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Fluvoxamine: Drug information

Fluvoxamine: Drug information
(For additional information see "Fluvoxamine: Patient drug information" and see "Fluvoxamine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidality and antidepressant drugs:

Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of fluvoxamine in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are associated with increases in the risk of suicide. Closely observe and appropriately monitor patients of all ages who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider. Fluvoxamine immediate release is not approved for use in pediatric patients, except for patients with obsessive-compulsive disorder (OCD). Fluvoxamine extended release (ER) has not been evaluated in pediatric patients.

Brand Names: Canada
  • ACT Fluvoxamine;
  • APO-Fluvoxamine;
  • Luvox;
  • RIVA-Fluvox [DSC];
  • SANDOZ Fluvoxamine [DSC]
Pharmacologic Category
  • Antidepressant, Selective Serotonin Reuptake Inhibitor
Dosing: Adult

Note: Initial dose and titration: In patients sensitive to side effects, some experts suggest a lower starting dose of 25 mg daily and gradual titration in increments of no more than 25 mg, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Craske 2021; Rausch 2001; Wylie 2000). Dosage forms: Fluvoxamine IR and ER formulations are interchangeable on a mg-to-mg basis. For the IR formulation, divide total daily doses >100 mg into twice-daily dosing.

Bulimia nervosa

Bulimia nervosa (off-label use): Oral: Immediate release: Initial: 50 mg once daily; increase dose based on response and tolerability up to 300 mg/day, dividing total daily doses >100 mg into twice-daily dosing (Brambilla 1995; Fichter 1996; Fichter 1997; Milano 2005).

Generalized anxiety disorder

Generalized anxiety disorder (off-label use):

Immediate release: Oral: Initial: 50 mg once daily; increase daily dose in 25 to 50 mg increments based on response and tolerability every ≥3 days up to a therapeutic dose of 100 mg/day; after 4 to 6 weeks, may continue increasing dose in 50 mg increments every 1 to 2 weeks up to a maximum dose of 300 mg/day. Divide total daily doses >100 mg/day into 2 divided doses (Craske 2021; Hirsch 2021; Rausch 2001; Wylie 2000).

Extended release: Oral: Use IR tablets to determine a stable daily dose and then convert to once daily extended release at same total daily dose.

Major depressive disorder

Major depressive disorder (off-label use): Oral: Immediate release: Initial: 50 mg once daily; increase dose based on response and tolerability to usual dosage range of 100 to 200 mg/day, dividing total daily doses >100 mg into twice-daily dosing; doses as high as 300 mg/day have been studied (Omori 2010; WFSBP [Bauer 2013]).

Obsessive-compulsive disorder

Obsessive-compulsive disorder:

Immediate release: Oral: Initial: 50 mg once daily at bedtime; may increase in 50 mg increments at 4- to 7-day intervals, as tolerated; usual dose range: 100 to 300 mg/day, dividing total daily doses >100 mg into twice-daily dosing; maximum dose: 300 mg/day.

Extended release: Oral: Initial: 100 mg once daily at bedtime; may increase in 50 mg increments at intervals of at least 1 week; usual dosage range: 100 to 300 mg/day; maximum dose: 300 mg/day

Panic disorder

Panic disorder (off-label use): Oral: Immediate release: Initial: 25 to 50 mg once daily; titrate gradually based on response and tolerability; usual dosage range: 100 to 200 mg/day, dividing total daily doses >100 mg into twice-daily dosing (APA 2009; Asnis 2001).

Post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) (off-label use): Oral: Immediate release: 75 mg twice daily (Spivak 2006).

Social anxiety disorder

Social anxiety disorder (off-label use): Oral:

Immediate release: Initial: 50 mg once daily; may increase in 50 mg increments at intervals of at least 1 week, dividing total daily doses >100 mg into twice-daily dosing; usual dosage range: 100 to 300 mg/day (Asakura 2007).

Extended release: Initial: 100 mg once daily at bedtime; may be increased in 50 mg increments at intervals of at least 1 week; usual dosage range: 100 to 300 mg daily; maximum dose: 300 mg/day (Davidson 2004; Stein 2003; Westenberg 2004)

Discontinuation of therapy:When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower taper (eg, over 4 weeks) include prior history of antidepressant withdrawal symptoms or high doses of antidepressants (APA 2010; Hirsch 2019). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from a monoamine oxidase inhibitor (MAOI). A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between 2 selective serotonin reuptake inhibitors), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Hirsch 2021; Ogle 2013; WFSBP [Bauer 2013]).

