Fluvoxamine

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Fluvoxamine
Systematic (IUPAC) name
2-[(5-methoxy-1- [4-(trifluoromethyl) phenyl]pentylidene) amino]oxyethanamine
Identifiers
CAS number 54739-18-3
ATC code N06AB08
PubChem 5324346
DrugBank APRD00425
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

℞-only(US)
Routes Oral

Fluvoxamine (Luvox) is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. Though it is in the same class as other SSRI drugs, it is most often used to treat obsessive-compulsive disorder.

Contents

[edit] History

Fluvoxamine was one of the first of the SSRI antidepressants to be launched (1984 - Switzerland) and was developed by Solvay Pharmaceuticals. It was launched in the US in December 1994 and in Japan in June 1999. As of the end of 1995, more than 10 million patients worldwide have been treated with fluvoxamine.[1] 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.[2] Sales fell, and Solvay withdrew the medication from the U.S. market in 2002. In 2007 Solvay re-introduced Luvox, which is now manufactured by Palo Alto, California-based Jazz Pharmaceuticals Inc.

Fluvoxamine was the first SSRI to be registered for the treatment of Obsessive Compulsive Disorder in children by FDA in 1997.[3]

Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.[4]

On February 28, 2008, the US FDA approved a controlled-release formulation of fluvoxamine, to be marketed in the US as LUVOX CR. [5]

[edit] Indication

[edit] Approved

Fluvoxamine is widely prescribed to treat depression, and anxiety disorders such as Obsessive-Compulsive Disorder, Obsessive-Compulsive Spectrum Disorder, Panic Disorder, Social Phobia, and Post-Traumatic Stress Disorder.[6]

Fluvoxamine is indicated for children and adolescents with OCD.[7]

[edit] Unapproved/Off-label/Investigational

Fluvoxamine is also used for the treatment of children and adolescents with social phobia, separation anxiety disorder, or generalized anxiety disorder.[8]

Fluvoxamine may help in the treatment of Irritable Bowel Syndrome.[9]

[edit] Mode of Action

Fluvoxamine is one of the few SSRI class of drugs to have a monocyclic structure.

Although all SSRIs inhibit the reuptake of serotonin, fluvoxamine has different pharmacological and side effects profiles from other drugs in its class. [10]

Among the SSRIs, fluvoxamine has the highest affinity for sigma receptor subtype 1 (σ1receptors)[11] , 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).[12]

[edit] Pharmacokinetics

 This section does not cite any references or sources. (February 2008)
Please help improve this section by adding citations to reliable sources. Unverifiable material may be challenged and removed.

[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 extensively metabolised in the liver. It has no active metabolites.

[edit] Elimination

Fluvoxamine has the shortest half-life of all the SSRIs. Its mean serum half-life is 15 hours after a single dose, and 17 to 22 hours after repeated doses.

[edit] Dosage & Administration

The normal dosage for depression and anxiety starts at 50mg per day, rising to 100mg after a few days. It may be raised after evaluation of the effects by a doctor.

Fluvoxamine has shown generally effective for OCD at 150mg and above, and dosages can reach 300mg or more for some patients.

[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.[13][14][15] Naturally the other SSRIs which are metabolized by CYP2D6 will have more CYP2D6-based interactions with TCAs, antiarrhythmics, B-blockers, phenytoin, opiates (eg. codeine, dextromethorphan, morphine, tramadol) and neuroleptics (eg. haloperidol, risperidon).

Fluvoxamine does, however, inhibit Cytochrome P450 enzyme CYP1A2, which metabolises 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.[16] A recent warning has been published regarding potentially serious interaction with Tizanidine, based on CYP1A2 metabolism.[17]

Fluvoxamine inhibits metabolism of diazepam and phenytoin via CYP2C19 and inhibits metabolism of aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, perphenazine, risperidone, thioridazine and zuclopenthixol via CYP2D6 as well as inhibiting metabolism of aripiprazole, clozapine, haloperidol, quetiapine, risperidone and ziprasidone via CYP3A4.[18]

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.

