LUVOX (Fluvoxamine maleate 100 mg): clinical trial results in COVID-19 patients

LUVOX (Fluvoxamine): 

Fluvoxamine REDUCED HOSPITALIZATIONS BY 67% and decreased death by 91%, reported in patients who took and tolerated the fluvoxamine 100 mg twice daily for 10 days, per October 27 Lancet Global Health.

The trial was initiated on June 2, 2020, with the current protocol reporting randomization to fluvoxamine from Jan 20 to Aug 5, 2021, when the trial arms were stopped for superiority. 741 patients were allocated to fluvoxamine and 756 to placebo. 

Investigators monitored participants for 28 days after treatment. In the placebo group, 119 of 756 patients, or 15.7 percent, developed complications requiring hospitalization or more than six hours of emergency care. In comparison, 79 of 741, or 10.7 percent, of fluvoxamine-treated patients got that sick. 

In this trial taking fluvoxamine cut emergency visits and hospitalization by 32 percent

Fluvoxamine cut serious complications in patients who took at least 80 percent of their doses by 66 percent and reduced mortality by 91 percent. In the placebo group, 12 patients died, compared with one who received the drug.  

FDA Approved use: Obsessive-compulsive disorder

Adult dose for FDA approved indication: 

Obsessive-compulsive disorder

• (Immediate-release) Initial, 50 mg/day orally at bedtime; may increase by 50-mg increments every 4 to 7 days to MAX 300 mg/day; usual effective range, 100 to 300 mg/day; divide into 2 doses when total dose exceeds 100 mg/day (FDA dosage)
• Extended-release) Initial, 100 mg/day orally at bedtime; may increase by 50-mg increments every week to MAX 300 mg/day; usual effective range, 100 to 300 mg/day (FDA dosage) 

Contraindications

Concomitant use with tizanidine, alosetron, pimozide, thioridazine,  and ramelteon

Concomitant use of MAOIs, including linezolid or IV methylene blue, within 14 days of fluvoxamine discontinuation 

Side effects:

Common

• Dermatologic: Sweating (7% )
• Gastrointestinal: Diarrhea (11% to 18% ), Loss of appetite (7% to 13% ), Indigestion (8% to 10% ), Nausea (34% to 40% ), Xerostomia (10% to 14% )
• Neurologic: Asthenia (Immediate-release, 14%; extended-release, 26% ), Dizziness (11% to 12% ), Insomnia (Immediate-release, 21%; extended-release, 35% ), Somnolence (22% to 27% ), Tremor (5% to 6% )
• Psychiatric: Anxiety (5% to 6% ), Feeling nervous (12% )
• Reproductive: Abnormal ejaculation (8% to 10% ), Orgasm incapacity (2% to 5% )

Serious

• Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis
• Endocrine metabolic: Hyponatremia
• Hematologic: Agranulocytosis, Hemorrhage, Abnormal
• Immunologic: Anaphylaxis
• Neurologic: Seizure (0.2% )
• Psychiatric: Depression, worsening, Suicidal thoughts, Suicide
• Other: Neuroleptic malignant syndrome, Serotonin syndrome

Pharmacology:

Fluvoxamine is known to stimulate Sigma-1 receptors and effectively reduce the secretion of cytokines, increased survival rates were found in two in vivo models of sepsis, LPS and fecal-induced peritonitis. (3)

References:

1. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext

2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022235lbl.pdf

3. https://www.authorea.com/users/337393/articles/462981-covid-19-cytokine-storm-and-sigma-1-receptors-potential-treatments-at-hand

4. https://molpharm.aspetjournals.org/content/89/1/142