FLUoxetine (Lexi-Drugs)

ALERT: US Boxed Warning
  Suicidality and antidepressant drugs:
Pronunciation

(floo OKS e teen)

Brand Names: US

PROzac; PROzac Weekly [DSC]; Sarafem

Brand Names: Canada

ACCEL-FLUoxetine [DSC]; ACH-FLUoxetine; ACT FLUoxetine; APO-FLUoxetine; Auro-FLUoxetine; BCI FLUoxetine [DSC]; BIO-FLUoxetine; DOM-FLUoxetine; JAMP-FLUoxetine; Mar-FLUoxetine [DSC]; MINT-FLUoxetine; MYLAN-FLUoxetine [DSC]; Odan-FLUoxetine; PHL-FLUoxetine [DSC]; PMS-FLUoxetine; PRIVA-FLUoxetine; PRO-FLUoxetine; PROzac; Q-FLUoxetine [DSC]; RAN-FLUoxetine; RIVA-FLUoxetine; SANDOZ FLUoxetine; TEVA-FLUoxetine; VAN-FLUoxetine

Dosing: Adult

Note: In patients sensitive to adverse effects, some experts suggest lower starting doses of 5 to 10 mg/day and gradual titration in increments of no more than 10 mg, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Hirsch 2018c; Stein 2018; WFSBP [Bandelow 2012]).

Binge eating disorder (off-label use): Limited data available: Oral: Initial: 10 to 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg at intervals ≥1 week up to 80 mg/day (Arnold 2002a; Leombruni 2008; Sysko 2018).

Bipolar major depression: Oral: Initial: 20 mg once daily in the evening in combination with olanzapine or another second-generation antipsychotic; may increase dose gradually in 10 to 20 mg increments (Kupka 2018; Tohen 2003; WFSBP [Grunze 2010]; manufacturer’s labeling); usual dose range: 20 to 60 mg/day (Kupka 2018; manufacturer’s labeling). May also use the fixed-dose combination instead of the separate components. See Dosing conversion below for conversion to or from olanzapine/fluoxetine fixed-dose combination.

Body dysmorphic disorder (BDD) (off-label use): Oral: Initial: 20 mg once daily; may increase dose gradually based on response and tolerability in increments of 20 mg every 2 to 3 weeks to a usual dose of 70 to 80 mg/day by week 6 to 10 (Phillips 2002; Phillips 2018). Doses up to 120 mg/day, if tolerated, may be necessary in some patients for optimal response (Phillips 2018). Note: An adequate trial for assessment of effect in BDD is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks (Phillips 2018).

Bulimia nervosa: Oral: Initial: 20 mg once daily; may increase dose gradually (eg, at intervals ≥1 week) based on response and tolerability in 20 mg increments up to a target dose of 60 mg/day (Leombruni 2006).

Manufacturer’s labeling: Dosing in prescribing information may not reflect current clinical practice. Initial: 60 mg/day

Fibromyalgia, refractory (alternative agent) (off-label use): Note: For patients not responsive to first-line agents (EULAR [Macfarlane 2017]). Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in 10 to 20 mg increments at ≥2-week intervals up to 80 mg/day. Mean dose in clinical trials was 45 mg/day (Arnold 2002b; EULAR [Macfarlane 2017]). In patients with an insufficient response to first-line monotherapy, some experts suggest low-dose combination therapy (eg, fluoxetine 20 mg/day with a tricyclic antidepressant) (Goldenberg 1996; Goldenberg 2018).

Generalized anxiety disorder (off-label use): Limited data available: Oral: Initial: 10 to 20 mg once daily; may gradually increase dose based on response and tolerability in 10 to 20 mg increments at intervals of ≥1 week up to 60 mg/day (Bystritsky 2018; Hirsch 2018c)

Major depressive disorder (unipolar): Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in 20 mg increments at intervals ≥1 week up to a maximum dose of 80 mg/day (Fava 1998). Usual dose: 20 to 60 mg/day (APA 2010). Note: For treatment-resistant depression, combination with olanzapine or another second-generation antipsychotic may be used; in major depression with psychotic features, fluoxetine plus an antipsychotic is standard treatment (APA 2010; Brunner 2014; Rothschild 2004). May consider use of the fixed-dose combination instead of the separate components. See Dosing conversions below for conversion to or from the olanzapine/fluoxetine fixed-dose combination.

Obsessive-compulsive disorder: Oral: Initial: 10 to 20 mg once daily; may increase dose gradually in 20 mg increments at intervals ≥1 week based on response and tolerability; recommended range: 40 to 80 mg/day (APA [Koran 2007]; Romano 2001; Simpson 2018; manufacturer’s labeling). Based on clinical experience, some patients may require up to 120 mg/day for a response; however, adverse effects may increase (APA [Koran 2007]; Simpson 2018). Note: An adequate trial for assessment of effect in OCD is considered to be ≥6 weeks at maximum tolerated dose (Issari 2016).

Panic disorder: Oral: Initial: 5 to 10 mg once daily; after 3 to 7 days, gradually increase dose based on response and tolerability in 5 to 10 mg increments at intervals ≥1 week up to a usual dose of 20 to 40 mg/day (APA 2009). Maximum dose: 60 mg/day (manufacturer’s labeling).

Posttraumatic stress disorder (PTSD) (off-label use): Oral: Initial: 10 to 20 mg once daily; may increase dose based on response and tolerability in 10 to 20 mg increments at intervals ≥1 week up to 80 mg/day. Usual dosage range in clinical trials: 20 to 60 mg/day (Connor 1999; Martenyi 2002a).

Premature ejaculation (off-label use): Limited data available: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability after ≥1 week (some experts suggest 3- to 4-week titration intervals [Khera 2018]) to 40 mg once daily (Kara 1996).

Premenstrual dysphoric disorder (PMDD):

Continuous daily dosing regimen: Oral: Initial: 10 mg once daily; increase to usual effective dose of 20 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 30 mg/day may be necessary in some patients for optimal response (Casper 2018).

Intermittent regimens:

Luteal phase dosing regimen: Oral: Initial: 10 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 20 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 30 mg/day during the luteal phase may be necessary in some patients for optimal response (Casper 2018).

Symptom-onset dosing regimen (off-label dosing): Oral: Limited data available: Initial 10 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month, may increase dose based on response and tolerability up to 20 mg/day (Casper 2018).

