Version October 2024
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.
Dosage guidance:
Dosing: Some experts suggest a lower starting dose of 25 mg daily and gradual titration in increments of ≤25 mg, particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).
Dosage form information: 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.
Binge eating disorder (off-label use): Oral: Immediate release: Initial: 50 mg once daily; increase dose based on response and tolerability up to 300 mg/day (Ref). Divide total daily doses >100 mg into twice-daily dosing (Ref); dosing frequencies of 3 times daily have also been used in a clinical trial with total daily doses of 300 mg/day (Ref).
Body dysmorphic disorder (off-label use): Oral: Immediate release: Initial: 50 mg once daily; may increase dose gradually based on response and tolerability in increments of 50 mg every 2 to 3 weeks to a usual dose of 300 mg/day by week 6 to 10 (Ref). Doses up to 450 mg/day, if tolerated, may be necessary in some patients for optimal response (Ref). Note: An adequate trial for assessment of effect is 12 to 16 weeks, including a dose of 300 mg for at least 4 of those weeks, if needed and tolerated (Ref).
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 (Ref).
Generalized anxiety disorder (off-label use):
Immediate release: Oral: Initial: 50 mg once daily; may 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 (Ref). Some experts maintain the initial therapeutic dose for 4 to 6 weeks to assess for efficacy before increasing further (Ref).
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 (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 (Ref).
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 (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 (Ref). Some experts maintain dose at 100 mg for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Posttraumatic stress disorder (PTSD) (off-label use): Oral: Immediate release: 75 mg twice daily (Ref).
Social anxiety disorder (off-label use): Oral:
Immediate release: Initial: 50 mg once daily; after 4 to 6 weeks at this dose, 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 (Ref).
Extended release: Initial: 100 mg once daily at bedtime; after 4 to 6 weeks at this dose, may increase in 50 mg increments at intervals of at least 1 week; usual dosage range: 100 to 300 mg daily; maximum dose: 300 mg/day (Ref)
Discontinuation of therapy:When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include prior history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
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 (Ref).
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.
There are no dosage adjustments provided in manufacturer's labeling. Limited data suggest fluvoxamine does not accumulate in patients with renal impairment.
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 (Ref).
Refer to adult dosing. Consider a lower initial dose; titrate slowly.
(For additional information see "Fluvoxamine: Pediatric drug information")
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 (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
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 (Ref).
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 (Ref). 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 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Limited data suggest fluvoxamine does not accumulate in patients with renal impairment.
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 (Ref).
Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent manic reaction or hypomania have been reported in adult patients with obsessive compulsive disorder and/or unipolar major depressive disorder (MDD) (many cases of bipolar disorder present in episodes of MDD) (Ref).
Mechanism: Non–dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy, but not thereafter (up to 4.6 years) (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Females (Ref)
Selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, may increase the risk of bleeding in adults and pediatric patients, particularly if used concomitantly with antiplatelets and/or anticoagulants. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematomas, petechiae, purpuric disease and epistaxis, to cerebrovascular accident, upper gastrointestinal hemorrhage, intracranial hemorrhage, abnormal uterine bleeding, and intraoperative bleeding, although conflicting evidence also exists (Ref).
Mechanism: Possibly via inhibition of serotonin-mediated platelet activation and subsequent platelet dysfunction. Fluvoxamine is considered to display moderate affinity for the serotonin reuptake receptor (Ref). SSRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).
Onset: Varied; bleeding risk is likely delayed for several weeks until SSRI-induced platelet depletion becomes clinically significant (Ref); although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory drugs (NSAIDs). For upper GI bleeding, some studies have found risk to be the highest in the first 28 to 30 days (Ref); whereas, another study reported a median time of onset of 25 weeks (Ref).
Risk factors:
• Concomitant use of anticoagulants and/or antiplatelets (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)
• Concomitant use of NSAIDs increases the risk for upper GI bleeding (Ref)
Limited data from observational studies involving mostly adults ≥50 years suggest selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of bone fractures (Ref).
Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by SSRIs on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity (Ref). An increased tendency for falls may also contribute to the increased risk of fractures associated with SSRIs (Ref).
Onset: Delayed; risk appears to increase after initiation and may continue to increase with long-term use. A meta-analysis found risk of fracture increased from 2.9% over 1 year to 5.4% over 2 years; within 5 years, risk increased to 13.4% (Ref).
Risk factors:
• Long-term use may be a risk factor (Ref)
Selective serotonin reuptake inhibitors are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia (including severe cases), predominantly in the elderly (Ref). Hyponatremia is reversible with discontinuation of therapy (Ref).
Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).