Switching to or from an MAOI:

Allow 14 days to elapse between discontinuing an MAOI and initiation of fluvoxamine.

Allow 14 days to elapse between discontinuing fluvoxamine and initiation of an MAOI.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling. Limited data suggest fluvoxamine does not accumulate in patients with renal impairment.

Dosing: Hepatic Impairment: Adult

Use lower initial doses and titrate slowly; use with caution. Some experts recommend a maximum dose of 150 mg in patients with moderate to severe hepatic impairment (Mauri 2014).

Dosing: Pediatric

(For additional information see "Fluvoxamine: Pediatric drug information")

Major depressive disorder

Major depressive disorder (unipolar): Limited data available:

Note: In the management of pediatric depression in adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, a selective serotonin reuptake inhibitor (SSRI) is recommended first line; fluvoxamine is not recommended first line due to the availability of 2 SSRIs with FDA approval for pediatric depression (fluoxetine, escitalopram) and the need for multiple doses a day. Fluvoxamine clinical trial evidence in adolescents is sparse; dosing based on expert recommendations (AAP [Cheung 2018]; APA 2019).

Adolescents: Immediate release: Oral: Initial: 25 to 50 mg once daily at bedtime; titrate in 50 mg increments (if initial daily dose 25 mg/day used, smaller titration increments may be necessary initially) at 1- to 2-week intervals; usual effective daily dose: 150 mg/day; maximum daily dose: 300 mg/day; daily doses >50 mg should be divided into 2 doses; if applicable, administer larger portion of daily dose at bedtime (AAP [Cheung 2018]; Cheung 2013; Mullen 2018).

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD):

Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary, it should be in combination with cognitive behavioral therapy (CBT) and an SSRI should be used first line; a preferred agent has not been identified (AACAP 2012, POTS Team 2004).

Immediate release:

Children 8 to 12 years: Note: Pharmacokinetic age-related and gender-related differences may affect doses at which therapeutic benefit is observed (see "Pharmacokinetics: Additional Considerations").

Oral: Initial: 12.5 to 25 mg once daily at bedtime; titrate in 25 mg increments at 7- to 14-day intervals to therapeutic effect; longer titration intervals may be necessary in some patients to minimize risk of behavior activation. Usual daily dosage range: 50 to 200 mg/day; daily doses >50 mg should be divided into 2 doses; if applicable, administer larger portion of daily dose at bedtime. Maximum daily dose: Children: 8 to 11 years: 200 mg/day; Children 12 years of age: 300 mg/day (AACAP 2012; Kotapati 2019; manufacturer's labeling).

Adolescents: Oral: Initial: 25 to 50 mg once daily at bedtime; titrate in 25 mg increments at 7- to 14-day intervals to therapeutic effect; longer titration intervals may be necessary in some patients to minimize risk of behavior activation. Usual daily dosage range: 50 to 200 mg/day; daily doses >50 mg should be divided into 2 doses; if applicable, administer larger portion of daily dose at bedtime. Maximum daily dose: Adolescents: 300 mg/day (AACAP 2012; Kotapati 2019; manufacturer's labeling).

Extended release: Limited data available: Children ≥8 years and Adolescents: Oral: Not for initial therapy; use the immediate-release formulation to initiate and titrate therapy; once patient is on a stable daily dose, convert to the extended-release formulation at same total daily dose and administer once daily if an appropriate mg-strength dosage form is available (manufacturer's labeling).

Discontinuation of therapy:

Consider planning discontinuation of therapy during lower-stress times, recognizing nonillness-related factors could cause stress or anxiety and be misattributed to treatment discontinuation (Hathaway 2018). Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks, with consideration given to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Fenske 2009; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Limited data suggest fluvoxamine does not accumulate in patients with renal impairment.

Dosing: Hepatic Impairment: Pediatric

Children ≥8 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling. Limited data suggest fluvoxamine clearance is reduced in patients with hepatic impairment. Some experts recommend a maximum daily dose of 150 mg/day in adult patients with moderate-severe hepatic impairment (Mauri 2014).

