelatine , amitriptyline , caffeine , clomipramine , clozapine , duloxetine , haloperidol , imipramine , phenacetine , tacrine , tamoxifen , theophylline , olanzapine ,
• CYP3A4 (weakly) metabolizes alprazolam , aripiprazole , clozapine, haloperidol, quetiapine , ziprasidone , among others ,
• CYP2D6 (weakly) metabolizes aripiprazole, chlorpromazine , clozapine, codeine , fluoxetine , haloperidol, olanzapine, oxycodone , paroxetine , perphenazine , pethidine , risperidone , sertraline , thioridazine , zuclopenthixol ,
• CYP2C9 (moderately) metabolizes NSAID , phenytoin , sulfonylurea ,
• CYP2C19 (heavily) metabolizes clonazepam , diazepam , phenytoin,
• CYP2B6 (weakly) metabolizes bupropion , cyclophosphamide , sertraline, tamoxifen, valproate, among others .

With SSRIs such as fluvoxamine, the simultaneous intake of drugs with an effect on the serotonin system (e.g. MAO inhibitors , tryptophan , 5-HTP , lithium , triptans , St. John's wort ) can reduce the risk of the rare but potentially life-threatening serotonin syndrome increase.

Fluvoxamine can increase the plasma concentrations of carbamazepine . The plasma levels of oxidatively metabolized benzodiazepines (e.g. alprazolam , diazepam , bromazepam , brotizolam , midazolam , triazolam ) may be increased with concomitant use of fluvoxamine.

application

With food and drink

If possible, alcohol should not be drunk during treatment with fluvoxamine.

Fluvoxamine can reduce caffeine excretion by up to five times. Patients should therefore limit their caffeine consumption.

During pregnancy

See also: SSRI and pregnancy

In the absence of controlled clinical studies in pregnant women, fluvoxamine should only be used in women of childbearing potential if absolutely necessary and an appropriate contraceptive used. Withdrawal symptoms are possible in newborns whose mothers took fluvoxamine: eating and sleeping disorders, breathing difficulties, seizures, temperature changes, hypoglycemia, tremor, abnormal muscle tone, hyperreflexia, vomiting, abnormal irritability, and prolonged crying.

In children and adolescents

Fluvoxamine should not be used to treat depression in patients under 18 years of age. Suicidality and hostile behavior have been observed in clinical studies. Occasional behavioral disorders have also been reported in children with obsessive-compulsive disorder taking fluvoxamine. The patient should be carefully monitored. Long-term data on the safety of fluvoxamine with respect to growth, maturation, intelligence development and behavioral development in patients of these age groups are not available.

Possible intensification of suicidal thoughts

Suicidal ideation and behavior may increase, especially in children and adolescents. Patients should be closely monitored for signs of worsening depression, particularly suicidal behavior and restlessness, especially at the start of treatment and when changing dose. Patients must be closely monitored even after treatment has been discontinued, as such symptoms can appear as signs of withdrawal or the onset of relapse.

Withdrawal syndrome

→ Main article : SSRI withdrawal syndrome

When fluvoxamine is stopped abruptly, some patients have experienced withdrawal phenomena such as paresthesia , headache, nausea , dizziness, tiredness, difficulty sleeping and anxiety. These are usually mild and go away on their own and are not signs of addiction. Treatment may only be discontinued after consulting a doctor.