Onset: Intermediate; usually develops within the first few weeks of treatment (Ref).
Risk factors:
• Older age (Ref)
• Females (Ref)
• Concomitant use of diuretics (Ref)
• Low body weight (Ref)
• Lower baseline serum sodium concentration (Ref)
• Volume depletion (Ref)
• History of hyponatremia (potential risk factor) (Ref)
• Symptoms of psychosis (potential risk factor) (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-controlled study. AACG may cause symptoms including eye pain, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). In addition, SSRIs may be associated with mydriasis and an increased risk of cataract development (Ref).
Mechanism: AACG: Unclear; hypothesized SSRIs may increase the intraocular pressure via serotonergic effects on ciliary body muscle activation and pupil dilation (Ref).
Risk factors:
For AACG:
• Females (Ref)
• ≥50 years of age (slight increase) (Ref)
• Hyperopia (slight increase) (Ref)
• Personal or family history of AACG (Ref)
• Inuit or Asian descent (Ref)
Serotonin syndrome has been reported and typically occurs with coadministration of multiple medications that increase synaptic serotonin, but may also occur with a single agent at therapeutic doses (Ref). Serotonin syndrome may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).
Mechanism: Dose-related; overstimulation of serotonin receptors by medications that increase synaptic serotonin (Ref).
Onset: Rapid; in the majority of cases (74%), onset occurred within 24 hours of treatment initiation, overdose, or change in dose (Ref).
Risk factors:
• Concomitant use of drugs that increase serotonin synthesis, block serotonin reuptake and/or impair serotonin metabolism (eg, monamine oxidase inhibitors [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, are contraindicated.
Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorder in both men and women. The following adverse reactions have been associated with SSRI use: Ejaculatory disorder, orgasm disturbance, anorgasmia, erectile dysfunction, decreased libido, and loss of libido (Ref). Priapism and decreased genital sensation have also been reported with SSRIs (Ref).
Mechanism: Increases in serotonin may affect other hormones and neurotransmitters involved in sexual function; in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref). Elevated serotonin levels may also decrease nitrous oxide levels (due to inhibition of nitrous oxide synthase), resulting in impaired penile blood vessel relaxation and erectile dysfunction (Ref).
Onset: Varied; one study observed an onset of sexual dysfunction within the first 2 to 4 weeks of treatment with fluvoxamine (Ref).
Risk factors:
• Depression (sexual dysfunction is commonly associated with depression; SSRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years of age) in short-term studies. In adults ≥24 years of age, short-term studies did not show an increased risk of suicidal thinking and behavior, and in older adults (≥65 years of age) a decreased risk was observed. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs.
Mechanism: Not established; one of several postulated mechanisms is antidepressants may energize suicidal patients to act on impulses; another suggests that antidepressants may transiently worsen depressive symptoms leading to the emergence of suicidal thoughts and actions (Ref).
Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to long-term use (ie, >4 months).
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide is associated with major depression and may persist until remission occurs)
Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, shock-like sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability, mania), have been reported in adult and pediatric patients, primarily following abrupt discontinuation (Ref). Withdrawal symptoms may also occur following gradual tapering (Ref)
Mechanism: Withdrawal; due to reduced availability of serotonin in the CNS with decreasing levels of the selective serotonin reuptake inhibitor. Other neurotransmission systems, including increased glutamine and dopamine, may also be affected as well as the hypothalamic-pituitary-adrenal axis (Ref).
Onset: Intermediate; expected onset is 1 to 10 days (following either abrupt or tapered discontinuation) (Ref); in one study, withdrawal symptoms were most frequently reported on day 5 following fluvoxamine discontinuation (Ref).
Risk factors:
• Abrupt discontinuation (rather than gradual dosage reduction) of an antidepressant treatment that has lasted >3 weeks, particularly a drug with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
• High dose (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults, adolescents, and children. Frequency varies by dosage form (extended release and immediate release) and indication. Adverse reactions reported as a composite of all indications including off-label uses.