Dosing: Older Adult

Refer to adult dosing. Consider a lower initial dose; titrate slowly.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 24 Hour, Oral, as maleate:

Generic: 100 mg, 150 mg

Tablet, Oral, as maleate:

Generic: 25 mg, 50 mg, 100 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as maleate:

Luvox: 50 mg, 100 mg

Generic: 50 mg, 100 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Luvox CR capsule: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022033s011lbl.pdf#page=26

Fluvoxamine tablet: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021519s018lbl.pdf#page=31

Administration: Adult

Oral: May be administered with or without food. Do not crush, open, or chew ER capsules.

Bariatric surgery: Capsule, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER capsule cannot be opened. Consider switching to IR formulation, but dose adjustment may be necessary since the bioavailability of the IR formulation differs from the ER formulation.

Administration: Pediatric

Oral: May be administered without regard to meals. Do not chew or crush extended-release capsule; swallow whole.

Use: Labeled Indications

Obsessive-compulsive disorder: Treatment of obsessive-compulsive disorder (OCD) in pediatric patients 8 to 17 years of age and adults.

Use: Off-Label: Adult

Bulimia nervosa; Generalized anxiety disorder; Major depressive disorder; Panic disorder; Posttraumatic stress disorder; Social anxiety disorder

Medication Safety Issues
Sound-alike/look-alike issues:

FluvoxaMINE may be confused with flavoxATE, FLUoxetine, fluPHENAZine

Luvox may be confused with Lasix, Levoxyl, Lovenox

Older Adult: High-Risk Medication:

Beers Criteria: Selective Serotonin Reuptake Inhibitors (SSRIs) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2019]).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency varies by dosage form and indication. Adverse reactions reported as a composite of all indications.

>10%:

Central nervous system: Headache (22% to 35%), insomnia (21% to 35%), drowsiness (22% to 27%), dizziness (11% to 15%), nervousness (10% to 12%)

Gastrointestinal: Nausea (34% to 40%), diarrhea (11% to 18%), xerostomia (10% to 14%), anorexia (6% to 14%)

Genitourinary: Ejaculatory disorder (8% to 11%)

Neuromuscular & skeletal: Weakness (14% to 26%)

1% to 10%:

Cardiovascular: Chest pain (3%), palpitations (3%), vasodilation (2% to 3%), hypertension (1% to 2%), edema (≥1%), hypotension (≥1%), syncope (≥1%)

Central nervous system: Pain (10%), anxiety (5% to 8%), anorgasmia (2% to 5%), yawning (2% to 5%), abnormal dreams (3%), abnormality in thinking (3%), paresthesia (3%), agitation (2% to 3%), apathy (≥1% to 3%), central nervous system stimulation (2%), chills (2%), depression (2%), hypertonia (2%), psychoneurosis (2%), twitching (2%), amnesia (≥1%), manic reaction (≥1%), myoclonus (≥1%), psychotic reaction (≥1%), malaise (≤1%)

Dermatologic: Diaphoresis (6% to 7%), ecchymoses (4%), acne vulgaris (2%)

Endocrine & metabolic: Decreased libido (2% to 10%; incidence higher in males), hypermenorrhea (3%), weight loss (≥1% to 2%), weight gain (≥1%)

Gastrointestinal: Dyspepsia (8% to 10%), constipation (4% to 10%), vomiting (5% to 6%), abdominal pain (5%), flatulence (4%), dental caries (≤3%), tooth loss (≤3%), toothache (≤3%), dysgeusia (2% to 3%), dysphagia (2%), gingivitis (2%)

Genitourinary: Urinary frequency (3%), sexual disorder (2% to 3%), impotence (2%), urinary tract infection (2%), urinary retention (1%)

Hepatic: Abnormal hepatic function tests (2%)

Infection: Tooth abscess (≤3%), viral infection (2%)

Neuromuscular & skeletal: Tremor (5% to 8%), myalgia (5%), hyperkinesia (≥1%), hypokinesia (≥1%)

Ophthalmic: Amblyopia (2% to 3%)

Renal: Polyuria (2%)