Trade names

Monopreparations

Fevarin (D), Flox-Ex (CH), Floxyfral (A, CH), Luvox (AU), various generics (D)

Individual evidence

1. ^ The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, pp. 722-723, ISBN 978-0-911910-00-1 .
2. ↑ Entry on fluvoxamine. In: Römpp Online . Georg Thieme Verlag, accessed on September 30, 2014.
3. ↑ ^{a b c} Datasheet Fluvoxamine maleate from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).
4. ↑ Specialist information from the Swiss Medicines Compendium; Information for the drug Floxyfral, April 2008.
5. ↑ MJ Owens, DL Knight, CB Nemeroff: Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. . In: Biological Psychiatry . 50, No. 5, September 1, 2001, pp. 345-50. doi : 10.1016 / s0006-3223 (01) 01145-3 . PMID 11543737 .
6. ↑ J. Kornhuber, M. Muehlbacher, S. Trapp, S. Pechmann, A. Friedl, M. Reichel, C. Mühle, L. Terfloth, T. Groemer, G. Spitzer, K. Liedl, E. Gulbins, P Tripal: Identification of Novel Functional Inhibitors of Acid Sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 . PMID 18504571 .
7. ↑ ^{a b c d e} Specialist information of the Swiss Medicines Compendium: Floxyfral, as of December 2005.
8. ↑ JT Milnes et al .: Blockade of HERG potassium currents by fluvoxamine . In: Br J Pharmacol , 2003 Jul, 139, No. 5, pp. 887-898.
9. ↑ ^{a b} A. M. Nia, KM Dahlem, N. Gassanov, H. Hungerbühler, U. Fuhr, F. Er: Clinical impact of fluvoxamine-mediated long QTU syndrome . In: Eur J Clin Pharmacol , 2012, 68, pp. 109-111, PMID 21713517
10. ↑ DA Ciraulo, RI Shader: Pharmacotherapy of Depression , 2nd. Edition, Springer, 2011, ISBN 978-1-60327-435-7 , p. 49, doi : 10.1007 / 978-1-60327-435-7 .
11. ↑ L. Brunton, B. Chabner, B. Knollman: Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th ed. McGraw-Hill Professional, New York 2010, ISBN 978-0-07-162442-8 .
12. ↑ Baumann P .: Pharmacokinetic-pharmacodynamic relationship of the Selective serotonin reuptake inhibitors . In: Clinical Pharmacokinetics . 31, No. 6, 1996, pp. 444-469. doi : 10.2165 / 00003088-199631060-00004 . PMID 8968657 .
13. ↑ CL DeVane, HS Gill: Clinical Pharmacokinetics of Fluvoxamine: Applications to dosage regime design . In: Journal of Clinical Psychiatry . 58, No. Suppl 5, 1997, pp. 7-14. PMID 9184622 .
14. ↑ CL Devane: Translational pharmacokinetics: current issues with newer antidepressants . In: Depression and Anxiety . 8, No. Suppl 1, 1998, pp. 64-70. doi : 10.1002 / (SICI) 1520-6394 (1998) 8: 1+ <64 :: AID-DA10> 3.0.CO; 2-S . PMID 9809216 .
15. ↑ Brigitta Bondy, Illja Spellmann: Pharmacogenetics of Antipsychotics: Useful For the Clinician? . In: Lippincott Williams & Wilkins (Eds.): Curr Opin Psychiatry . 20, No. 1, Medscape, 2007, pp. 126-130. doi : 10.1097 / YCO.0b013e328017f69f . PMID 17278909 . Retrieved February 1, 2008.
16. ↑ Lisa A. Kroom: Drug Interactions With Smoking . In: American Society of Health-System Pharmacists (Ed.): Am J Health Syst Pharm . 64, No. 18, Medscape, Jan 10, 2007, pp. 1917-1921. doi : 10.2146 / ajhp060414 . PMID 17823102 . Retrieved January 31, 2008.
17. ↑ Yael Waknine: Prescribers Warned of Tizanidine Drug Interactions . In: Medscape News . Medscape. April 13, 2007. Retrieved February 1, 2008.
18. ^ Specialist information of the Swiss Medicines Compendium: Carsol CR; Information as of January 2004.
19. ↑ Technical information of the Swiss drug compendium: Floxyfral® junior 50 mg / Floxyfral® 100 mg, information as of April 2008.
20. ↑ Technical information on "Fevarin 50 mg film-coated tablets" from February 2008.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !