Brand name: Luvox CR
Drug class: Selective Serotonin-reuptake Inhibitors
- Serotonin-reuptake Inhibitors
- SSRIs
VA class: CN609
Chemical name: O-(2-aminoethyl)oxime 5-methoxy-1-(4-(trifluoromethyl)phenyl)-1-pentanone (Z)-2-butenedioate (1:1)
Molecular formula: C₁₅H₂₁F₃N₂O₂•C₄H₄O₄
CAS number: 61718-82-9

Medically reviewed by Drugs.com on Feb 5, 2024. Written by ASHP.

Introduction

Antidepressant; selective serotonin-reuptake inhibitor (SSRI).

Uses for fluvoxaMINE

Obsessive-Compulsive Disorder (OCD)

Management of OCD; reduces but does not eliminate obsessions and compulsions.

Bulimia Nervosa

Has been used in the management of bulimia nervosa^{† [off-label]}.

fluvoxaMINE Dosage and Administration

General

• Allow at least 2 weeks to elapse between discontinuance of therapy with an MAO inhibitor and initiation of fluvoxamine therapy, and vice versa. (See Contraindications and also see Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Cautions.)

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

• Sustained therapy may be required; periodically reassess need for continued therapy.

• Avoid abrupt discontinuance. Taper dosage gradually and monitor for withdrawal symptoms. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions. (See Withdrawal of Therapy under Cautions.)

• Consider cautiously tapering dosage during third trimester of pregnancy prior to delivery. (See Pregnancy under Cautions.)

Administration

Oral Administration

Immediate-release Tablets

Administer orally once or twice daily without regard to meals.

Administer dosages ≤100 mg daily in adults or ≤50 mg daily in pediatric patients as a single daily dose at bedtime; higher dosages generally given in 2 divided doses, either as equally divided doses or as unequal doses with the larger dose given at bedtime.

Extended-release Capsules

Administer once daily at bedtime without regard to meals.

Do not crush or chew extended-release capsules.

Dosage

Available as fluvoxamine maleate; dosage is expressed in terms of the salt.

Pediatric Patients

OCD

Oral

Immediate-release tablets in children >8 years of age: Initially, 25 mg at bedtime. Increase dosage in 25-mg increments every 4–7 days, as tolerated, until maximum therapeutic benefit is achieved or up to a maximum dosage of 200 mg daily in children ≤11 years of age or 300 mg daily in adolescents ≥12 years of age. Girls ≤11 years of age may require lower dosages.

Extended-release capsules: Lowest available dose (i.e., 100 mg) may not be appropriate for pediatric patients not previously treated with fluvoxamine.

Optimum duration of therapy not established; may require several months or longer of sustained drug therapy. If therapy is prolonged, use the lowest possible dosage and periodically reassess need for continued therapy.

Adults

OCD

Oral

Immediate-release tablets: Initially, 50 mg at bedtime. May increase dosage in 50-mg increments every 4–7 days, as tolerated, until maximum therapeutic benefit is achieved or up to a maximum dosage of 300 mg daily. In clinical trials, efficacy demonstrated with dosages of 100–300 mg daily.

Extended-release capsules: Initially, 100 mg at bedtime. May increase dosage in increments of 50 mg daily at weekly intervals, as tolerated, until maximum therapeutic benefit is achieved up to a maximum of 300 mg daily.

Optimum duration of therapy not established; may require several months or longer of sustained drug therapy. If therapy is prolonged, use the lowest possible dosage and periodically reassess need for continued therapy.

Prescribing Limits

Pediatric Patients

OCD

Oral

Children ≤11 years of age: Maximum 200 mg daily.

Adolescents ≥12 years of age: Maximum 300 mg daily.

Adults

OCD

Oral

Maximum 300 mg daily.

Special Populations

Hepatic Impairment

OCD

Oral

Immediate-release tablets: Reduction of initial dosage and slow dosage titration may be appropriate.

Extended-release capsules: Initial dosage of 100 mg daily and slow dosage titration may be appropriate.

Renal Impairment

OCD

Oral

Limited evidence indicates that dosage modification is not necessary.