Raynaud phenomena (alternative agent) (off-label use): Note: For use in patients who are resistant to or cannot tolerate vasodilators (EULAR [Kowal-Bielecka 2017]). Oral: 20 mg once daily (Coleiro 2001)

Social anxiety disorder (off-label use): Oral: Initial: 10 to 20 mg once daily; after ~6 weeks may gradually increase dose based on response and tolerability in 10 mg increments at intervals of ≥1 week up to 60 mg/day (Davidson 2004; Stein 2018)

Dosing conversion:

Delayed release (once-weekly formulation): Immediate-release fluoxetine 20 mg/day = delayed-release fluoxetine 90 mg/week. When converting from immediate-release fluoxetine daily dosing, initiate delayed-release fluoxetine (90 mg once weekly) 7 days after the last 20 mg/day dose of immediate-release fluoxetine. Patients must be stabilized on immediate-release fluoxetine 20 mg once daily prior to switching.

Olanzapine/fluoxetine fixed-dose combination: When using individual components of fluoxetine with olanzapine rather than fixed-dose combination product, corresponding approximate dosage equivalents are as follows:

Olanzapine 2.5 mg + fluoxetine 20 mg = combination strength 3/25

Olanzapine 5 mg + fluoxetine 20 mg = combination strength 6/25

Olanzapine 12.5 mg + fluoxetine 20 mg = combination strength 12/25

Olanzapine 5 mg + fluoxetine 50 mg = combination strength 6/50

Olanzapine 12.5 mg + fluoxetine 50 mg = combination strength 12/50

Discontinuation of therapy: When discontinuing, gradually taper the dose (eg, over 1 to 4 weeks) to minimize withdrawal symptoms and detect re-emerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower titration (eg, over 4 weeks) include prior history of antidepressant withdrawal symptoms, high doses of antidepressants, or treatment duration >3 weeks (APA 2010; Hirsch 2018a). If necessary, some clinicians allow for abrupt discontinuation based on fluoxetine’s long half-life (Hirsch 2018a). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), 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, and pharmacodynamics), and the degree of symptom control desired (Hirsch 2018b; Ogle 2013; WFSBP [Bauer 2013]).

Switching to or from an MAOI:

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

Allow 5 weeks to elapse between discontinuing fluoxetine and initiation of an MAOI.

Dosing: Geriatric

Major depressive disorder (unipolar): Oral: Some patients may require an initial dose of 10 mg once daily with dosage increases of 10 to 20 mg every several weeks as tolerated; should not be taken at night unless patient experiences sedation. Refer to adult dosing; use with caution given the long half-life of fluoxetine.

Dosing conversion: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment: Adult

Single-dose studies: Pharmacokinetics of fluoxetine and norfluoxetine were similar among subjects with all levels of impaired renal function, including anephric patients on chronic hemodialysis.

Chronic administration: Additional accumulation of fluoxetine or norfluoxetine may occur in patients with severely impaired renal function.

Not removed by hemodialysis; use of lower dose or less frequent dosing is not usually necessary.

Dosing: Hepatic Impairment: Adult

Elimination half-life of fluoxetine is prolonged in patients with hepatic impairment. A lower dose or less frequent dosing of fluoxetine should be used in these patients.

Cirrhosis patient: Administer a lower dose or less frequent dosing interval.

Compensated cirrhosis without ascites: Administer 50% of normal dose.

Dosing: Pediatric

Anxiety with associated phobias and panic attacks: Very limited data available: Children 2 to 6 years: Oral: 5 mg/dose or 0.25 mg/kg/dose once daily; adequate trial is considered to be 8 to 10 weeks; continuation of therapy should be evaluated at 6 to 9 months after initiation; dosing based on case report in a 2.5-year old child and expert recommendations (Gleason 2007)

Bulimia nervosa adjunct therapy with cognitive behavioral therapy: Limited data available: Children ≥12 years and Adolescents: Oral: Initial: 20 mg once daily for 3 days, then 40 mg once daily for 3 days, then 60 mg once daily; dosing based on an open-label study of 10 pediatric patients (age: 12 to 18 years) which showed significant decrease in number of weekly purges; other reports describe use in adolescents (Gable 2005; Kotler 2003; Rosen 2010)

Depression:

Manufacturer’s labeling: Children ≥8 years and Adolescents:

Lower weight Children: Oral: Initial: 10 mg once daily; usual daily dose: 10 mg/day; if needed, may increase dose to 20 mg once daily after several weeks; maximum daily dose: 20 mg/day

Higher weight Children and Adolescents: Oral: Initial: 10 to 20 mg once daily; in patients started at 10 mg once daily, may increase dose to 20 mg after 1 week; maximum daily dose: 20 mg/day

Alternate dosing: Limited data available: Lower initial dosing has been recommended by some experts (Dopheide 2006; Gleason 2007):

Children ≤11 years: Oral: Initial: 5 mg once daily; clinically, doses have been titrated up to 40 mg once daily in pediatric patients

Children ≥12 years and Adolescents: Oral: Initial: 10 mg once daily; clinically, doses have been titrated up to 40 mg once daily in pediatric patients

Depression associated with bipolar I disorder (in combination with olanzapine): Children ≥10 years and Adolescents: Oral: Initial: 20 mg in the evening; adjust dose, if needed, as tolerated; safety of fluoxetine doses >50 mg in combination with doses >12 mg of olanzapine has not been studied in pediatrics. Note: When using individual components of fluoxetine with olanzapine rather than fixed-dose combination product (Symbyax), approximate dosage correspondence is as follows:

Olanzapine 2.5 mg + fluoxetine 20 mg = Symbyax 3/25

Olanzapine 5 mg + fluoxetine 20 mg = Symbyax 6/25

Olanzapine 12.5 mg + fluoxetine 20 mg = Symbyax 12/25

Olanzapine 5 mg + fluoxetine 50 mg = Symbyax 6/50

Olanzapine 12.5 mg + fluoxetine 50 mg = Symbyax 12/50

Obsessive-compulsive disorder:

Children <7 years: Limited data available: Oral: Initial: 5 mg once daily (Gleason 2007)

Children ≥7 years and Adolescents: Oral:

Lower weight Children: Initial: 10 mg once daily; if needed, may increase dose after several weeks; usual daily dose: 20 to 30 mg/day; minimal experience with doses >20 mg/day; no experience with doses >60 mg/day

Higher weight Children and Adolescents: Initial: 10 mg once daily; increase dose to 20 mg once daily after 2 weeks; may increase dose after several more weeks, if needed; usual daily dose: 20 to 60 mg/day

Repetitive behavior associated with autism spectrum disorders (ASD): Limited data available: Children ≥5 years and Adolescents: Oral: Initial: 2.5 mg once daily for 7 days; then may titrate at weekly intervals using weight-based dosing: 0.3 mg/kg/day during week 2; followed by 0.5 mg/kg/day during week 3, up to a maximum of 0.8 mg/kg/day; dosing based on a double-blind, crossover, placebo-controlled trial in 39 pediatric patients (age: 5 to 16 years) which showed statistically significant improvement in behavior scores compared to placebo; mean final dose: 9.9 mg/day (range: 2.4 to 20 mg/day) or 0.36 ± 0.116 mg/kg/day (Hollander 2005)

Selective mutism: Limited data available: Children ≥5 years and Adolescents: Oral: Initial: 5 mg once daily for 7 days, then increase to 10 mg daily for 7 days, and then increase to 20 mg daily; may further titrate in 20 mg/day increments if needed every 2 weeks; maximum daily dose: 60 mg/day. Dosing is based on an open-label study of 21 pediatric patients (age: 5 to 14 years); positive responses were reported in 76% of patients and required a dose of at least 20 mg/day; mean final dose: 28.1 mg/day (1.1 mg/kg/day) (Dummitt 1996). Weight-based dosing has been reported in a double-blind placebo-controlled trial (treatment group: n=6; placebo: n=9; age: 6-12 years) using the following titration: 0.2 mg/kg/day for 1 week, then 0.4 mg/kg/day for 1 week, then 0.6 mg/kg/day for 10 weeks; mean final dose: 21.4 mg/day (Black1994). To fully assess therapeutic response, a therapeutic trial of at least 9 to 12 weeks or longer has been suggested (Black 1994; Dummitt 1996; Kaakeh 2008).

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of fluoxetine.

Allow 5 weeks to elapse between discontinuing fluoxetine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Use with other MAO inhibitors (linezolid or IV methylene blue):

Do not initiate fluoxetine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving fluoxetine and potential benefits outweigh potential risks, discontinue fluoxetine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 5 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume fluoxetine 24 hours after the last dose of linezolid or IV methylene blue.

Dosing: Renal Impairment: Pediatric

Children ≥7 years and Adolescents: Adjustment not routinely needed. With chronic administration, additional accumulation of fluoxetine or norfluoxetine may occur in patients with severely impaired renal function. Based on experience in adult patients, not removed by hemodialysis; use of lower dose or less frequent dosing is not usually necessary.

Dosing: Hepatic Impairment: Pediatric

Children ≥7 years and Adolescents: Elimination half-life of fluoxetine is prolonged in patients with hepatic impairment; lower doses or less frequent administration are recommended

Use: Labeled Indications

Bipolar major depression (excluding Sarafem): Acute treatment of major depressive episodes (in combination with olanzapine or other antipsychotics) (WFSBP [Grunze 2010]) associated with bipolar I disorder

Bulimia nervosa (excluding Sarafem): Acute and maintenance treatment of binge eating and vomiting behaviors in patients with moderate to severe bulimia nervosa

Major depressive disorder (unipolar) (excluding Sarafem): Acute and maintenance treatment of unipolar major depressive disorder (MDD)

Obsessive-compulsive disorder (excluding Sarafem): Acute and maintenance treatment of obsessions and compulsions in patients with obsessive-compulsive disorder

Panic disorder (excluding Sarafem): Acute treatment of panic disorder with or without agoraphobia

Premenstrual dysphoric disorder (Sarafem only): Treatment of premenstrual dysphoric disorder

Treatment-resistant depression (excluding Sarafem): Acute treatment of treatment-resistant depression (patients with MDD who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) in combination with olanzapine or other antipsychotics (APA 2010)

Use: Off-Label: Adult

  Binge eating disorderLevel of Evidence [C]

Data from a limited number of patients studied suggest that fluoxetine may be beneficial to improve binge frequency, weight loss, body mass index, and severity of illness in patients with binge eating disorder Ref.

  Body dysmorphic disorderLevel of Evidence [B]

Data from a double-blind, randomized, placebo-controlled trial support the use of fluoxetine in the treatment of body dysmorphic disorder (with or without delusions) Ref.

  Fibromyalgia, refractoryLevel of Evidence [B, G]

Data from 2 double-blind, randomized trials support the use of fluoxetine in the treatment of pain, depression, sleep disturbance, and other symptoms of fibromyalgia Ref.

Based on Canadian Pain Society guidelines on the management of fibromyalgia syndrome, antidepressants, including SSRIs such as fluoxetine, are suggested for treatment of pain and other symptoms of fibromyalgia. European League Against Rheumatism (EULAR) guidelines make a weak recommendation against use of SSRIs based on lack of efficacy. Access Full Off-Label Monograph

  Generalized anxiety disorderLevel of Evidence [G]

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety disorders, SSRIs are effective and recommended in the management of generalized anxiety disorder; however, evidence for fluoxetine is limited Ref.

  Posttraumatic stress disorderLevel of Evidence [B, G]

Data from double-blind, randomized controlled trials support the use of fluoxetine for acute treatment and relapse prevention in patients with posttraumatic stress disorder (PTSD) Ref.

Based on the American Psychiatric Association guidelines for the treatment of patients with acute stress disorder and PTSD and WFSBP guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, SSRIs (including fluoxetine) are effective and recommended as first-line treatments for the management of PTSD. In addition, the Veterans Affairs and Department of Defense guidelines for the management of PTSD and acute stress disorder, recommend use of fluoxetine in the management of PTSD for patients who choose not to engage in or are unable to access trauma-focused psychotherapy. Access Full Off-Label Monograph

  Premature ejaculationLevel of Evidence [C, G]

Data from a limited number of patients suggest that fluoxetine may have some benefit in the treatment of premature ejaculation Ref.

According to the International Society for Sexual Medicine guidelines, SSRIs such as fluoxetine are effective and recommended in the management of premature ejaculation. Access Full Off-Label Monograph

  Raynaud phenomenonLevel of Evidence [C, G]

Data from a limited number of patients suggest that fluoxetine may have some benefit in reducing the severity and frequency of Raynaud phenomenon attacks Ref.

Based on the EULAR recommendations for the treatment of systemic sclerosis, fluoxetine might be considered for the treatment of Raynaud phenomenon in patients with systemic sclerosis, particularly those who cannot tolerate or do not respond to vasodilators. Access Full Off-Label Monograph

  Selective mutismLevel of Evidence [C]

Data from a limited number of patients studied in an open-label clinical trial and a double-blind, randomized, placebo-controlled trial suggest that fluoxetine may be beneficial for the treatment of selective mutism in children and adolescents Ref.

  Social anxiety disorderLevel of Evidence [B, G]

Data from a large randomized, double-blind, placebo-controlled trial support the use of fluoxetine in the treatment of social anxiety disorder Ref.

Based on the WFSBP guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, SSRIs such as fluoxetine are effective and recommended for first-line treatment of social anxiety disorder; however, evidence for fluoxetine is more limited in comparison to other SSRIs.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Anxiety Disorders:

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Panic Disorder,” 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in Primary Care,” 2012

Bipolar Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Clinical Guidelines for the Management of Major Depressive Disorder in Adults,” October 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002.

Eating Disorders:

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Eating Disorders,” 2011

Obsessive-Compulsive Disorder (OCD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder,” 2007

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in Primary Care,” 2012

Posttraumatic Stress Disorder (PTSD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” 2004

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” Guideline Watch (March 2009)

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in Primary Care,” 2012

Administration: Oral

Administer without regard to meals.

Bipolar I disorder and treatment-resistant depression: Take once daily in the evening.

Major depressive disorder and obsessive compulsive disorder: Once daily doses should be taken in the morning, or twice daily (morning and noon).

Bulimia: Take once daily in the morning.

Administration: Pediatric

Oral: May be administered without regard to food

Indication specific:

Major depressive disorder and obsessive compulsive disorder: Take in the morning; if twice daily dosing, take at morning and noon

Bipolar I disorder and treatment-resistant depression (with concurrent olanzapine): Take in the evening

Bulimia: Take in the morning

Storage/Stability

All dosage forms should be stored at controlled room temperature. Protect from light.

Extemporaneously Prepared

Note: Commercial oral solution is available (4 mg/mL)

A 1 mg/mL fluoxetine oral solution may be prepared using the commercially available preparation (4 mg/mL). In separate graduated cylinders, measure 5 mL of the commercially available fluoxetine preparation and 15 mL of Simple Syrup, NF. Mix thoroughly in incremental proportions. For a 2 mg/mL solution, mix equal proportions of both the commercially available fluoxetine preparation and Simple Syrup, NF. Label “refrigerate”. Both concentrations are stable for up to 56 days.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, lack of appetite, dry mouth, fatigue, diarrhea, nightmares, insomnia, loss of strength and energy, hot flashes, flu-like symptoms, yawning, tremors, sweating a lot, or headache. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), agitation, irritability, panic attacks, behavioral changes, mood changes, passing out, tachycardia, abnormal heartbeat, dizziness, excessive weight gain, excessive weight loss, sexual dysfunction, decreased libido, increased thirst, seizures, bradycardia, bruising, bleeding, anxiety, menstrual changes, polyuria, change in amount of urine passed, abnormal movements, eye redness, eye edema, vision changes, eye pain, signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, prescriber or severe diarrhea), or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
  International issues:
Medication Guide and/or Vaccine Information Statement (VIS)

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

Fluoxetine tablets: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/202133s004s005lbl.pdf#page=40

Prozac, Prozac Weekly: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018936s103,021235s023lbl.pdf#page=28

Sarafem: http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021860s011lbl.pdf#page=33

Contraindications

Hypersensitivity to fluoxetine or any component of the formulation; use of MAO inhibitors intended to treat psychiatric disorders (concurrently, within 5 weeks of discontinuing fluoxetine, or within 2 weeks of discontinuing the MAO inhibitor); initiation of fluoxetine in a patient receiving linezolid or intravenous methylene blue; use with pimozide or thioridazine (Note:Thioridazine should not be initiated until 5 weeks after the discontinuation of fluoxetine.)

Canadian labeling: Additional contraindications (not in the US labeling): Initiation of fluoxetine within 2 weeks of thioridazine discontinuation

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Fluoxetine is FDA approved for the treatment of OCD in children ≥7 years of age and MDD in children ≥8 years of age.

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

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

Concerns related to adverse effects:

• Allergic events and rash: Fluoxetine use has been associated with occurrences of significant rash and allergic events, including vasculitis, lupus-like syndrome, laryngospasm, anaphylactoid reactions, and pulmonary inflammatory disease. Discontinue if underlying cause of rash cannot be identified.

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

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

• CNS effects: May cause insomnia, anxiety, nervousness, or anorexia.

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

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

• QT prolongation: QT prolongation and ventricular arrhythmia including torsades de pointes has occurred. Use with caution in patients with risk factors for QT prolongation (eg, congenital long QT syndrome, history of prolonged QT, family history of prolonged QT or sudden cardiac death), other conditions that predispose to arrhythmias (eg, hypokalemia, hypomagnesemia, recent MI, uncompensated heart failure, bradyarrhythmias or other arrhythmias, concomitant use of other agents that prolong QT interval), or increased fluoxetine exposure (eg, overdose, hepatic impairment, use of CYP2D6 inhibitors, poor CYP2D6 metabolizer status, concomitant use of other highly protein-bound drugs). Consider ECG monitoring when initiating therapy in patients with risk factors for QT prolongation and ventricular arrhythmia. Consider discontinuing fluoxetine if ventricular arrhythmia suspected and initiate cardiac evaluation.

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

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

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

• Weight loss: May cause anorexia and/or weight loss. Use caution in patients where weight loss is undesirable.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with a history of MI or unstable heart disease; experience in these patients is limited.

• Diabetes: Use with caution in patients with diabetes mellitus; may alter glycemic control and may require adjustment of antidiabetic medication; hypoglycemia and hyperglycemia has been observed during and after cessation of therapy, respectively.

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed in patients with cirrhosis.

• Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Fluoxetine monotherapy is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use with caution in patients with severe renal impairment; a lower dosage or less frequent dosing may be needed.

• Seizure disorders: Use with caution in patients with a previous seizure disorder or conditions predisposing to seizures such as brain damage or alcoholism.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: May also cause agitation, sleep disturbances, and excessive CNS stimulation in older adults. Given the long half-life and nonlinear disposition of the drug, use caution, particularly if they have systemic illness or are receiving multiple drugs for concomitant diseases.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [“Inactive” 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

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

• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

• Long half-life: Due to the long half-life of fluoxetine and its metabolites, the effects and interactions noted may persist for prolonged periods following discontinuation.

Geriatric Considerations

Fluoxetine’s potential stimulating and anorexic effects may be bothersome to some patients and has not been shown to be superior in efficacy to other SSRIs. The long half-life in the elderly makes it less attractive compared to other SSRIs. The elderly are more prone to SSRI/SNRI-induced hyponatremia.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence “suggestive” of efficacy but not of sufficient strength to “confirm” efficacy (Nelson 2011). Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects.

Warnings: Additional Pediatric Considerations

SSRI-associated behavioral activation (ie, restlessness, hyperkinesis, hyperactivity, agitation) is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults. Somnolence (including sedation and drowsiness) is more common in adults compared to children and adolescents (Safer 2006). SSRI-associated vomiting is two- to threefold more prevalent in children compared to adolescents and is more prevalent in adolescents compared to adults (Safer 2006). May cause abnormal bleeding (eg, ecchymosis, purpura, upper GI bleeding); use with caution in patients with impaired platelet aggregation and with concurrent use of aspirin, NSAIDs, or other drugs that affect coagulation. A recent report describes five children (age: 8 to 15 years) who developed epistaxis (n=4) or bruising (n=1) while receiving SSRI therapy (sertraline) (Lake 2000). Fluoxetine may cause decreased growth (smaller increases in weight and height) in children and adolescent patients; currently, no studies directly evaluate fluoxetine’s long-term effects on growth, development, and maturation of pediatric patients; periodic monitoring of height and weight in pediatric patients is recommended. Case reports of decreased growth in children receiving fluoxetine or fluvoxamine (n=4; age: 11.6 to 13.7 years) for 6 months to 5 years suggest a suppression of growth hormone secretion during SSRI therapy (Weintrob 2002).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Fluoxetine and its metabolite cross the human placenta. Available studies evaluating teratogenic effects following maternal use of fluoxetine in the first trimester have shown inconsistent results. An increased risk of cardiovascular events was observed in one study; however, no specific pattern was observed and a causal relationship has not been established. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, women who are pregnant may require dose adjustments of fluoxetine to achieve euthymia. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy.

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Breast-Feeding Considerations

Fluoxetine and its active metabolite (norfluoxetine) are present in breast milk.

Using pooled data, the relative infant dose (RID) of fluoxetine is reported as <12% of the weight-adjusted maternal dose (Berle 2011), but may be higher in specific infants (Lester 1993; Taddio 1996). In general, breastfeeding is considered acceptable when the RID 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). When an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Concentrations of norfluoxetine in breast milk should also be considered. Both fluoxetine and norfluoxetine can be detected in the serum of breastfeeding infants. In some rare cases, infant plasma concentrations of fluoxetine are up to 80% of the maternal concentration (Berle 2011).

Adverse events in the breastfeeding infant have been reported following maternal use of fluoxetine, including crying, sleep disturbance, vomiting, and watery stools. Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015). Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010).

When first initiating an antidepressant in a breastfeeding woman, agents other than fluoxetine are preferred. Women successfully treated with fluoxetine during pregnancy may continue use while breastfeeding if there are no other contraindications (Berle 2011). Because fluoxetine is present in breast milk, breastfeeding is not recommended by the manufacturer

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

As reported in adults, unless otherwise noted.

>10%:

Central nervous system: Insomnia (10% to 33%), headache (21%), drowsiness (5% to 17%), anxiety (6% to 15%), nervousness (8% to 14%), yawning (≤11%)

Endocrine & metabolic: Decreased libido (4% to 11%)

Gastrointestinal: Nausea (12% to 29%), diarrhea (8% to 18%), anorexia (4% to 17%), xerostomia (9% to 12%)

Neuromuscular & skeletal: Weakness (9% to 21%), tremor (3% to 13%)

Respiratory: Pharyngitis (10% to 11%)

1% to 10%:

Cardiovascular: Vasodilation (1% to 5%), palpitations (≥1%), prolonged Q-T interval on ECG (≥1%; QTcF ≥450 msec3), chest pain, hypertension

Central nervous system: Dizziness (9%), abnormal dreams (5%), agitation (children and adolescents: ≥2%), personality disorder (children and adolescents: ≥2%), abnormality in thinking (2%), chills (≥1%), emotional lability (≥1%), amnesia, confusion, sleep disorder

Dermatologic: Diaphoresis (7% to 8%), skin rash (4% to 6%), pruritus (3%)

Endocrine & metabolic: Hypermenorrhea (children and adolescents: ≥2%), increased thirst (children and adolescents: ≥2%), weight loss (2%), weight gain

Gastrointestinal: Dyspepsia (6% to 10%), constipation (5%), flatulence (3%), vomiting (3%), dysgeusia (≥1%), increased appetite

Genitourinary: Ejaculatory disorder (≤7%), impotence (≤7%), urinary frequency (children and adolescents: ≥2%), urination disorder (≥1%)

Neuromuscular & skeletal: Hyperkinesia (children and adolescents: ≥2%)

Ophthalmic: Visual disturbance (2%)

Otic: Otalgia, tinnitus

Respiratory: Flu-like symptoms (8% to 10%), sinusitis (5% to 6%), epistaxis (children and adolescents: ≥2%)

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, acne vulgaris, acute abdominal condition, akathisia, albuminuria, alopecia, amenorrhea, anaphylactoid reaction, anemia, angina pectoris, angle-closure glaucoma, aphthous stomatitis, aplastic anemia, arthritis, asthma, ataxia, atrial fibrillation, bruise, bruxism, bursitis, cardiac arrhythmia, cardiac failure, cataract, cerebrovascular accident, cholelithiasis, cholestatic jaundice, colitis, dehydration, delusions, depersonalization, dyskinesia, dysphagia, dysuria, ecchymoses, edema, eosinophilic pneumonitis, equilibrium disturbance, erythema multiforme, erythema nodosum, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal reaction (rare), gastritis, gastroenteritis, gastrointestinal ulcer, glossitis, gout, gynecological bleeding, gynecomastia, hallucination, hemolytic anemia (immune-related), hepatic failure, hepatic necrosis, hepatitis, hiccups, hostility, hypercholesteremia, hyperprolactinemia, hypersensitivity reaction, hypertonia, hyperventilation, hypoglycemia, hypokalemia, hyponatremia (possibly in association with SIADH), hypotension, hypothyroidism, immune thrombocytopenia, laryngeal edema, laryngospasm, leg cramps, lupus-like syndrome, malaise, melena, memory impairment, migraine, mydriasis, myocardial infarction, myoclonus, neuroleptic malignant syndrome (Stevens 2008), optic neuritis, orthostatic hypotension, ostealgia, pancreatitis, pancytopenia, paranoia, petechia, priapism, pulmonary embolism, pulmonary fibrosis, pulmonary hypertension, purpuric rash, renal failure, serotonin syndrome, sexual disorder (may persist after discontinuation), skin photosensitivity, Stevens-Johnson syndrome, suicidal ideation, syncope, tachycardia, thrombocytopenia, toxic epidermal necrolysis, vasculitis, ventricular tachycardia (including torsades de pointes), violent behavior

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (major), CYP2D6 (major), CYP2E1 (minor), CYP3A4 (minor);Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C19 (moderate), CYP2D6 (strong)

Drug Interactions 

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification

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

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

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

Amphetamines: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines. 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 Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. 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

ARIPiprazole: FLUoxetine may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of neuroleptic malignant syndrome may be increased. ARIPiprazole may enhance the serotonergic effect of FLUoxetine. This could result in serotonin syndrome. FLUoxetine may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose should be reduced by at least half, except when used adjunctively for depression. Consult full interaction monograph or aripiprazole prescribing information for complete details.Risk D: Consider therapy modification

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Risk D: Consider therapy modification