>10%:
Gastrointestinal: Anorexia (6% to 13%), diarrhea (11% to 18%), nausea (34% to 40%), xerostomia (10% to 14%)
Nervous system: Asthenia (14% to 26%), dizziness (11% to 12%), drowsiness (22% to 27%; literature suggests incidence occurs more frequently in adults compared to children and adolescents [Safer 2006]), headache (22% to 32%), insomnia (21% to 35%), nervousness (12%)
1% to 10%:
Cardiovascular: Edema (≥1%), hypertension (2%), hypotension (≥1%), palpitations (3%), syncope, vasodilation (3%; including feeling hot and flushing sensation)
Dermatologic: Acne vulgaris (2%), diaphoresis (7%), ecchymoses (4%)
Endocrine & metabolic: Decreased libido (2% to 10%; incidence higher in males), heavy menstrual bleeding (3%), weight gain (≥1%), weight loss (2%)
Gastrointestinal: Constipation (4% to 10%), dental caries (2% to 3%; including tooth abscess, toothache, and tooth loss), dysgeusia (2% to 3%), dyspepsia (8% to 10%), dysphagia (2%), flatulence (4%), gingivitis (2%), vomiting (5% to 6%; literature suggests prevalence is higher in adolescents compared to adults and is two- to threefold more prevalent in children compared to adults [Safer 2006])
Genitourinary: Anorgasmia (2% to 5%) (table 1), ejaculatory disorder (8% to 10%; including delayed ejaculation and ejaculation failure) (table 2), erectile dysfunction (2%) (table 3), polyuria (2%), sexual disorder (2% to 4%), urinary frequency (3%), urinary retention (1%)
|
Drug (Fluvoxamine) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Fluvoxamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
5% |
0% |
Adults |
Extended-release capsules |
Obsessive compulsive disorder |
124 |
124 |
|
2% |
0% |
Adults |
Immediate-release tablets |
Obsessive compulsive disorder or depression |
892 |
778 |
|
Drug (Fluvoxamine) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Fluvoxamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
10% |
0% |
Adults |
Extended-release capsules |
Obsessive compulsive disorder |
N/A |
N/A |
|
8% |
1% |
Adults |
Immediate-release tablets |
Obsessive compulsive disorder or depression |
N/A |
N/A |
|
Drug (Fluvoxamine) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Fluvoxamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
1% |
Adults |
Immediate-release tablets |
Obsessive compulsive disorder or depression |
N/A |
N/A |
Infection: Viral infection (2%)
Nervous system: Agitation (2%), amnesia (≥1%), anxiety (5% to 6%), apathy (3%), central nervous system stimulation (2%; including activation syndrome), changes in thinking (3%), chills (2%), depression (2%), hypertonia (2%), malaise, manic reaction (≥1%), myoclonus (≥1%), neurosis (2%), pain (10%), psychotic reaction (≥1%), tremor (5% to 6%), twitching (2%), yawning (2%)
Neuromuscular & skeletal: Hyperkinetic muscle activity (≥1%), hypokinesia (≥1%), myalgia (5%)
Ophthalmic: Amblyopia (2% to 3%; including blurred vision)
Respiratory: Dyspnea (2%), epistaxis (2%) (table 4), flu-like symptoms (3%), increased cough (≥1%), laryngitis (3%), pharyngitis (6%), sinusitis (≥1%), upper respiratory tract infection (9%)
|
Drug (Fluvoxamine) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Fluvoxamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
0% |
Adults |
Extended-release capsules |
Obsessive compulsive disorder |
124 |
124 |
<1%:
Cardiovascular: Acute myocardial infarction, angina pectoris, atrioventricular block, bradycardia, cardiac conduction delay, cardiac fibrillation, cardiomyopathy, cold extremity, embolism, irregular pulse, pericarditis, phlebitis, ST segment changes on ECG, supraventricular extrasystole
Dermatologic: Alopecia, eczema, exfoliative dermatitis, furunculosis, pallor, seborrhea, skin discoloration, skin photosensitivity, urticaria, xeroderma
Endocrine & metabolic: Dehydration, diabetes mellitus, goiter, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypoglycemia, hypokalemia, hypothyroidism, increased lactate dehydrogenase, increased libido, menopause, premenstrual syndrome, suppressed menstruation
Gastrointestinal: Ageusia, biliary colic, cholecystitis, cholelithiasis, colitis, eructation, esophagitis, fecal incontinence, gastritis, gastrointestinal hemorrhage, gastrointestinal ulcer, glossitis, hematemesis, hemorrhoids, hiccups, intestinal obstruction, melena, rectal hemorrhage, sialorrhea, stomatitis
Genitourinary: Abnormal uterine bleeding, anuria, cystitis, dysuria, hematuria, hemospermia, lactation, nocturia, oliguria, urination disorder (impaired urination), vaginal hemorrhage, vaginitis
Hematologic & oncologic: Anemia, leukocytosis, leukopenia, lymphadenopathy, purpuric disease, thrombocytopenia
Hepatic: Jaundice
Hypersensitivity: Hypersensitivity reaction
Nervous system: Abnormal dreams, agoraphobia, akathisia, akinesia, altered sense of smell, ataxia, central nervous system depression, cerebrovascular accident, coma, confusion, delirium, depersonalization, emotional lability, euphoria, extrapyramidal reaction, hallucination, hemiplegia, hostility, hypersomnia, hypochondriasis, hyporeflexia, hypotonia, hysteria, mutism, myasthenia, paralysis, paranoid ideation, phobia, psychosis, seizure, sleep disorder, slurred speech, stupor, suicidal tendencies (including suicidal ideation), trismus, unsteady gait, vertigo, withdrawal syndrome
Neuromuscular & skeletal: Arthralgia, arthritis, bursitis, dyskinesia, dystonia, muscle spasm, myopathy, neck pain, neck stiffness, tardive dyskinesia, torticollis
Ophthalmic: Accommodation disturbance, conjunctivitis, corneal ulcer, diplopia, dry eye syndrome, eye pain, mydriasis, visual field defect
Renal: Nephrolithiasis
Respiratory: Apnea, asthma, hemoptysis, hoarseness, hyperventilation, laryngismus, obstructive pulmonary disease, pneumonia, pulmonary infarct, respiratory congestion (upper airway)
Frequency not defined: Genitourinary: Priapism