[edit] Side effects

Side effects of fluvoxamine can include: decreased sex drive or ability, drowsiness, tiredness, diarrhea, dizziness or light-headedness, constipation, headache, nausea, nervousness, sleep problems, increased sweating, tremors, serious skin rash, vomiting, stomach pain, dry mouth, heart burn, loss of appetite, pins and needles, abnormal taste, increased heart beat, weight gain or loss, unusual bruising and other allergic problems such as difficulty breathing, fever, confusion, severe weakness, intense agitation or anxiety, restlessness, hypomania, mania, seizures.

Fluvoxamine has been found to delay ejaculation in a manner similar to but less than other SSRIs including fluoxetine, paroxetine and sertraline. Sexual dysfunction and anorgasmia is quite rare side effect with fluvoxamine, contrary to other SSRIs. [19][20]


[edit] Notes

  1. ^ "" (1999). Fluvoxamine Product Monograph. 
  2. ^ Judge: Seal Columbine papers for 25 years - The Denver Post. Retrieved on 2008-03-03.
  3. ^ "Luvox Approved For Obsessive Compulsive Disorder in Children and Teens" . http://www.pslgroup.com/dg/2261a.htm. 
  4. ^ "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. 
  5. ^ 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). Retrieved on 2008-03-14.
  6. ^ Karen J. McClellan, David P. Figgit (Drugs Oct 2000). "Fluvoxamine An Updated Review of its Use in the Management of Adults with Anxiety Disorders". Adis Drug Evaluation 60 (4): 925-954. 
  7. ^ "US-FDA Fluvoxamine Product Insert" (March 2005). 
  8. ^ John T Walker MD, Michael J. Labelarte MD et.al. (April 26, 2001). "Fluvoxamine for the treatment of anxiety disorders in children and adolescents". The New England Journal of Medicine 344: 1279-1285. 
  9. ^ Emmanuel, et al. (1997). "Treatment of Irritable Bowel Syndrome with Fluvoxamine". Am J Psychiatry 154: 711-712. 
  10. ^ J., Hyttel (1993). "Comparative pharmacology of selective serotonin reuptake inhibitors (SSRIs)". Nordisk Journal of Psychiatric 47 (Suppl 30): 5-12. 
  11. ^ Hashimoto K et al., Narita N (1996). "Interactions of selective reuptake inhibitors with subtypes of sigma receptor in rat brain". Eur J Pharmacol 307: 117-9. 
  12. ^ C.Sandner, Carrasco JL (December 2005). "Clinical effects of pharmacological variations in selective serotonin reuptake inhibitors: an overview". International Journal of Clinical Practice 59 (12): 1428-1434. 
  13. ^ P., Baumann (1996). "Pharmacokinetic-pharmacodynamic relationship of the Selective serotonin reuptake inhibitors". Clinical Pharmacokinetics 31: 444-469. 
  14. ^ Gill HS, DeVane CL (1997). "Clinical Pharmacokinetics of Fluvoxamine: applications to dosage regime design". Journal of Clinical Psychiatric 58 (Suppl 5): 7-14. 
  15. ^ DeVane, CL (1998). "Translational pharmacokinetics: current issues with newer antidepressants". Depression and Anxiety 8 (Suppl 1): 64-70. 
  16. ^ Kroom, Lisa A. (10-01-2007). "Drug Interactions With Smoking". Am J Health-Syst Pharm. 64 (18): 1917-1921. Medscape: American Society of Health-System Pharmacists. 
  17. ^ Waknine, Yael (April 13, 2007). Prescribers Warned of Tizanidine Drug Interactions. Medscape News. Medscape. Retrieved on 2008-02-01.
  18. ^ Bondy, Brigitta; Illja Spellmann (2007). "Pharmacogenetics of Antipsychotics: Useful For the Clinician?". Curr Opin Psychiatry 20 (1): 126-130. Medscape: Lippincott Williams & Wilkins. 
  19. ^ Hengeveld VW et al., Waldinger MD (1998). "Effect of SSRI antidepressants on ejaculation: a double blind, randomised, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline". Journal of Clinical Psychopharmacology 18: 274-281. 
  20. ^ Riley, A.; R.T. Segraves (2006). "Treatment of Premature Ejaculation". Int J. Clin Pract. 60 (6): 694-697. Blackwell Publishing. 

[edit] External links

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