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

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

AtoMOXetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (adult doses — patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Benzhydrocodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone. Risk C: Monitor therapy

Beta-Blockers: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Penbutolol; Sotalol. Risk C: Monitor therapy

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

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor; this recommendation does not apply if treating major depressive disorder. Reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a CYP3A4 inhibitor.Risk D: Consider therapy modification

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

BuPROPion: FLUoxetine may enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of FLUoxetine. Risk C: Monitor therapy

BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Risk D: Consider therapy modification

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

CarBAMazepine: FLUoxetine may increase the serum concentration of CarBAMazepine. 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 may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Risk D: Consider therapy modification

Cimetidine: May increase the serum concentration of FLUoxetine. Risk C: Monitor therapy

Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Risk D: Consider therapy modification

Clarithromycin: FLUoxetine may enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of FLUoxetine. Risk C: Monitor therapy

CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Risk D: Consider therapy modification

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

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. 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

CYP2C19 Substrates (High risk with Inhibitors): CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2C9 Inducers (Moderate): May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Risk D: Consider therapy modification

CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Ajmaline; Dapoxetine; Indoramin; Tamoxifen; Timolol (Ophthalmic); Tropisetron. Risk D: Consider therapy modification

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

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Risk D: Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Risk X: Avoid combination

Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Risk D: Consider therapy modification

Dosulepin: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dosulepin. Risk X: Avoid combination

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Risk D: Consider therapy modification

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

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

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

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

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

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

Fosphenytoin: May enhance the QTc-prolonging effect of FLUoxetine. FLUoxetine may increase the serum concentration of Fosphenytoin. Risk D: Consider therapy modification

Galantamine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine. 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

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

Haloperidol: FLUoxetine may enhance the QTc-prolonging effect of Haloperidol. FLUoxetine may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk D: Consider therapy modification

HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. 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

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Indoramin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin. 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

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. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid. Risk D: Consider therapy modification

Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Risk D: Consider therapy modification

Lithium: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Risk D: Consider therapy modification

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

Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk X: Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Risk C: Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Risk D: Consider therapy modification

Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: Reduce metoclopramide dose to 5 mg 4 times daily (30 minutes before each meal and at bedtime) and limit the maximum daily dose to 20 mg if combined with strong CYP2D6 inhibitors. Risk D: Consider therapy modification

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

Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Risk D: Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Risk D: Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. 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

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

Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Risk C: Monitor therapy

NIFEdipine: FLUoxetine may enhance the adverse/toxic effect of NIFEdipine. Risk C: Monitor therapy

NiMODipine: FLUoxetine 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 using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification

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

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

Opioid Agonists: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Peginterferon Alfa-2b: May decrease the serum concentration of FLUoxetine. 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

Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Risk D: Consider therapy modification

Phenytoin: FLUoxetine may increase the serum concentration of Phenytoin. Risk C: Monitor therapy

Pimozide: FLUoxetine may enhance the QTc-prolonging effect of Pimozide. FLUoxetine may increase the serum concentration of Pimozide. Risk X: Avoid combination

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

Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. Management: Monitor for signs and symptoms of possible treatment failure with primaquine in patients who are taking strong CYP2D6 inhibitors. If efficacy of primaquine is compromised, may consider adjusting therapies. Risk D: Consider therapy modification

Propafenone: May enhance the QTc-prolonging effect of FLUoxetine. FLUoxetine may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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

QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). 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

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

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.Risk C: Monitor therapy

Serotonin Reuptake Inhibitor/Antagonists: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity. Risk D: Consider therapy modification

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Risk X: Avoid combination

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

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. 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: FLUoxetine may enhance the QTc-prolonging effect of Thioridazine. FLUoxetine 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

Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy

TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

Tricyclic Antidepressants: FLUoxetine may enhance the adverse/toxic effect of Tricyclic Antidepressants. FLUoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluoxetine. Risk D: Consider therapy modification

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

Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination

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

Valbenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. 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

Vortioxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level. Risk D: Consider therapy modification

Monitoring Parameters

Serum sodium in at-risk populations (as clinically indicated); blood glucose (for diabetic patients); liver and renal function (baseline and as clinically indicated); ECG assessment and periodic monitoring in patients with risk factors for QT prolongation and ventricular arrhythmia; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; signs/symptoms of serotonin syndrome; akathisia; sleep status

Reference Range

Therapeutic levels have not been well established.

Therapeutic: Fluoxetine: 100 to 800 ng/mL (SI: 289 to 2,314 nmol/L); Norfluoxetine: 100 to 600 ng/mL (SI: 289 to 1,735 nmol/L)

Toxic: Fluoxetine plus norfluoxetine: >2,000 ng/mL

Advanced Practitioners Physical Assessment/Monitoring

Taper dosage slowly when discontinuing. Assess mental status for depression, signs of clinical worsening, suicide ideation, anxiety, social functioning, mania, or panic attack.

Nursing Physical Assessment/Monitoring

Assess therapeutic response (eg, mental status, mode, affect) at beginning of therapy and periodically throughout. Monitor for CNS and gastrointestinal disturbances. Taper dosage slowly when discontinuing. Assess mental status for depression, signs of clinical worsening, suicide ideation, anxiety, social functioning, mania, or panic attack.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

PROzac: 10 mg, 20 mg, 40 mg

Generic: 10 mg, 20 mg, 40 mg

Capsule Delayed Release, Oral:

PROzac Weekly: 90 mg [DSC]

Generic: 90 mg

Solution, Oral:

Generic: 20 mg/5 mL (5 mL, 120 mL)

Tablet, Oral:

Sarafem: 10 mg, 20 mg [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]

Generic: 10 mg, 20 mg, 60 mg

Dosage Forms: Canada

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

Capsule, Oral:

PROzac: 10 mg, 20 mg [contains BRILLIANT BLUE FCF (FD&C BLUE #1), BUTYLPARABEN, EDETATE CALCIUM DISODIUM, METHYLPARABEN, PROPYLPARABEN]

Generic: 10 mg, 20 mg, 40 mg, 60 mg

Solution, Oral:

Generic: 20 mg/5 mL (120ea, 120ml)

Anatomic Therapeutic Chemical (ATC) Classification
  • N06AB03
Generic Available (US)

Yes

Pricing: US

Capsule, delayed release (FLUoxetine HCl Oral)

90 mg (per each): $39.21

Capsules (FLUoxetine HCl (PMDD) Oral)

10 mg (per each): $7.86

20 mg (per each): $8.06

Capsules (FLUoxetine HCl Oral)

10 mg (per each): $2.42 – $2.60

20 mg (per each): $2.48 – $2.67

40 mg (per each): $5.34 – $5.56

Capsules (PROzac Oral)

10 mg (per each): $18.47

20 mg (per each): $18.98

40 mg (per each): $37.97

Solution (FLUoxetine HCl Oral)

20 mg/5 mL (per mL): $0.98

Tablets (FLUoxetine HCl (PMDD) Oral)

10 mg (per each): $16.25

20 mg (per each): $16.25

Tablets (FLUoxetine HCl Oral)

10 mg (per each): $2.87

20 mg (per each): $4.20

60 mg (per each): $10.44 – $11.61

Tablets (Sarafem Oral)

10 mg (per each): $25.06

20 mg (per each): $25.06

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.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Onset of action: Depression: The onset of action is within a week; however, individual response varies greatly and full response may not be seen until 8 to 12 weeks after initiation of treatment.