Respiratory: Upper respiratory tract infection (9%), pharyngitis (6%), flu-like symptoms (3%), laryngitis (3%), bronchitis (2%), dyspnea (2%), epistaxis (2%), increased cough (≥1%), sinusitis (≥1%)

<1%, postmarketing, and/or case reports: Abnormal gait, activation syndrome, acute renal failure, aggressive behavior, agranulocytosis, akinesia, amenorrhea, anaphylaxis, anemia, angina pectoris, angioedema, angle-closure glaucoma, anuria, aplastic anemia, apnea, asthma, ataxia, blurred vision, bradycardia, bruxism, bullous skin disease, cardiac conduction delay, cardiomyopathy, cardiorespiratory arrest, cerebrovascular accident, cholecystitis, cholelithiasis, colitis, crying, decreased white blood cell count, delirium, diplopia, drowsiness (neonatal), dysarthria, dyskinesia, dystonia, extrapyramidal reaction, fatigue, fever, first degree atrioventricular block, gastroesophageal reflux disease, gastrointestinal hemorrhage, glossalgia, goiter, hallucination, hematemesis, hematuria, hemoptysis, hepatitis, homicidal ideation, hypercholesterolemia, hyperglycemia, hypersensitivity reaction, hypoglycemia, hypokalemia, hyponatremia, hypothyroidism, IgA vasculitis, impulsivity, interstitial pulmonary disease, intestinal obstruction, intoxicated feeling, irritability, jaundice, jitteriness, laryngismus, lethargy, leukocytosis, leukopenia, loss of consciousness, lymphadenopathy, melena, myasthenia, myocardial infarction, myopathy, neuroleptic malignant syndrome (Stevens 2008), outbursts of anger, pancreatitis, paralysis, Parkinsonian-like syndrome, pericarditis, porphyria, priapism, prolonged QT interval on ECG, purpura, Raynaud's phenomenon (Khouri 2016; Peiró 2007), renal insufficiency, rhabdomyolysis, seizure, serotonin syndrome, shock, SIADH, ST segment changes on ECG, Stevens-Johnson syndrome, suicidal tendencies, supraventricular extrasystole, tachycardia, tardive dyskinesia, thrombocytopenia, thromboembolism, toxic epidermal necrolysis, vasculitis, ventricular arrhythmia, ventricular tachycardia (including torsades de pointes)

Contraindications

Concurrent use with alosetron, pimozide, thioridazine, or tizanidine; use of MAO inhibitors intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either fluvoxamine or the MAO inhibitor); initiation of fluvoxamine in a patient receiving linezolid or intravenous methylene blue.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to fluvoxamine or any component of the formulation; concurrent use with astemizole, cisapride, mesoridazine, ramelteon, or terfenadine.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Fluvoxamine is FDA approved for the treatment of OCD in children ≥8 years of age.

- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression occur.

Concerns related to adverse effects:

• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).

• Impaired glucose control: Impaired glucose control (eg, hyperglycemia, hypoglycemia) has been reported; monitor for signs/symptoms of loss of glucose control particularly in diabetic patients.

• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Volume depletion and/or concurrent use of diuretics likely increases risk. Consider discontinuation if symptomatic hyponatremia occurs.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; fluvoxamine has not been systemically evaluated in patients with a recent history of MI or unstable heart disease.

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and half-life and plasma concentrations are increased; a lower dosage may be needed. However, selective serotonin reuptake inhibitors such as fluvoxamine are considered the safest antidepressants to use in chronic liver disease because of their relative lack of side effects and high therapeutic index (Mullish 2014).

• May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer may be effective for acute treatment of bipolar major depressive episodes, but should be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Fluvoxamine is not FDA approved for the treatment of bipolar depression.

• Seizure disorder: Use with caution in patients with a previous seizure disorder and avoid use with unstable seizure disorder. Discontinue use if seizures occur or if seizure frequency increases.

Concurrent drug therapy issues:

• Smokers: Fluvoxamine levels may be lower in patients who smoke.

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).

