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Fluvoxamine
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Fluvoxamine (Luvox) is an antidepressant which functions as a selective serotonin reuptake inhibitor. It is most often used to treat obsessive-compulsive disorder.
oxamine 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.
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Encyclopedia
Fluvoxamine (Luvox) is an antidepressant which functions as a selective serotonin reuptake inhibitor. It is most often used to treat obsessive-compulsive disorder.
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. 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. 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. A generic version of Luvox is available from IVAX Pharmaceuticals, Inc.
Fluvoxamine was the first SSRI to be registered for the treatment of Obsessive Compulsive Disorder in children by FDA in 1997.
Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.
On February 28, 2008, the US FDA approved a controlled-release formulation of fluvoxamine, to be marketed as Luvox CR.
Indications
Fluvoxamine is widely prescribed to treat major depression, and anxiety disorders such as Obsessive-Compulsive Disorder, Obsessive-Compulsive Spectrum Disorder, Panic Disorder, Social Phobia, and Post-Traumatic Stress Disorder.
Fluvoxamine is indicated for children and adolescents with OCD.
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.
Fluvoxamine may help in the treatment of Irritable Bowel Syndrome.
Adverse 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 are quite rare side effects with fluvoxamine, contrary to other SSRIs.
Pharmacology
Fluvoxamine is one of the few SSRIs to have a monocyclic structure.
Although all SSRIs inhibit the reuptake of serotonin, the pharmacological and adverse effect profiles of fluvoxamine are different from those of other drugs in its class.
Among the SSRIs, fluvoxamine has the highest affinity for sigma receptor subtype 1 (s1receptors), 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).
Pharmacokinetics
Absorption
The oral absorption of fluvoxamine is equal to or more than 94%.
Distribution
The plasma protein binding is only about 76%.
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.
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.
Elimination
Fluvoxamine has the shortest half-life of all the SSRIs. Its mean serum half-life is 15.6 hours, at steady state, with multiple 100 mg/day oral doses.
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.
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, 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. A recent warning has been published regarding potentially serious interaction with Tizanidine, based on CYP1A2 metabolism.
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.
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: CYP3A4, CYP2C9, and CYP2C19
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