|Systematic (IUPAC) name|
|Trade names||Luvox, Floxyfral, Fevarin|
|Legal status||Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)|
|Bioavailability||53% (90% confidence interval: 44-62%)|
|Metabolism||Hepatic (via cytochrome P450 enzymes. Mostly via oxidative demethylation)|
|Half-life||12-13 hours (single dose), 22 hours (repeated dosing)|
|Excretion||Renal (98%; 94% as metabolites, 4% as unchanged drug)|
|(what is this?)|
Fluvoxamine (brand names: Floxyfral, Luvox, Fevarin) 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 posttraumatic 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. A study from the Institute for Safe Medication Practices identified reports of violence from those taking fluvoxamine as being 8.4 times higher than expected given the volume of overall reports for that drug. (Five reports of violence.)
Fluvoxamine's only FDA approved indication is in the treatment of obsessive-compulsive disorder (OCD), although in other countries (e.g. Australia and the UK) it has indications for major depressive disorder as well. Fluvoxamine has been found to be useful in the treatment of major depressive disorder (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, with research showing that fluvoxamine 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.
There is some evidence that 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.
Fluvoxamine shares a number of adverse effects with other SSRIs. These side effects include the following: Gastrointestinal side effects are more common in those receiving fluvoxamine than with other SSRIs.
- Common (1-10% incidence) adverse effects
- Anorexia (weight loss)
- Tachycardia (high heart rate)
- Abdominal pain
- Dyspepsia (indgestion)
- Dry mouth
- Hyperhidrosis (excess sweating)
- Asthenia (weakness)
- Sexual dysfunction (including delayed ejaculation, erectile dysfunction, decreased libido, etc.)
- Uncommon (0.1-1% incidence) adverse effects
- Confusional state
- Extrapyramidal side effects (e.g. dystonia, parkinsonism, tremor, etc.)
- Orthostatic hypotension
- Cutaneous hypersensitivity reactions (e.g. oedema [build up of fluid in the tissues], rash, pruritus)
- Rare (0.01-0.1% incidence) adverse effects
- Abnormal hepatic (liver) function
- Photosensitivity (being abnormally sensitive to light)
- Galactorrhoea (expulsion of breast milk that's 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
- Urinary incontinence
- Urinary retention
- 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.), 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
- Withdrawal symptoms
- Weight changes
- Suicidal ideation & behaviour
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- CYP1A2 (strongly) which metabolises agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine, etc.
- CYP3A4 (weakly) which metabolises aripiprazole, clozapine, haloperidol, quetiapine, ziprasidone, etc.
- CYP2D6 (weakly) which metabolises aripiprazole, chlorpromazine, clozapine, codeine, fluoxetine, haloperidol, olanzapine, oxycodone, paroxetine, perphenazine, pethidine, risperidone, sertraline, thioridazine, zuclopenthixol, etc.
- CYP2C9 (moderately) which metabolises Non-steroidal anti-inflammatory drugs, phenytoin, sulfonylureas, etc.
- CYP2C19 (strongly) which metabolises diazepam, phenytoin, etc.
- CYP2B6 (weakly) which metabolises bupropion, cyclophosphamide, sertraline, tamoxifen, valproate, etc.
by so doing fluvoxamine can increase serum concentration of the substrates of the aforementioned enzymes.
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 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.
Fluvoxamine was developed by Kali-Duphar, part of Solvay Pharmaceuticals, Belgium, now Abbott Laboratories, and introduced as Floxyfral in Switzerland in 1983 and Solvay in West Germany in the same year. 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 to patients with major depression in many countries. It was the first SSRI, a non-TCA drug, approved by the U.S. Food and Drug Administration 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.
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 after switching from sertraline (Zoloft). 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 to the U.S. market, which is now manufactured by Palo Alto, California-based Jazz Pharmaceuticals, Inc. On February 28, 2008, the FDA approved a controlled-release formulation of fluvoxamine for Solvay Pharmaceuticals, to be marketed as Luvox CR.
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