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fluvoxamine (Luvox)

Tradename: Luvox. Indications: 1) depression 2) post traumatic stress disorder (PTSD) 3) obsessive compulsive disorder (OCD) 4) self-injurious behavior 5) mania [6] 6) investigational use for Covid-19 - may reduce risk of clinical deterioration in adult outpatients with symptomatic COVID-19 [8] (RR=0.7, see Clinical trials below) - TOGETHER trial from Brazil may provide similar or better results (see Clinical trials below) Contraindications: - use of MAO inhibitor within 14 days Caution: 1) use with caution in patients with history of seizures 2) may cause mania or hypomania in patients with depression or bipolar disorder Dosage: 1) start 50 mg PO QHS, max 300 mg/day 2) doses > 100 mg/day should be given BID 3) optimal dose for major depression is 100 mg QD [7] 4) Covid-19: 100 mg BID for 10 days [10] Tabs: 50 & 100 mg. Pharmacokinetics: 1) well absorbed orally, not affected by food 2) metabolized by liver to more than 30 inactive metabolites 3) 1/2life is 16 hours, increased to 26 hours in the elderly 4) allow 3-6 weeks for full therapeutic effect Adverse effects: 1) common (> 10%) - nausea 2) less common (1-10%) - palpitations, somnolence, headache, insomnia, dizziness, nervousness, mania, hypomania, vertigo, thought disorder, agitation, anxiety, malaise, amnesia, impotence, xerostomia, abdominal pain, vomiting, dyspepsia, constipation, diarrhea, abnormal taste, anorexia, tremors, weakness, diaphoresis 3) uncommon (< 1%) - seizures, toxic epidermal necrolysis, thrombocytopenia, hepatic dysfunction, increased serum creatinine, extrapyramidal symptoms 4) other a) increased sweating b) drowsiness c) causes less anxiety, agitation & insomnia than fluoxetine d) SIADH & hyponatremia [5] Drug interactions: 1) fluvoxamine decreases central hypotensive effects of clonidine 2) MAO inhibitors incombination may cause hypertension, tachycardia, seizures, death - do NOT administer within 2 weeks of each other 3) selegiline in combination increases the risk of serotonin syndrome 4) fluvoxamine strongly inhibits cyt P450 1A2 & moderately inhibits cyt P450 2C9 & cyt P450 3A4, thus may increase levels of drugs metabolized by these cyt P450's 5) fluvoxamine inhibits metabolism of: a) warfarin b) theophylline c) metoprolol, propranolol & possibly other beta-blockers 6) fluvoxamine increases effect/toxicity of: a) tricyclic antidepressants (TCA) b) benzodiazepines c) clozapine d) methadone & possibly other opiates e) carbamazepine f) diltiazem 7) increased effect/toxicity with tryptophan, Li+ 8) QT prolongation with: - terfenadine, cisapride, astemizole 9) may be interaction with phenytoin Laboratory: 1) specimen: a) plasma (heparin) b) stable for 6 months at -20 degrees C 2) methods: HPLC, TLC, GC 3) interferences: -> imipramine may interfere with HPLC assay Mechanism of action: 1) selective serotonin reuptake inhibitor (SSRI) 2) potent cyt P450 1A2 inhibitor 3) lipophilic sigma-1 receptor agonist Clinical trials: - a 10-day course of fluvoxamine cut emergency department & hospital admissions by 29% [9] - TOGETHER trial from Brazil [10] - fluvoxamine reduces composite of observation in a COVID-19 emergency setting for >6 hours or transfer to a tertiary hospital (RR=0.68) - intention-to-treat analysis (17 vs 25 deaths, RR=0.68) - no significant differences in: - viral clearance at day 7 - hospitalizations due to COVID - all-cause admissions - time to hospitalization - duration of hospital stay - number of days on mechanical ventilation - time to recovery - 50 mg of fluvoxamine twice daily for 10 days does not improve time to recovery vs placebo [11]

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2) cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

General

amine selective serotonin reuptake inhibitor (SSRI)

Properties

MISC-INFO: elimination route LIVER 1/2life 13-90 HOURS protein-binding >67% elimination by hemodialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  5. Prescriber's Letter 9(7):38 2002
  6. Deprecated Reference
  7. Jakubovski E et al. Systematic review and meta-analysis: Dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry 2015 Nov 10; PMID: 26552940 http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
  8. Brooks M Antidepressant Shows Early Promise for Mild COVID-19 Medscape - Nov 19, 2020 https://www.medscape.com/viewarticle/941292 - Lenze EJ, Mattar C, Zorumski CF et al Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19A Randomized Clinical Trial. JAMA. Published online November 12, 2020. PMID: 33180097 https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.22760
  9. Landhuis E Antidepressant Helps Prevent Hospitalization in COVID Patients: Study. Medscape August 27, 2021 https://www.medscape.com/viewarticle/957426 - Reis G, dos Santos Moreira Silva EA, Medeiros Silva DC et al Effect of Early Treatment with Fluvoxamine on Risk of Emergency Care and Hospitalization Among Patients with COVID-19: The TOGETHER Randomized Platform Clinical Trial. medRxiv August 23, 2021 https://www.medrxiv.org/content/10.1101/2021.08.19.21262323v1
  10. Landhuis E Antidepressant May Cut COVID-Related Hospitalization, Mortality: TOGETHER Published. Medscape. October 28, 2021 https://www.medscape.com/viewarticle/961799 - Sidik SM Common antidepressant slashes risk of COVID death. Nature News. 2021, October 29. https://www.nature.com/articles/d41586-021-02988-4 - Phend C Antidepressant for Mild COVID-19 Prevents Admissions Effect in randomized trial "compares favorably" to more pricey drugs. https://www.medpagetoday.com/infectiousdisease/covid19/95284 - Reis G, Dos Santos Moreira-Silva EA, Silva DCM et al Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. The Lancet Global Health. October 27, 2021 PMID: 34717820 PMCID: PMC8550952 Free PMC article https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext
  11. McCarthy MW, Naggie S, Boulware DR et al Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19A Randomized Clinical Trial. JAMA. 2023;329(4):296-305. Jan 12 PMID: 36633838 https://jamanetwork.com/journals/jama/fullarticle/2800448