Fluvoxamine

Systematic (IUPAC) name
(E)-5-methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one O-2-aminoethyl oxime
Identifiers
CAS number	54739-18-3
ATC code	N06AB08
PubChem	CID 5324346
DrugBank	APRD00425
ChemSpider	4481878
Chemical data
Formula	C15H21F3N2O2
Mol. mass	318.335
Pharmacokinetic data
Bioavailability	77%
Metabolism	Hepatic
Half-life	15.6 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C
Legal status	Prescription Only (S4) (AU) ?-only (US)
Routes	Oral
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Fluvoxamine (brand name Luvox) is an antidepressant which functions as a selective serotonin reuptake inhibitor (SSRI). Fluvoxamine was first approved by the U.S. Food and Drug Administration (FDA) in 1993 for the treatment of obsessive compulsive disorder (OCD).^[1] Fluvoxamine is also prescribed to treat major depression, and anxiety disorders such as generalized anxiety disorder (GAD), panic disorder, social phobia, and post-traumatic stress disorder (PTSD).^[2]

[edit] History

Fluvoxamine was developed by Solvay Pharmaceuticals and was the first non-TCA drug approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of OCD.^[3] It was one of the first SSRI antidepressants to be launched (1984 in Switzerland), and following its FDA approval in 1993, it was launched in the U.S. in December 1994, Australia in February 1999 and Japan in June 1999.^[4]

At the end of 1995, more than 10 million patients worldwide had been treated with fluvoxamine.^[5]

Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997.^[6]

Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.^[7]

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. Many immediately pointed fingers at fluvoxamine and its manufacturer Solvay Pharmaceuticals.^[8] Sales fell, and Solvay withdrew the medication from the U.S. market in 2002.^[9]

In 2007, Solvay re-introduced Luvox to the U.S., which is now manufactured by Palo Alto, California-based Jazz Pharmaceuticals, Inc. A generic version of Luvox is available from IVAX Pharmaceuticals, Inc.

On February 28, 2008, the FDA approved a controlled-release formulation of fluvoxamine, to be marketed as Luvox CR.^[10][11]

[edit] Indications

Fluvoxamine is widely prescribed to treat major depressive disorder, and anxiety disorders such as obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD), panic disorder, social phobia, and post-traumatic stress disorder (PTSD). Fluvoxamine is indicated for children and adolescents with OCD.^[12]

[edit] Unapproved/off-label/investigational

Fluvoxamine may help in the treatment of Irritable Bowel Syndrome.^[13]

[edit] Side effects

Luvox 100 mg scored tablets (AU)

Side effects most commonly observed with fluvoxamine include nausea, vomiting, drowsiness, difficulty sleeping, dizziness, nervousness, feeling anxious, dry mouth, abdominal pain, constipation, diarrhea, heart burn, loss of appetite, muscle weakness, pins and needles, abnormal taste, headache, faster heart beat, sweating, weight gain, weight loss or unusual bruising. Other side effects which are observed more frequently in children include abnormal thoughts or behaviour, cough, increased period pain, nose bleeds, increased restlessness, infection and sinusitis.^[14][15]

Sexual side effects with fluvoxamine are less pronounced than with other SSRIs.^[16][17][18]

[edit] Pharmacology

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 sigma-s₁ 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. Indeed, other SSRIs which also act as sigma-s₁ receptor agonists, such as sertraline and escitalopram (not verified but likely to be), display enhanced antidepressant efficacy.^[19] 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).^[20] In fact, the TCA opipramol, a sigma-s₁ receptor agonist without effects on the serotonin, dopamine, or norepinephrine systems, has considerable antidepressant and efficacy in its own right.

[edit] Pharmacokinetics

[edit] Absorption

The oral absorption of fluvoxamine is equal to or more than 94%.

[edit] Distribution

The plasma protein binding is only about 76%.

[edit] Metabolism

Fluvoxamine is strongly metabolized in the liver, mostly by the processes of oxidative demethylation(1) and deaminiation(2), which, respectively, create the three metabolites: fluvoxamine acid(by mechanism 1), it's N-acytylated analog(1), fluvoxethanol(2), of which only the first has been shown to have an affinity as a SERT inhibitor, roughly 100% - 200%, or 1-2 orders of magnitude, less potent than the active parent compound.^[21]

Radio-labeled administration of a dose of fluvoxamine produced nine identifiable metabolites, constituting 85% of the absorbed dosage. Of this base parent-metabolic percentage, 60% of the isolate was empirically proven to be fluvoxamine acid, and it's N-acytylated analog, 10% fluvoxethanol, logically deducible is that the additional 15% consisted of the remaining six identified metabolites of the parent compound.^[21]

[edit] Elimination

Fluvoxamine has the shortest half-life of all SSRIs; its mean serum half-life is 15.6 hours.^[22]

[edit] Drug interactions

Fluvoxamine has a low potential for the drug interactions which are based on inhibition of enzyme Cytochrome P450 CYP2D6. Fluvoxamine shows the least interaction of the SSRIs, in regard to this specific enzyme.^[23][24][25] Naturally the other SSRIs which are metabolized by CYP2D6 will have more CYP2D6-based interactions with TCAs, antiarrhythmics, B-blockers, phenytoin, opioids (e.g. codeine, morphine, tramadol) and neuroleptics (e.g. haloperidol, [risperidone).

Fluvoxamine does, however, inhibit cytochrome P450 enzyme CYP1A2, which metabolises agomelatine, 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.^[26] A recent warning has been published regarding potentially serious interaction with tizanidine, based on CYP1A2 metabolism.^[27]

Fluvoxamine inhibits metabolism of diazepam and phenytoin via CYP2C19 and metabolism of aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, perphenazine, risperidone, thioridazine and zuclopenthixol via CYP2D6 as well as of aripiprazole, clozapine, haloperidol, quetiapine, risperidone and ziprasidone via CYP3A4.^[28]

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.

Fluvoxamine also inhibits CYP2C9.^[21][29]

[edit] Chemistry

Fluvoxamine is one of the few SSRIs to have a monocyclic structure. ^[30]

[edit] Notes

[edit] External links

• RxList.com – Fluvoxamine
• Drugs.com – Fluvoxamine

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Fluvoxamine".