Warnings: Additional Pediatric Considerations

SSRI-associated behavioral activation (ie, restlessness, hyperkinesis, hyperactivity, agitation) is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults. Somnolence (including sedation and drowsiness) is more common in adults compared to children and adolescents (Safer 2006). May impair cognitive or motor performance. SSRI-associated vomiting is two- to threefold more prevalent in children compared to adolescents and is more prevalent in adolescents compared to adults (Safer 2006). A recent report (Lake 2000) describes five children (age 8 to 15 years) who developed epistaxis (n=4) or bruising (n=1) while receiving sertraline therapy. Another recent report describes the SSRI discontinuation syndrome in six children; the syndrome was similar to that reported in adults (Diler 2002). Due to limited long-term studies, the clinical usefulness of fluvoxamine should be periodically reevaluated in patients receiving the drug for extended intervals; effects of long-term use of fluvoxamine on pediatric growth, development, and maturation have not been directly assessed. Note: Case reports of decreased growth in children receiving fluoxetine or fluvoxamine (n=4; age: 11.6 to 13.7 years) for 6 months to 5 years suggest a suppression of growth hormone secretion during SSRI therapy (Weintrob 2002).

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2D6 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (strong), CYP2C19 (moderate), CYP2C9 (weak), CYP2D6 (weak), CYP3A4 (weak)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Acenocoumarol: FluvoxaMINE may increase the serum concentration of Acenocoumarol. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Agomelatine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Agomelatine. Risk X: Avoid combination

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification

Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Alosetron: FluvoxaMINE may decrease the metabolism of Alosetron. Risk X: Avoid combination

ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy

Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy

Anagrelide: CYP1A2 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Strong) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy

Asenapine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Asenapine. Risk C: Monitor therapy

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Astemizole: FluvoxaMINE may increase the serum concentration of Astemizole. Management: Avoid this combination when possible. The combination is specifically contraindicated in at least some non-US labeling. Risk D: Consider therapy modification

Belzutifan: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Belzutifan. Risk C: Monitor therapy

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bendamustine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Management: Consider alternatives to strong CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification

Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brivaracetam: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Brivaracetam. Risk C: Monitor therapy

Bromazepam: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination

BuPROPion: May enhance the adverse/toxic effect of FluvoxaMINE. Risk C: Monitor therapy

BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Carisoprodol: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Carisoprodol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Carisoprodol. Risk C: Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Cilostazol: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Cilostazol. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Reduce the cilostazol dose to 50 mg twice daily in patients who are also receiving moderate inhibitors of CYP2C19. Monitor clinical response to cilostazol closely. Risk D: Consider therapy modification

Cisapride: FluvoxaMINE may increase the serum concentration of Cisapride. Management: Avoid this combination when possible. The combination is specifically contraindicated in at least some non-US labeling. Risk X: Avoid combination

Citalopram: May enhance the antiplatelet effect of FluvoxaMINE. Citalopram may enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day. Monitor for signs and symptoms of bleeding, QTc prolongation, or serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor) if combined. Risk D: Consider therapy modification

CloBAZam: CYP2C19 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of CloBAZam. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of CloBAZam. Risk C: Monitor therapy

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

CloZAPine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Reduce the dose of clozapine to one-third of the original dose when adding a strong CYP1A2 inhibitor and monitor patient response closely. Return to the original clozapine dose when the strong CYP1A2 inhibitor is discontinued. Risk D: Consider therapy modification

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dexlansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Dexlansoprazole. Risk C: Monitor therapy

Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

DiazePAM: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of DiazePAM. Risk C: Monitor therapy

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

DULoxetine: May enhance the antiplatelet effect of FluvoxaMINE. DULoxetine may enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of DULoxetine. Risk X: Avoid combination

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Erlotinib: FluvoxaMINE may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Risk D: Consider therapy modification

Etizolam: FluvoxaMINE may increase the serum concentration of Etizolam. Risk C: Monitor therapy

Etravirine: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Etravirine. Risk C: Monitor therapy

Fenfluramine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP1A2 inhibitor. Risk D: Consider therapy modification

Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Flibanserin: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy

Gilteritinib: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor. Risk D: Consider therapy modification

Grapefruit Juice: May increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy

Haloperidol: FluvoxaMINE may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy

Lansoprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Lansoprazole. Risk C: Monitor therapy

Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification

Levobupivacaine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy

Levomethadone: May enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Levomethadone. Management: Monitor for increased methadone effects/toxicities if combined with fluvoxamine. Also monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if these agents are combined. Risk C: Monitor therapy