Postmarketing:
Cardiovascular: Prolonged QT interval on ECG, Raynaud disease (Khouri 2016; Peiró 2007), shock, tachycardia, vasculitis, ventricular arrhythmia, ventricular tachycardia (including torsades de pointes)
Dermatologic: Bullous skin disease, Stevens-Johnson syndrome, toxic epidermal necrolysis (Wolkenstein 1993)
Endocrine & metabolic: Amenorrhea, hyponatremia (Gabriel 2009), porphyria, SIADH (Arinzon 2022)
Gastrointestinal: Bruxism, gastroesophageal reflux disease, glossalgia, pancreatitis
Hematologic & oncologic: Agranulocytosis, aplastic anemia, decreased white blood cell count, Henoch-Schonlein purpura
Hepatic: Hepatitis
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Abnormal gait, aggressive behavior, dysarthria, fatigue, hyperactive behavior (including agitation, hyperactivation, hyperkinesis, and restlessness occurring in children at a two- to threefold higher incidence compared to adolescents; it is more prevalent in adolescents compared to adults) (Safer 2006), homicidal ideation, hypomania (Rihmer 1996), impulsivity, intoxicated feeling, irritability, jitteriness, lethargy, loss of consciousness, neuroleptic malignant syndrome (Stevens 2008), outbursts of anger, parkinsonism, serotonin syndrome (Bastani 1996)
Neuromuscular & skeletal: Rhabdomyolysis (Zhang 2022)
Renal: Acute kidney injury, kidney impairment
Respiratory: Interstitial lung disease
Miscellaneous: Crying, fever
Concurrent use with alosetron, pimozide, thioridazine, or tizanidine; use of monoamine oxidase inhibitors (MAOIs) 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 IV methylene blue.
Note: Although fluvoxamine is contraindicated per the manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006a).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Concerns related to adverse effects:
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
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).
• 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.
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.
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
Yes
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.
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
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.
Oral: May be administered without regard to meals. Do not chew or crush extended-release capsule; swallow whole.
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/2023/021519s026lbl.pdf#page=32
Obsessive-compulsive disorder: Treatment of obsessive-compulsive disorder (OCD) in pediatric patients 8 to 17 years of age and adults.
Binge eating disorder; Body dysmorphic disorder; Bulimia nervosa; Generalized anxiety disorder; Major depressive disorder; Panic disorder; Posttraumatic stress disorder; Social anxiety disorder
FluvoxaMINE may be confused with flavoxATE, FLUoxetine, fluPHENAZine
Luvox may be confused with Lasix, Levoxyl, Lovenox
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 2023]).
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)
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Abrocitinib. 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
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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
Antiplatelet Agents (P2Y12 Inhibitors): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). 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
Epinephrine (Racemic): Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Epinephrine (Racemic). Risk X: Avoid combination
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
Fezolinetant: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
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
Gepirone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. 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
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. 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
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
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
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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
Psilocybin: Antidepressants may diminish the therapeutic effect of Psilocybin. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. 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
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
Venlafaxine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Venlafaxine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Venlafaxine. 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
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
Volanesorsen: May enhance the antiplatelet effect of Agents with Antiplatelet Effects. 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
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).
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/).
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).
Evaluate mental status, serum sodium in at-risk populations (as clinically indicated); closely monitor patients for depression, clinical worsening, suicidality, or unusual changes in behavior (eg, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, and social functioning), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); akathisia; weight and BMI; hepatic function (baseline and as clinically indicated); blood glucose (for diabetic patients).
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
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 2023a]); 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 2023a]; WFSBP [Bandelow 2023b]).
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 2006b).
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)
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.
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