SSRI — also a strong CYP1A2 inhibitor (raises clozapine, theophylline, melatonin, caffeine to clinically meaningful degrees). FDA-approved for OCD; off-label for depression + early COVID-19 (the "TOGETHER" trial).
Half-Life (t½)
PO: 16h
Dosing Guidelines
PO: Typical 100 mg (Range: 50–300 mg)
Target Organ Systems
nervous
endocrine
digestive
Interactions
Caffeine (major): Strong CYP1A2 inhibition. Jeppesen 1996 (PMID:8807660): fluvoxamine 100 mg/d × 8 d dropped caffeine total CL from 107 to 21 mL/min (5.1× reduction); t½ rose 5 to 31 h. Restrict caffeine on fluvoxamine to avoid jitteriness / insomnia.
Melatonin (major): CYP1A2 inhibition. Härtter 2000 (PMID:10668847) n=5 healthy males, single 5 mg melatonin PO ± 50 mg fluvoxamine: melatonin AUC 17× higher (P<.05), Cmax 12× higher (P<.01). Ki ≈ 0.16/(17−1) = 0.010 µM (Cp_perp ~0.16 µM at 100 mg/d). Endogenous melatonin similarly elevated at night → daytime drowsiness; avoid co-administration.
Olanzapine (warn): CYP1A2 inhibition. Chiu 2004 (PMID:15545309) n=10 male schizophrenia smokers, fluvoxamine 50→100 mg/d × 4 wk: olanzapine AUC up 30–55%, Cmax 12–64%, t½ 25–32%; Vd −4 to −26%, CL −26 to −38%. Smoker cohort = induced CYP1A2 baseline mutes magnitude vs nonsmokers. Ki ≈ 0.16/(1.55−1) = 0.29 µM. TDM-driven dose adjustment.
Duloxetine (major): CYP1A2 inhibition. Lobo 2008 (PMID:18307373) clinical PK study: oral duloxetine 60 mg ± steady-state fluvoxamine 100 mg/d → duloxetine AUC ↑460% (90% CI 359, 584), Cmax ↑141%; oral F rose 42.8% → 81.9%. Ki ≈ 0.16/(5.6−1) = 0.035 µM. FDA label warns against the combination.
Ramelteon (contraindicated): CYP1A2 inhibition (extreme). Obach 2010 (PMID:20478852) reports the in vivo ramelteon-fluvoxamine DDI verbatim as "128-fold actual" exposure increase (Rozerem-label data). Iga 2015 (PMID:26099559) corroborates "130-fold". Ki ≈ 0.16/(128−1) = 0.0013 µM. Rozerem prescribing information explicitly contraindicates concomitant use; first-pass CYP1A2 inhibition essentially abolishes ramelteon clearance.
Tizanidine (contraindicated): CYP1A2 inhibition. Granfors 2004 (PMID:15060511) n=10 healthy, fluvoxamine 100 mg/d × 4 d then 4 mg tizanidine: AUC 33× (range 14–103×, P=2e-6), Cmax 12× (range 5–32×), t½ 1.5→4.3 h. Severe hypotension to 80 mmHg systolic. Ki ≈ 0.16/(33−1) = 0.005 µM. Authors: "concomitant use of tizanidine with fluvoxamine, or other potent inhibitors of CYP1A2, should be avoided."
Clozapine (caution): CYP1A2 inhibition (strong). Diaz 2008 (PMID:18484549) verbatim: "fluvoxamine (E=+263%) and paroxetine (E=+30%) inhibit it [clozapine metabolism]". Mixed-model analysis of 255 patients, 415 SS troughs, controlling for smoking + valproate. Css ratio 1+2.63 = 3.63×; Ki ≈ 0.16/2.63 = 0.061 µM. Naturalistic data — less precise than a controlled crossover but reflects real-world clozapine + SSRI co-prescription practice.
Tacrine (major): CYP1A2 inhibition (strong). Becquemont 1997 (PMID:9209244) verbatim: tacrine AUC "27 (95% CI, 19 to 38) ng.hr/ml versus 224 (95% CI, 166 to 302) ng.hr/ml". 13 healthy volunteers, double-blind randomized crossover, fluvoxamine 100 mg/d × 6d + single 40 mg PO tacrine. AUC ratio 224/27 = 8.30×; apparent oral CL 1683 → 200 L/hr (88% reduction). Ki ≈ 0.16/7.30 = 0.022 µM. Tacrine withdrawn 2013 — retained as textbook CYP1A2 reference data.