Lidocaine (Systemic): CYP1A2 Inhibitors (Strong) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification

Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Lumateperone: FluvoxaMINE may increase the serum concentration of Lumateperone. Risk C: Monitor therapy

Mavacamten: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Mavacamten. Risk X: Avoid combination

Melatonin: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Melatonin. Risk X: Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Methadone: May enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Methadone. Management: Monitor for increased methadone effects/toxicities if combined with fluvoxamine. Also monitor for signs and symptoms of serotonin syndrome/serotonin toxicity if these agents are combined. Risk C: Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Methysergide: FluvoxaMINE may increase the serum concentration of Methysergide. Risk X: Avoid combination

Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Mexiletine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Mexiletine. Risk C: Monitor therapy

Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy

Mivacurium: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

OLANZapine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of OLANZapine. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Omeprazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Omeprazole. Risk C: Monitor therapy

Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pentoxifylline: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy

Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Risk X: Avoid combination

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination

Pirfenidone: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and strong CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 801 mg per day (267 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider therapy modification

Pomalidomide: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pomalidomide. Management: Avoid when possible. If coadministration is necessary, reduce the pomalidomide dose to 2 mg and monitor for increased pomalidomide effects/toxicities. Risk D: Consider therapy modification

Proguanil: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Proguanil. CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Proguanil. Risk C: Monitor therapy

Propranolol: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Propranolol. Management: Use a lower initial propranolol dose and be more cautious during propranolol dose titration when combined with strong CYP1A2 inhibitors. Risk D: Consider therapy modification

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

QuiNIDine: FluvoxaMINE may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy

Ramelteon: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Risk X: Avoid combination

Ramosetron: May enhance the serotonergic effect of FluvoxaMINE. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Ramosetron. Management: Monitor for increased ramosetron effects/toxicities, including signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability) when these drugs are combined. Risk C: Monitor therapy

Rasagiline: FluvoxaMINE may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. FluvoxaMINE may increase the serum concentration of Rasagiline. Risk X: Avoid combination

Riluzole: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Riluzole. Risk C: Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy

Roflumilast-Containing Products: FluvoxaMINE may increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. FluvoxaMINE may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy

ROPINIRole: CYP1A2 Inhibitors (Strong) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy

Ropivacaine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Ropivacaine. Risk C: Monitor therapy

Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy

Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy

Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy

Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy

Talazoparib: May increase the serum concentration of FluvoxaMINE. Risk C: Monitor therapy

Tasimelteon: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Risk X: Avoid combination

Terfenadine: FluvoxaMINE may increase the serum concentration of Terfenadine. Management: Avoid this combination when possible. The combination is specifically contraindicated in at least some non-US labeling. Risk D: Consider therapy modification

Theophylline Derivatives: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, consider an empiric theophylline dose reduction to one-third of the original theophylline dose. Monitor for increased theophylline serum concentrations and toxicities when combined. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thioridazine: FluvoxaMINE may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of TiZANidine. Risk X: Avoid combination

Tobacco (Smoked): May decrease the serum concentration of FluvoxaMINE. Risk C: Monitor therapy

TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase the serum concentration of TOLBUTamide. Risk C: Monitor therapy

TraMADol: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Risk C: Monitor therapy

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy

Tricyclic Antidepressants: FluvoxaMINE may enhance the serotonergic effect of Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor therapy

Ubrogepant: FluvoxaMINE may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and consider avoiding a second dose for 24 hours when used with fluvoxamine. Risk D: Consider therapy modification

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Voriconazole: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Voriconazole. Risk C: Monitor therapy

Vortioxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Vortioxetine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Zolpidem: FluvoxaMINE may enhance the CNS depressant effect of Zolpidem. FluvoxaMINE may increase the serum concentration of Zolpidem. Risk C: Monitor therapy

Reproductive Considerations

Fluvoxamine is approved for the treatment of obsessive-compulsive disorder (OCD) and used off label for the treatment of unipolar major depressive disorder (WFSBP [Bauer 2013]). If treatment for OCD or major depressive disorder is initiated for the first time in patients planning to become pregnant, agents other than fluvoxamine are preferred (Larsen 2015).

