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Fluvoxamine

Fluvoxamine, sold under the brand name Luvox, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.

It is primarily used to treat major depressive disorder and obsessive–compulsive disorder (OCD.

6] but is also used to treat anxiety disorders such as panic disorder, social anxiety disorder, and post-traumatic stress disorder.

Pregnancy category AU: C

Routes of administration-By mouth

Drug class-Selective serotonin reuptake inhibitor (SSRI)

Bioavailability 53% 

Protein binding 77–80%

Metabolism

Liver by cytochrome P450 enzymes. Mostly via oxidative demethylation.

Elimination half-life 12–13 hours for single dose, 22 hours for repeated dosing.

Excretion:

Kidney (98%

94% as metabolites, 4% as unchanged drug

Fluvoxamine’s side-effect profile is very similar to other SSRIs: 

constipation, gastrointestinal problems, headache, anxiety, irritation, sexual problems, dry mouth, sleep problems and a risk of suicide at the start of treatment by lifting the psychomotor inhibition, but these effects appear to be significantly weaker than with other SSRIs except for gastrointestinal side-effects.

The tolerance profile is superior with respect to cardiovascular complications.

It also approved in the United States for obsessive–compulsive disorder, depression and social anxiety disorder.

It is indicated for children and adolescents with OCD.

The drug possess some analgesic properties in line with other SSRIs and tricyclic antidepressants.

It may help some people with negative symptoms of chronic schizophrenia.

Fluvoxamine is effective for social phobia in adults.

Fluvoxamine is effective for treating a range of anxiety disorders in children and adolescents, including generalized anxiety disorder, social anxiety disorder, panic disorder and separation anxiety disorder.

Its side-effect profile is very similar to other SSRIs.

Common (1–10% incidence) adverse effects;

Abdominal pain

Agitation

Anxiety

Asthenia 

Constipation

Diarrhea

Dizziness

Dyspepsia 

Headache

Hyperhidrosis 

Insomnia

Loss of appetite

Malaise

Nausea

Nervousness

Palpitations

Restlessness

Sexual dysfunction 

Somnolence 

Tachycardia 

Tremor

Vomiting

Weight loss

Xerostomia 

Yawning

Uncommon (0.1–1% incidence) adverse effects

Arthralgia

Confusional state

Cutaneous hypersensitivity reactions

Extrapyramidal side effects 

Hallucination

Orthostatic hypotension

Rare (0.01–0.1% incidence) adverse effects

Abnormal hepatic function

Galactorrhoea 

Mania

Photosensitivity 

Seizures

Other infrequent adverse effects

Akathisia 

Bed-wetting

Bone fractures

Dysgeusia

Ecchymoses

Glaucoma

Hyperprolactinaemia-galactorrhoea, amenorrhea 

Hyponatremia 

Mydriasis

Neuroleptic malignant syndrome

Paraesthesia

Serotonin syndrome 

Suicidal ideation and behavior

Syndrome of inappropriate antidiuretic hormone secretion

Urinary incontinence

Urinary retention

Violence 

Weight changes

Withdrawal symptoms

Luvox (fluvoxamine) 100 mg film-coated scored tablets

Fluvoxamine inhibits cytochrome P450 enzymes: 

CYP1A2 which metabolizes agomelatine, amitriptyline, caffeine, clomipramine, clozapine, duloxetine, haloperidol, imipramine, phenacetin, tacrine, tamoxifen, theophylline, olanzapine.

CYP3A4 which metabolizes alprazolam, aripiprazole, clozapine, haloperidol, quetiapine, pimozide, ziprasidone.

CYP2D6 metabolizes aripiprazole, chlorpromazine, clozapine, codeine, fluoxetine, haloperidol, olanzapine, oxycodone, paroxetine, perphenazine, pethidine, risperidone, sertraline, thioridazine, zuclopenthixol.

CYP2C9 which metabolizes nonsteroidal anti-inflammatory drugs, phenytoin, sulfonylureas.

CYP2C19 metabolizes clonazepam, diazepam, phenytoin.

CYP2B6 metabolizes bupropion, cyclophosphamide, sertraline, tamoxifen, valproate.

Fluvoxamine can therefore increase serum concentration of the substrates of these enzymes.

Fluvoxamine may also elevate plasma levels of olanzapine by approximately two times.

The plasma levels of oxidatively metabolized benzodiazepines: triazolam, midazolam, alprazolam and diazepam are likely to be increased when co-administered with fluvoxamine. 

Clearance of benzodiazepines metabolized by glucuronidation: lorazepam, oxazepam, temazepam are unlikely to be affected by fluvoxamine, as are benzodiazepines metabolized by nitro-reduction: clonazepam, nitrazepam .

If alprazolam is coadministered with fluvoxamine, the initial alprazolam dose should be reduced to the lowest effective dose.

Fluvoxamine has been observed to increase serum concentrations of mirtazapine, by three- to four-fold in humans, therefore adjustment of dosage as necessary are warranted when combining fluvoxamine and mirtazapine.

Because of the potentially hazardous consequences, the concomitant use of tizanidine with fluvoxamine, or other potent inhibitors of CYP1A2, should be avoided.

It is a potent 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 site.

It is a potent agonist at the serotonin transporter receptor and has the highest affinity (36 nM) of any SSRI for doing so. contributing to its antidepressant and anxiolytic effects and may also afford it some efficacy in treating the cognitive symptoms of depression.

Fluvoxamine’s metabolites are pharmacologically neutral.

It is prescribed in many countries to patients with major depression.

It was the first SSRI, a non-TCA drug, approved by the U.S. FDA specifically for the treatment of OCD.

There is tentative evidence fluvoxamine might be useful for reducing COVID-19 disease severity if given as an early treatment.

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