Fluvoxamine

Not to be confused with Fluoxetine.

Fluvoxamine

Systematic (IUPAC) name
2-{[(E)-{5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene}amino]oxy}ethanamine
Clinical data
Trade names	Faverin, Fevarin, Floxyfral, Luvox
AHFS/Drugs.com	monograph
MedlinePlus	a682275
Pregnancy category	C
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	53% (90% confidence interval: 44-62%)
Protein binding	80%
Metabolism	Hepatic (via cytochrome P450 enzymes. Mostly via oxidative demethylation)
Biological half-life	12-13 hours (single dose), 22 hours (repeated dosing)
Excretion	Renal (98%; 94% as metabolites, 4% as unchanged drug)
Identifiers
CAS Number	54739-18-3 Y
ATC code	N06AB08 (WHO)
PubChem	CID: 5324346
IUPHAR/BPS	7189
DrugBank	DB00176 N
ChemSpider	4481878 Y
UNII	O4L1XPO44W Y
KEGG	D07984 Y
ChEBI	CHEBI:5138 Y
ChEMBL	CHEMBL814 Y
Chemical data
Formula	C15H21F3N2O2
Molecular mass	318.335
SMILES FC(F)(F)c1ccc(\C(=N\OCCN)CCCCOC)cc1
InChI InChI=1S/C15H21F3N2O2/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18/h5-8H,2-4,9-11,19H2,1H3/b20-14+ Y Key:CJOFXWAVKWHTFT-XSFVSMFZSA-N Y
NY (what is this?)  (verify)

Fluvoxamine (brand names: Faverin, Fevarin, Floxyfral, and Luvox) is a medication which functions as a selective serotonin reuptake inhibitor (SSRI) and σ₁ receptor agonist. Fluvoxamine is used primarily for the treatment of obsessive-compulsive disorder (OCD), and is also used to treat major depressive disorder (MDD), and anxiety disorders such as panic disorder and post-traumatic 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.

Medical uses

Fluvoxamine's only FDA approved indication is in the treatment of OCD, although in other countries (e.g. Australia, UK and Russian Federation) it has indications for MDD, as well. Fluvoxamine has been found to be useful in the treatment of 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, and 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.

Some evidence shows 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.

Adverse effects

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

• Nausea
• Vomiting
• Anorexia (weight loss)
• Agitation
• Nervousness
• Anxiety
• Insomnia
• Somnolence
• Tremor
• Headache
• Dizziness
• Palpitations
• Tachycardia (high heart rate)
• Abdominal pain
• Dyspepsia (indigestion)
• Diarrhoea
• Constipation
• Dry mouth
• Hyperhidrosis (excess sweating)
• Asthenia (weakness)
• Malaises
• Sexual dysfunction (including delayed ejaculation, erectile dysfunction, decreased libido, etc.)

Uncommon (0.1-1% incidence) adverse effects

• Hallucination
• Confusional state
• Extrapyramidal side effects (e.g. dystonia, parkinsonism, tremor, etc.)
• Orthostatic hypotension
• Cutaneous hypersensitivity reactions (e.g. oedema [buildup of fluid in the tissues], rash, pruritus)
• Arthralgia

Rare (0.01-0.1% incidence) adverse effects

• Mania
• Seizures
• 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
• Glaucoma
• Mydriasis
• Urinary incontinence
• Urinary retention
• Bed-wetting
• 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
• Paraesthesia
• Dysgeusia
• Haemorrhage
• Withdrawal symptoms
• Weight changes
• Suicidal ideation and behaviour
• Violence towards others
• Hyponatraemia
• Syndrome of inappropriate antidiuretic hormone secretion

Interactions

Fluvoxamine inhibits the following cytochrome P450 enzymes:

• CYP1A2 (strongly) which metabolizes agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine, etc.
• CYP3A4 (weakly) which metabolizes alprazolam, aripiprazole, clozapine, haloperidol, quetiapine, ziprasidone, etc.
• CYP2D6 (weakly) 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.

Pharmacology

Fluvoxamine is a potent and 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 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.

History

Fluvoxamine was developed by Kali-Duphar, part of Solvay Pharmaceuticals, Belgium, now Abbott Laboratories, and introduced as Floxyfral in Switzerland and Solvay in West Germany in 1983. 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 in many countries to patients with major depression. It was the first SSRI, a nonTCA 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. 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.

See also

• Diphenhydramine
• Demexiptiline the termination chain is the same

External links

• Fluvoxamine consumer information from Drugs.com

• "FDA Advisory Committee Recommends Luvox (Fluvoxamine) Tablets for Obsessive Compulsive Disorder," PRNewswire, 10/18/93
• Stahl, S. Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press. New York, NY. 2009. pp.215