Selective serotonin reuptake inhibitors (SSRIs) may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido has been reported in males and females; abnormal/delayed ejaculation and impotence have been reported in males with fluvoxamine use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with fluvoxamine is not known. SSRI-related sexual dysfunction may resolve with dose reduction or discontinuation of the SSRI; in some cases, sexual dysfunction may persist once therapy is discontinued (Coskuner 2018; Jing 2016; Waldinger 2015).

Pregnancy Considerations

Fluvoxamine crosses the human placenta (Newport 2003).

As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester exposure often have inconsistent results due to differences in study design and confounders such as maternal disease and social factors (Anderson 2020; Biffi 2020; Fitton 2020; Reefhuis 2015; Womersley 2017). Adverse effects in the newborn following SSRI exposure late in the third trimester can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required. Symptoms may be due to the toxicity of the SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn has been reported with SSRI exposure; although the absolute risk is small, monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). The long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are not known (CANMAT [MacQueen 2016]).

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of fluvoxamine may be altered. Based on limited data, maternal serum concentrations may be decreased in the third trimester. Close clinical monitoring as pregnancy progresses and therapeutic drug monitoring to detect patterns of changing plasma concentrations are recommended to assist dose adjustment when needed (Schoretsanitis 2020; Westin 2017).

If treatment for obsessive-compulsive disorder or major depressive disorder is initiated for the first time during pregnancy, fluvoxamine is not one of the preferred SSRIs (CANMAT [MacQueen 2016]; Larsen 2015). If pregnancy occurs during fluvoxamine treatment, changing to another SSRI can be considered if safe in relation to the patient's disease (Larsen 2015). Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006).

Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry to enroll; enrollment should be done as early in pregnancy as possible (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/).

Breastfeeding Considerations

Fluvoxamine is present in breast milk.

The relative infant dose (RID) of fluvoxamine has been calculated in review articles to be <2% of the weight-adjusted maternal dose (Berle 2011; Orsolini 2015). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).

In one review, the RID of fluvoxamine was calculated using pooled data from 12 mother/infant pairs providing an estimated daily infant dose via breast milk of 0.12 mg/day. The maternal dose and actual breast milk concentrations for the calculation were not provided (Berle 2011). A second review included information from 18 cases; maternal daily doses of fluvoxamine were 25 to 300 mg/day. The highest breast milk concentrations of fluvoxamine presented were 67 to 425 ng/mL following maternal doses of 50 to 150 mg/day from a study of 2 women 3 to 6 weeks postpartum, providing an RID of 0.8% to 1.38% (Orsolini 2015). Fluvoxamine has been detected in the serum of some breastfed infants (Orsolini 2015; Weissman 2004).

In one case report, mild vomiting, severe diarrhea, decreased sleep, and increased agitation in a fully breastfed infant was reported. The mother was initially treated with other selective serotonin reuptake inhibitors (SSRIs) beginning 8 weeks postpartum; however, treatment was changed to fluvoxamine 50 mg/day due to maternal side effects. After 2 days of fluvoxamine therapy, mild vomiting (2 to 3 times/day), severe diarrhea (15 times/day), decreased sleep and increased agitation were observed in the fully breastfed infant. Fluvoxamine was discontinued and symptoms resolved within 24 hours without treatment. One week later, fluvoxamine therapy was resumed, and the same symptoms occurred in the infant (Uguz 2015). Infants exposed to an SSRI via breast milk should be monitored for irritability and changes in sleep, feeding patterns, and behavior, as well as growth and development (ABM [Sriraman 2015]; Sachs 2013; Weissman 2004; WFSBP [Bauer 2013]).

Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010), however the underlying maternal illness may also influence this outcome (Grzeskowiak 2018). Untreated severe or chronic depression in the postpartum period also has negative effects on the mother and the infant (Slomian 2019).

Psychotherapy or other nonmedication therapies are recommended for the initial treatment of mild depression in breastfeeding patients; however, antidepressant medication is recommended when psychotherapy is not an option or when symptoms are moderate to severe. If a specific SSRI was used effectively during pregnancy, it can be continued while breastfeeding if no contraindications exist (ABM [Sriraman 2015]). According to the manufacturer, the decision to breastfeed during fluvoxamine therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. When first initiating an antidepressant in a breastfeeding patient, agents other than fluvoxamine are preferred (ABM [Sriraman 2015]; CANMAT [MacQueen 2016]; Larsen 2015).

