FLUVOXAMINE MALEATE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity by blocking the reuptake of serotonin at the presynaptic neuronal membrane, thereby increasing serotonin concentrations in the synaptic cleft. It also has sigma-1 receptor agonism, which may contribute to its antidepressant and anxiolytic effects.
| Metabolism | Fluvoxamine is extensively metabolized in the liver, primarily via oxidative demethylation and deamination. The major metabolic enzyme is CYP2D6, with minor contributions from CYP1A2 and CYP3A4. It is a potent inhibitor of CYP1A2 and CYP2C19, and a moderate inhibitor of CYP2C9, CYP2D6, and CYP3A4. |
| Excretion | Renal: 90-98% (as metabolites, <2.5% unchanged), Fecal: 2-10% |
| Half-life | Terminal half-life: 15.6 hours (range 13-20 hours) after single dose, slightly prolonged in elderly and hepatic impairment; steady-state achieved after 7-10 days. |
| Protein binding | ~80% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Vd: ~25 L/kg (range 20-30 L/kg), indicating extensive tissue distribution including CNS. |
| Bioavailability | Oral: ~53% (due to first-pass metabolism). |
| Onset of Action | Oral: Clinical improvement in obsessive-compulsive and depressive symptoms typically begins within 1-2 weeks; full therapeutic effect may require 4-8 weeks. |
| Duration of Action | Oral: Duration of action correlates with half-life; plasma levels remain above minimal effective concentration for approximately 24 hours with once-daily dosing. Steady-state maintained with regular administration. |
50-100 mg orally once daily at bedtime, may increase by 50 mg every 4-7 days; maximum 300 mg/day. Effective total daily dose range: 100-200 mg.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <10 mL/min) due to lack of data. |
| Liver impairment | Child-Pugh Class A: 25-50 mg once daily. Child-Pugh Class B: 25 mg once daily. Child-Pugh Class C: Use not recommended; if necessary, administer with extreme caution, maximum 50 mg/day. |
| Pediatric use | Children (8-17 years): Start 25 mg once daily at bedtime; increase by 25 mg every 4-7 days as tolerated. Usual dose: 50-200 mg/day. Maximum 300 mg/day (lower end for younger children). Weight-based: insufficient data; total daily dose not to exceed 8-10 mg/kg. |
| Geriatric use | Start 25 mg once daily at bedtime; increase slowly (by 25 mg every 7 days). Usual therapeutic dose: 100-200 mg/day. Maximum 300 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong inhibitor of CYP1A2 and CYP2C19 affecting many drugs (eg theophylline clozapine) May increase risk of bleeding especially with NSAIDs or warfarin.
| Breastfeeding | Fluvoxamine is excreted into breast milk; M/P ratio approximately 0.29. Levels are low to undetectable in infant plasma. Cases of irritability, poor feeding, and drowsiness reported rarely. Benefits may outweigh risks; monitor infant for sedation and feeding issues. |
| Teratogenic Risk | First trimester: SSRI use associated with small increased risk of congenital cardiac malformations (RR ~1.5-2.0). Second/third trimester: Risk of persistent pulmonary hypertension of the newborn (PPHN) (OR ~2.0), poor neonatal adaptation syndrome (PNAS) including respiratory distress, feeding difficulties, irritability, and tremors. Late third trimester exposure may increase risk of postpartum hemorrhage due to platelet dysfunction. |
■ FDA Black Box Warning
Fluvoxamine carries a black box warning for increased risk of suicidal thinking and behavior in children, adolescents, and young adults (age 24 and younger) with major depressive disorder and other psychiatric disorders. Patients should be closely monitored for clinical worsening, suicidality, or unusual changes in behavior.
| Common Effects | Nausea |
| Serious Effects |
["Concomitant use with MAOIs (monoamine oxidase inhibitors) or within 14 days of MAOI therapy due to risk of serotonin syndrome.","Concomitant use with linezolid or intravenous methylene blue.","Hypersensitivity to fluvoxamine or any component of the formulation.","Concurrent use with pimozide or thioridazine (due to inhibition of their metabolism and risk of QT prolongation).","Co-administration with ramelteon (fluvoxamine inhibits CYP1A2, increasing ramelteon levels)."]
| Precautions | ["Serotonin syndrome: Risk when used with other serotonergic drugs (e.g., MAOIs, triptans, other SSRIs, linezolid).","Suicidality: Monitor for worsening depression or suicidal ideation.","QT prolongation: May prolong QT interval; use caution in patients with risk factors (e.g., electrolyte disturbances, concomitant QT-prolonging drugs).","Hyponatremia: Risk of syndrome of inappropriate antidiuretic hormone secretion (SIADH).","Bleeding risk: May increase risk of bleeding, especially with NSAIDs, aspirin, or anticoagulants.","Activation of mania/hypomania: Caution in patients with bipolar disorder.","Seizures: Use with caution in patients with seizure disorders.","Sexual dysfunction: May cause ejaculatory delay or anorgasmia."] |
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| Fetal Monitoring | Baseline and periodic liver function tests, renal function. Monitor mood and suicidality. Fetal ultrasound for anatomy if first trimester exposure. Assessment for signs of PNAS at birth. Monitor for postpartum hemorrhage. |
| Fertility Effects | May cause reversible reductions in sperm count and motility in males. No clear evidence of impaired female fertility; however, hyperprolactinemia can occur, potentially affecting ovulation. Overall, effect on fertility is minimal and reversible. |