Geriatric Patients

Immediate-release tablets: Reduction of initial dosage (e.g., to 25 mg daily) and slow dosage titration may be appropriate.

Extended-release capsules: Initial dosage of 100 mg daily and slow dosage titration may be appropriate.

Related/similar drugs

sertraline, fluoxetine, venlafaxine, Zoloft, citalopram, Prozac, paroxetine

Cautions for fluvoxaMINE

Contraindications

• Concomitant therapy with alosetron, astemizole (no longer commercially available in the US), pimozide, ramelteon, terfenadine (no longer commercially available in the US), thioridazine, or tizanidine.

• Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor. (See Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Cautions and also see Interactions.)

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients, whether or not they are taking antidepressants; may persist until clinically important remission occurs. However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving fluvoxamine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms. If decision is made to discontinue therapy, taper fluvoxamine dosage as rapidly as is feasible but consider risks of abrupt discontinuance. (See Withdrawal of Therapy under Cautions.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, OCD) or nonpsychiatric disorders.

Bipolar Disorder

May unmask bipolar disorder. (See Activation of Mania or Hypomania under Cautions.) Fluvoxamine is not approved for use in treating bipolar depression.

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

MAO Inhibitors Interaction

Concomitant use of SSRIs and MAO inhibitors associated with serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes; these reactions have resembled serotonin syndrome or neuroleptic malignant syndrome (NMS). (See Contraindicationsand also see Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Cautions.)

Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions

Potentially life-threatening serotonin syndrome or NMS-like reactions reported with SSRIs and SNRIs, including fluvoxamine, but particularly with concurrent administration of other serotonergic drugs (e.g., 5-HT₁ receptor agonists [triptans]), drugs that impair serotonin metabolism (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. (See Contraindications under Cautions and also see Interactions.)

Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).

Severe serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuations in vital signs, and mental status changes.

Monitor patients receiving fluvoxamine for the development of serotonin syndrome or NMS-like signs and symptoms. If such signs and symptoms occur, immediately discontinue treatment with fluvoxamine and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, and initiate supportive and symptomatic treatment.

Sensitivity Reactions

Hypersensitivity Reactions

Possible allergic reaction, anaphylaxis, angioedema, or Stevens-Johnson syndrome.

General Precautions

CYP-mediated Interactions with Drugs that Prolong QT Interval

May increase plasma concentrations of astemizole (no longer commercially available in the US), pimozide, terfenadine (no longer commercially available in the US), or thioridazine and thereby increase risk of QT-interval prolongation and/or serious ventricular arrhythmias (e.g., torsades de pointes) associated with elevated plasma concentrations of the drugs. (See Interactions.)

Withdrawal of Therapy

Withdrawal effects (e.g., dysphoric mood, irritability, agitation, dizziness, sensory disturbances [e.g., paresthesias, such as electric shock sensations], anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania) reported following discontinuance of serotonergic antidepressants, particularly when discontinuance was abrupt. Events generally self-limiting, but serious cases reported.

Taper dosage gradually; monitor patients for withdrawal symptoms when discontinuing therapy. If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage then resume more gradual dosage reductions.

Abnormal Bleeding

Possible increased risk of bleeding with SSRIs, including fluvoxamine, and SNRIs; events ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Concomitant use of aspirin, NSAIAs, warfarin, or other anticoagulants may increase risk. (See Interactions.)

Activation of Mania or Hypomania

Possible activation of mania and hypomania; use with caution in patients with a history of mania. (See Bipolar Disorder under Cautions.)

Seizures

Possible risk of seizures; use with caution in patients with a history of seizures. Avoid use in patients with unstable epilepsy, and carefully monitor patients with controlled epilepsy. Discontinue if seizures occur or if seizure frequency increases during therapy.

Hyponatremia or SIADH

Possible hyponatremia during treatment with SSRIs, including fluvoxamine, and SNRIs; in many cases, SIADH is apparent cause. Increased risk in patients who are volume depleted, elderly, or taking diuretics. Initiate appropriate medical intervention and consider drug discontinuance in patients with symptomatic hyponatremia.

Concomitant Illnesses

Limited experience; use with caution in patients with concomitant illnesses affecting metabolism or hemodynamic response.

Safety in patients with recent MI or those with unstable heart disease not established.