Monitoring Parameters

Evaluate mental status, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks or other unusual changes in behavior; signs/symptoms of serotonin syndrome; akathisia; weight and BMI; hepatic function (baseline and as clinically indicated).

Mechanism of Action

Inhibits CNS neuron serotonin uptake; minimal or no effect on reuptake of norepinephrine or dopamine; does not significantly bind to alpha-adrenergic, histamine or cholinergic receptors

Pharmacokinetics

Onset of action:

Anxiety disorders (obsessive-compulsive, panic, and posttraumatic stress disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Issari 2016; Varigonda 2016; WFSBP [Bandelow 2012]); some experts suggest up to 12 weeks of treatment may be necessary for response, particularly in patients with obsessive-compulsive disorder and posttraumatic stress disorder (BAP [Baldwin 2014]; Katzman 2014; WFSBP [Bandelow 2012]).

Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009; Taylor 2006).

Distribution: Vd: ~25 L/kg

Protein binding: ~80%, primarily to albumin

Metabolism: Extensively hepatic via oxidative demethylation and deamination

Bioavailability: Immediate release: 53%; Extended release: 84%; not significantly affected by food.

Half-life elimination: ~14 to 16 hours; ~17 to 26 hours in the elderly

Time to peak, plasma: 3 to 8 hours

Excretion: Urine (~85% as metabolites; ~2% as unchanged drug)

Pharmacokinetics: Additional Considerations

Hepatic function impairment: For the IR tablets, a 30% decrease in clearance has been observed in patients with hepatic impairment compared with healthy subjects. Half-life and AUC increased by ~50% following a single dose of immediate release fluvoxamine in patients with alcoholic liver cirrhosis (van Harten 1993).

Pediatric: For the immediate-release tablets, area under the curve (AUC) and Cmax were 1.5- and 2.7-fold higher, respectively, in children 6 to 11 years of age. Female children had significantly higher AUC and Cmax compared with males. AUC and Cmax in adolescents 12 to 17 years of age were similar to adults and there were no gender differences.

Older adult: For the immediate-release tablets, compared with younger subjects, clearance is reduced by 50% and mean max plasma concentrations are 40% higher in the elderly.

Sex: For the extended-release capsules, the AUC and Cmax were increased by approximately 60% in healthy women compared with men.

Pricing: US

Capsule ER 24 Hour Therapy Pack (fluvoxaMINE Maleate ER Oral)

100 mg (per each): $10.18

150 mg (per each): $10.93

Tablets (fluvoxaMINE Maleate Oral)

25 mg (per each): $2.30

50 mg (per each): $2.57

100 mg (per each): $2.63 - $2.64

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Anwu (MY);
  • Avoxin (HR);
  • Depromel (JP);
  • Dumirox (DK, ES, IT, KR, UY);
  • Dumyrox (GR, PT);
  • Ervosal (EG);
  • Faverin (AE, AU, BH, CY, EG, GB, HK, IE, IQ, IR, JO, KW, LB, LY, MT, OM, PK, QA, SA, SG, SY, TH, TR, YE, ZA);
  • Favoxil (IL);
  • Fevalax (PY);
  • Fevarin (BG, CZ, EE, FI, HR, HU, IT, LT, LV, NL, NO, PL, RO, RU, SE, UA);
  • Floxyfral (AT, BE, CH, FR, LU);
  • Fluvohexal (DE);
  • Fluvoxia (TW);
  • Fluvoxim (PE);
  • Fluvoxin (IN, TH);
  • Fluxamine (EG);
  • Forezol (CR, DO, GT, HN, NI, PA, SV);
  • Foxa (IN);
  • Freevox (LK);
  • Genbou (TW);
  • Lote (TW);
  • Luvat (CL);
  • Luvox (AR, AU, BR, CL, CN, CR, DO, EC, GT, HN, ID, JP, MX, MY, NI, NZ, PA, PE, SV, TW, VE, VN, ZA);
  • Maveral (IT);
  • Movox (AU);
  • Relafin (BD);
  • Uvox (IN);
  • Voxam (AU);
  • Voxamin (CO);
  • Vuminix (CR, DO, GT, HN, MX, NI, PA, SV)


For country code abbreviations (show table)
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