fluvoxamine (Luvox)
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Introduction
Tradename: Luvox.
Indications
- depression
- post traumatic stress disorder (PTSD)
- obsessive compulsive disorder (OCD)
- self-injurious behavior
- mania[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:
- use with caution in patients with history of seizures
- may cause mania or hypomania in patients with depression or bipolar disorder
Dosage
- start 50 mg PO QHS, max 300 mg/day
- doses > 100 mg/day should be given BID
- optimal dose for major depression is 100 mg QD[7]
- Covid-19: 100 mg BID for 10 days[10]
Tabs: 50 & 100 mg.
Pharmacokinetics
- well absorbed orally, not affected by food
- metabolized by liver to more than 30 inactive metabolites
- 1/2life is 16 hours, increased to 26 hours in the elderly
- allow 3-6 weeks for full therapeutic effect
elimination via liver
1/2life = 13-90 hours
protein binding = >67 %
elimination by hemodialysis = -
Adverse effects
- common (> 10%)
- 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
- uncommon (< 1%)
- other
- increased sweating
- drowsiness
- causes less anxiety, agitation & insomnia than fluoxetine
- SIADH & hyponatremia[5]
- drug adverse effects of SSRIs
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- fluvoxamine decreases central hypotensive effects of clonidine
- MAO inhibitors incombination may cause hypertension, tachycardia, seizures, death - do NOT administer within 2 weeks of each other
- selegiline in combination increases the risk of serotonin syndrome
- 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
- fluvoxamine inhibits metabolism of:
- warfarin
- theophylline
- metoprolol, propranolol & possibly other beta-blockers
- fluvoxamine increases effect/toxicity of:
- tricyclic antidepressants (TCA)
- benzodiazepines
- clozapine
- methadone & possibly other opiates
- carbamazepine
- diltiazem
- increased effect/toxicity with tryptophan, Li+
- QT prolongation with:
- may be interaction with phenytoin
- drug interaction(s) of oral anticoagulants with selective serotonin reuptake inhibitor (SSRI)
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of ondanstetron with SSRIs
- drug interaction(s) of dextromethorphan with SSRIs
- drug interaction(s) of trazodone with SSRIs
- drug interaction(s) of tramadol with SSRIs
- drug interaction(s) of triptans with SSRIs
- drug interaction(s) of anti-platelet agents with SSRIs
- drug interaction(s) of methylene blue with SSRIs
- drug interaction(s) of linezolid with SSRIs
- drug interaction(s) of statins with SSRIs
- drug interaction(s) of hypericum perforatum (Sr John's wort) with SSRI
- drug interaction(s) of tamoxifen with SSRI
- drug interaction(s) of theophylline with fluvoxamine
- drug interaction(s) of tizanidine with fluvoxamine
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with SSRIs
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of antidepressant with opiates
- drug interaction(s) of coxib with SSRI
Laboratory
- specimen:
- methods: HPLC, TLC, GC
- interferences:
- imipramine may interfere with HPLC assay
Mechanism of action
- selective serotonin reuptake inhibitor (SSRI)
- potent cyt P450 1A2 inhibitor
- 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]
More general terms
Additional terms
- 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)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 5.0 5.1 Prescriber's Letter 9(7):38 2002
- ↑ 6.0 6.1 Deprecated Reference
- ↑ 7.0 7.1 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; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26552940 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
- ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/33180097 https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.22760 - ↑ 9.0 9.1 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 - ↑ 10.0 10.1 10.2 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: https://www.ncbi.nlm.nih.gov/pubmed/34717820 PMCID: PMC8550952 Free PMC article https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext - ↑ 11.0 11.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36633838 https://jamanetwork.com/journals/jama/fullarticle/2800448