Electroconvulsive Therapy (ECT)

Effects of concomitant use with ECT not systematically evaluated.

Specific Populations

Pregnancy

Category C.

Possible complications, sometimes severe and requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care, reported in neonates exposed to fluvoxamine, other SSRIs, or SNRIs late in the third trimester; may arise immediately upon delivery. (See General under Dosage and Administration.)

Conflicting findings from available studies evaluating possible risk of persistent pulmonary hypertension of the newborn (PPHN) following in utero exposure to SSRIs; currently unclear whether SSRI use during pregnancy can cause PPHN.

Consult joint APA and ACOG guidelines (at [Web]) for additional information on management of depression in women prior to conception and during pregnancy, including treatment algorithms.

Effect on labor and delivery unknown.

Lactation

Distributed into milk; discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <8 years of age for OCD or in pediatric patients with conditions other than OCD.

Safety and efficacy of immediate-release fluvoxamine maleate tablets in OCD established in a small 10-week, placebo-controlled trial in children and adolescents 8–17 years of age; majority of patients continued receiving fluvoxamine therapy for up to 1–3 years longer in an open-label extension. Adverse effects generally similar to those reported in adults. No substantial differences in efficacy in treatment of OCD in children ≥8 years of age relative to adults.

Extended-release fluvoxamine maleate capsules not systematically evaluated in pediatric patients.

Risks associated with extended use in children and adolescents with OCD not systematically evaluated. Evidence of safety derived from relatively short-term clinical studies and from extrapolation of experience gained with adult patients. Effects on growth, cognitive behavioral development, and maturation of children and adolescents unknown.

Decreased appetite and weight loss observed with use of SSRIs; monitor weight and growth regularly in children and adolescents receiving long-term fluvoxamine therapy.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, OCD, or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of fluvoxamine in a child or adolescent for any clinical use. (See Suicidality in the Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Clinically important hyponatremia reported in geriatric patients, who may be at greater risk for this adverse effect. (See Hyponatremia or SIADH under Cautions.)

Clearance is decreased by about 50% in geriatric patients compared with younger patients (see Elimination: Special Populations, under Pharmacokinetics). Consider a lower initial dosage and titrate dosage slowly during initiation of therapy.

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Possible reduced clearance; initiate therapy with a low dosage and titrate slowly with careful monitoring. (See Hepatic Impairment under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

In adults: Nausea, somnolence, insomnia, abnormal ejaculation, asthenia, nervousness, anorexia, anorgasmia, dyspepsia, diarrhea, sweating, tremor, vomiting, decreased libido, dry mouth, rhinitis, taste perversion, urinary frequency.

In pediatric patients with OCD: Agitation, depression, dysmenorrhea, flatulence, hyperkinesia, rash.

Drug Interactions

Extensively metabolized in the liver, principally by CYP1A2, 2C9, 2D6, and 3A4. Inhibits CYP1A2, 2C9, and 3A4; weak inhibitor of CYP2D6.

Drugs Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (increased plasma concentrations of CYP1A2, 2C9, 2D6, and 3A4 substrate) with drugs metabolized by these CYP isoenzymes.

Drugs Affecting Hemostasis

Potential pharmacologic interaction (increased risk of bleeding) with concomitant use of drugs that affect coagulation; use with caution. (See Abnormal Bleeding under Cautions.)

Drugs Associated with Serotonin Syndrome

Potential pharmacologic interaction (potentially serious, sometimes fatal serotonin syndrome or NMS-like reactions) with serotonergic agents. Avoid such use, or use with caution. (See Contraindicationsand see Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions under Cautions.) If serotonin syndrome or NMS occurs, immediately discontinue fluvoxamine and any concurrently administered serotonergic or antidopaminergic agents and initiate supportive and symptomatic treatment.

Specific Drugs

fluvoxaMINE Pharmacokinetics

Absorption

Bioavailability

Immediate-release tablets: Absolute bioavailability is 53%.

Extended-release capsules: Mean peak plasma concentrations were 38% lower and relative bioavailability was 84% compared with immediate-release tablets.

Onset

OCD therapeutic response evident within 2–3 weeks, with maximal effects after several months.

Food

Food does not substantially affect GI absorption or oral bioavailability.

Special Populations

In children 6–11 years of age receiving immediate-release tablets, steady-state plasma fluvoxamine concentrations are twofold to threefold higher than those in adolescents 12–17 years of age.

In girls 6–11 years of age receiving immediate-release tablets, AUC and peak plasma fluvoxamine concentrations were substantially higher than those in boys 6–11 years of age.

In geriatric patients receiving immediate-release tablets, mean peak plasma fluvoxamine concentrations are approximately 40% higher than those in younger adults.

Distribution

Extent

Distributes into breast milk.

Plasma Protein Binding

Approximately 80% (principally albumin).

Elimination

Metabolism

Extensively metabolized in the liver, principally via oxidative demethylation and deamination, to several inactive metabolites.

Metabolized principally by CYP1A2, 2C9, 2D6, and 3A4.

Elimination Route

Eliminated principally in urine (94%); approximately 2% as unchanged drug.

Half-life

15.6–16.3 hours (following multiple doses of immediate-release tablets or single 100-mg dose of extended-release capsules).

Special Populations

Hepatic impairment may reduce clearance of immediate-release tablets by 30%.

In geriatric patients receiving immediate-release tablets, elimination half-life is increased by 28–66% and clearance is reduced by approximately 50%.

Stability

Storage

Oral

Extended-release Capsules

Tight container at 25°C (may be exposed to 15–30°C). Avoid temperatures >30°C. Protect from high humidity.

Immediate-release Tablets

Tight container at 25°C (may be exposed to 15–30°C). Protect from high humidity.

Actions

• Mechanism of action in the management of OCD not clearly established, but may involve inhibition of serotonergic activity.

• More potent than clomipramine, desipramine, and fluoxetine as an SSRI with substantially greater selectivity in inhibiting serotonin versus norepinephrine reuptake than that of other SSRIs (e.g., fluoxetine, paroxetine, sertraline) and TCAs (e.g., clomipramine).

• Possesses virtually no affinity for α₁- or α₂-adrenergic, β-adrenergic, muscarinic, dopamine D₂, histamine H₁, GABA-benzodiazepine, opiate, 5-HT₁, or 5-HT₂ receptors.

Advice to Patients

• Importance of providing copy of written patient information (medication guide) each time fluvoxamine is dispensed. Importance of advising patients to read the patient information before taking fluvoxamine and each time the prescription is filled.

• Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk under Cautions.)

• Importance of instructing patients not to take fluvoxamine with an MAO inhibitor or within 14 days of stopping the drug, and vice versa.

• Importance of informing patients of potential risk of serotonin syndrome and NMS-like reactions, particularly with concurrent use of fluvoxamine and 5-HT₁ receptor agonists (triptans), tramadol, other serotonergic agents, or antipsychotic agents. Importance of immediately contacting clinician if signs and symptoms of these syndromes develop (e.g., restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, muscle stiffness, labile BP, diarrhea, coma, nausea, vomiting, confusion).

• Risk of allergic reactions (e.g., Stevens-Johnson syndrome); importance of notifying clinicians if rash, hives, or a related allergic phenomenon occurs during therapy.

• Risk of cognitive and psychomotor impairment; importance of exercising caution while operating hazardous machinery, including automobile driving, until patients gain experience with the drug’s effects.

• Risks associated with concomitant use with alcohol; importance of avoiding alcohol during fluvoxamine therapy.

• Risk of hyponatremia, especially in patients who are volume depleted, elderly, or taking diuretics.

• Importance of continuing fluvoxamine therapy even if improvement is evident within 2–3 weeks, unless directed otherwise by clinician.

• Potential for withdrawal effects when stopping fluvoxamine, especially with abrupt discontinuance of the drug.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., MAO inhibitors, alosetron, pimozide, ramelteon, thioridazine, tizanidine) and OTC drugs or herbal supplements, as well as any concomitant illnesses (e.g., liver disease) or personal or family history of suicidality or bipolar disorder. Importance of advising patients about the risk of bleeding associated with concomitant use of fluvoxamine with aspirin or other NSAIAs, warfarin, or other drugs that affect coagulation.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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