Absorption: Well absorbed; delayed 1 to 2 hours with weekly formulation

Distribution: Vd: 12 to 43 L/kg

Protein binding: 95% to albumin and alpha1 glycoprotein

Metabolism: Hepatic, via CYP2C19 and 2D6, to norfluoxetine (activity equal to fluoxetine)

Half-life elimination: Adults:

Parent drug: 1 to 3 days (acute), 4 to 6 days (chronic), 7.6 days (cirrhosis)

Metabolite (norfluoxetine): 9.3 days (range: 4 to 16 days), 12 days (cirrhosis)

Time to peak, serum: 6 to 8 hours

Excretion: Urine (10% as norfluoxetine, 2.5% to 5% as fluoxetine)

Note: Weekly formulation results in greater fluctuations between peak and trough concentrations of fluoxetine and norfluoxetine compared to once-daily dosing (24% daily/164% weekly; 17% daily/43% weekly, respectively). Trough concentrations are 76% lower for fluoxetine and 47% lower for norfluoxetine than the concentrations maintained by 20 mg once-daily dosing. Steady-state fluoxetine concentrations are ~50% lower following the once-weekly regimen compared to 20 mg once daily. Average steady-state concentrations of once-daily dosing were highest in children ages 6 to <13 (fluoxetine 171 ng/mL; norfluoxetine 195 ng/mL), followed by adolescents ages 13 to <18 (fluoxetine 86 ng/mL; norfluoxetine 113 ng/mL); concentrations were considered to be within the ranges reported in adults (fluoxetine 91 to 302 ng/mL; norfluoxetine 72 to 258 ng/mL).

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: The half-life for fluoxetine and norfluoxetine is prolonged.

Pediatric: Average steady-state fluoxetine serum concentrations in children (n=10; 6 to <13 years of age) were 2-fold higher than in adolescents (n=11; 13 to <18 years of age); all patients received 20 mg/day; average steady-state norfluoxetine serum concentrations were 1.5-fold higher in the children compared with adolescents; differences in weight almost entirely explained the differences in serum concentrations.

Local Anesthetic/Vasoconstrictor Precautions

Although caution should be used in patients taking tricyclic antidepressants, no interactions have been reported with vasoconstrictors and fluoxetine, a nontricyclic antidepressant which acts to increase serotonin; no precautions appear to be needed. Fluoxetine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine 2% with Neo-Cobefrin]) be used with caution.

Dental Health Professional Considerations

Problems with SSRI-induced bruxism have been reported and may preclude their use; clinicians attempting to evaluate any patient with bruxism or involuntary muscle movement, who is simultaneously being treated with an SSRI drug, should be aware of the potential association (see Local Anesthetic/Vasoconstrictor Precautions)

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and taste perversion. Problems with SSRI-induced bruxism have been reported and may preclude their use. Clinicians attempting to evaluate any patient with bruxism or involuntary muscle movement, who is simultaneously being treated with an SSRI drug, should be aware of this potential association (see Effects on Bleeding and Dental Health Professional Considerations)

Effects on Bleeding

Selective serotonin reuptake inhibitors such as fluoxetine may impair platelet aggregation due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication. The risk of a bleeding complication can be increased by coadministration of other antiplatelet agents such as NSAIDs and aspirin.

Index Terms

Fluoxetine Hydrochloride

FDA Approval Date
December 29, 1987
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Dummit ES 3rd, Klein RG, Tancer NK, Asche B, Martin J. Fluoxetine treatment of children with selective mutism: an open trial. J Am Acad Child Adolesc Psychiatry. 1996;35(5):615-621.[PubMed 8935208]

Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, Dunner DL. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry. 1998;10(4):145-150.[PubMed 9988054]

Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry. 2006;67(Suppl 4):14-21.[PubMed 16683858]

Fitzcharles MA, Ste-Marie PA, Goldenberg DL, et al. 2012 Canadian guidelines for the diagnosis and management of fibromyalgia syndrome. http://fmguidelines.ca/. Published 2012. Accessed January 12, 2017.

Fluoxetine solution [prescribing information]. Greenville, SC: Pharmaceutical Associates, Inc; April 2017.

Fluoxetine tablets [prescribing information]. Hauppauge, NY: ScieGen Pharmaceuticals Inc; May 2018.

Goldenberg D, Mayskiy M, Mossey C, Ruthazer R, Schmid C. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum. 1996;39(11):1852-1859.[PubMed 8912507]

Goldenberg DL. Treatment of fibromyalgia in adults not responsive to initial therapies. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 21, 2018.

Grunze H, Vieta E, Goodwin GM, et al; WFSBP Task Force on Treatment Guidelines for Bipolar Disorders. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry. 2010;11(2):81-109. doi: 10.3109/15622970903555881.[PubMed 20148751]

Haddad PM. Antidepressant discontinuation syndromes. Drug Saf. 2001;24(3):183-197.[PubMed 11347722]

Hirsch M, Birnbaum RJ. Discontinuing antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 11, 2018a.

Hirsch M, Birnbaum RJ. Switching antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 11, 2018b.

Hirsch M, Birnbaum RJ. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 26, 2018c.

“Inactive” ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics (AAP) Committee on Drugs. Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Issari Y, Jakubovski E, Bartley CA, Pittenger C, Bloch MH. Early onset of response with selective serotonin reuptake inhibitors in obsessive-compulsive disorder: a meta-analysis. J Clin Psychiatry. 2016;77(5):605-611. doi: 10.4088/JCP.14r09758.[PubMed 27249090]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Kaakeh Y, Stumpf JL. Treatment of selective mutism: focus on selective serotonin reuptake inhibitors. Pharmacotherapy. 2008;28(2):214-224.[PubMed 18225967]

Kara H, Aydin S, Yücel M, Agargün MY, Odabaş O, Yilmaz Y. The efficacy of fluoxetine in the treatment of premature ejaculation: a double-blind placebo controlled study. J Urol. 1996;156(5):1631-1632.[PubMed 8863556]

Khera M, Cunningham GR. Treatment of male sexual dysfunction. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 24, 2018.

Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(7)(suppl):S5-S53.[PubMed 17849776]

Kowal-Bielecka O, Fransen J, Avouac J, et al; EUSTAR Coauthors. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76(8):1327-1339. doi: 10.1136/annrheumdis-2016-209909.[PubMed 27941129]

Kupka R. Rapid cycling bipolar disorder in adults: Treatment of major depression. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 1, 2018.

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Leombruni P, Amianto F, Delsedime N, Gramaglia C, Abbate-Daga G, Fassino S. Citalopram versus fluoxetine for the treatment of patients with bulimia nervosa: a single-blind randomized controlled trial. Adv Ther. 2006;23(3):481-494.[PubMed 16912031]

Leombruni P, Pierò A, Lavagnino L, Brustolin A, Campisi S, Fassino S. A randomized, double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with binge eating disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(6):1599-1605. doi: 10.1016/j.pnpbp.2008.06.005.[PubMed 18598735]

Lester BM, Cucca J, Andreozzi L, Flanagan P, Oh W. Possible association between fluoxetine hydrochloride and colic in an infant. J Am Acad Child Adolesc Psychiatry. 1993;32(6):1253-1255.[PubMed 8282672]

Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318-328. doi: 10.1136/annrheumdis-2016-209724.[PubMed 27377815]

Marshall AM, Nommsen-Rivers LA, Hernandez LL, et al, “Serotonin Transport and Metabolism in the Mammary Gland Modulates Secretory Activation and Involution,” J Clin Endocrinol Metab, 2010, 95(2):837-46.[PubMed 19965920]

Martenyi F, Brown EB, Zhang H, Prakash A, Koke SC. Fluoxetine versus placebo in posttraumatic stress disorder. J Clin Psychiatry. 2002a;63(3):199-206.[PubMed 11926718]

Martenyi F, Brown EB, Zhang H, Koke SC, Prakash A. Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder. Br J Psychiatry. 2002b;181:315-320.[PubMed 12356658]

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Prozac (fluoxetine) [prescribing information]. Indianapolis, IN: Eli Lilly and Company; March 2017.

Prozac (fluoxetine) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; July 2016.

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Sarafem (fluoxetine) [prescribing information]. Irvine, CA: Allergan USA; January 2017.

Sarafem Pulvules (fluoxetine) [prescribing information]. Rockaway, NJ: Eli Lilly and Company; August 9, 2006.

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Brand Names: International

Actan (CL, PY); Actisac (TH); Adef-XL (LK); Adep (PH); Adepssir (PH); Adofen (ES); Alzac (EG); Anextin (BH, QA); Ansi (ID); Ansilan (CO); Antiprestin (ID); Bellzac (IE); Biozac (BG); Boniflox (CR, DO, GT, HN, NI, PA, SV); Captaton (AR); Daforin (BR); Dagrilan (GR); Dawnex (LK, ZW); Deprexin (BM, BS, BZ, GY, HU, JM, SR, TT); Deprizac (PH); Deproxin (TH); Dominium (EC); Drafzin (PH); Elevamood (EG); Elizac (ID); Flocept (ET); Floxet (HK, HU, UY); Flozak (BH); Fluctin (DE); Fluctine (AT, CH); Fludac (BF, BJ, CI, ET, GH, GM, GN, IN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM); Fludec (LK); Fluketin (SG); Fluneurin (BH); Flunil (IN); Fluovex (MY); Fluox (NZ); Fluox-Puren (DE); Fluoxeren (IT); Fluoxone (SG); Fluronin (TW); Flush (BD); Flutin (AE, CO, KW, MY, QA, SA); Flutine (IL, TH); Fluval (HR); Flux (LV); Fluxen (TW, UA); Fluxet (DE); Fluxetin (HK); Fluxil (AE, CY, IQ, IR, JO, LY, MT, OM, SA, SG, SY, TR, YE); Fluzac (BD, IE); Fluzyn-20 (BH); Fontex (BE, DK, FI, IS, NO, SE); Fropine (KR); Fuloren (KR); Fuxetine (KR); Gerozac (IE); Huma-Fluoxetin (HU); Lanclic (KR); Linz (QA); Lorien (ZA); Lovan (AU); Luramon (ES); Margrilan (AE, CY, IQ, IR, JO, LY, OM, PH, SA, SG, SY, YE); Modipran (BD); Moltoben (CR, DO, GT, HN, NI, PA, SV); Motivest (PH); Neupax (CR, DO, EC, GT, HN, NI, PA, PE, SV); Nopres (ID); Nuzak (ZA); Nycoflox (EE); Octozac (EG); Olena (GB); Oxactin (MT); Oxedep (CN, ZW); Oxetin (BD); Oxetine (AE, JO, LB, SA); Plazeron (MT); Portal (HR, HU, UA); Praxin (HU); Prazac (KR); Prizma (IL); Prodep (IN, UA); Prolert (LK); Prozac (AE, AR, AU, BB, BE, BF, BJ, BR, CI, CL, CN, CZ, EG, ES, ET, FR, GB, GH, GM, GN, HK, HR, HU, IE, IL, IT, JO, KE, KR, LR, LU, MA, ML, MR, MT, MU, MW, NE, NG, NL, NZ, PE, PK, PT, QA, RO, RU, SA, SC, SD, SG, SK, SL, SN, TH, TN, TR, TZ, UG, VE, VN, ZM); Prozac 20 (KR, MY, PH, TW); Prozac Dispersible (KR); Prozac Weekly (BB, KR); Prozit (TR); Qualisac (HK); Reneuron (ES); Salipax (BM, BS, BZ, GY, JM, MY, PL, QA, SR, TT); Seronil (FI); Sinzac (TW); Symbyax (MX); U-Zet (TW); Youke (CN); ZAC (ID); Zactin (AU, SG, TW)

Fluoxetine (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(floo OKS e teen)

Brand Names: US

PROzac; PROzac Weekly [DSC]; Sarafem

Brand Names: Canada

Prozac

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug is not approved for use in all children. Talk with the doctor to be sure that this drug is right for your child.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat obsessive-compulsive problems.
  • It is used to treat mood problems caused by monthly periods.
  • It is used to treat eating problems.
  • It is used to treat panic attacks.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to fluoxetine or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Linezolid, methylene blue, pimozide, or thioridazine.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
  • If you are breast-feeding. Do not breast-feed while you take this drug.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • It may take several weeks to see the full effects.
  • This drug may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this drug with your other drugs.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Very bad and sometimes deadly reactions along with a rash have rarely happened with this drug. Lung, kidney, or liver problems have also happened. Call your doctor right away if you have a change in the amount of urine passed, dark urine, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, yellow skin or eyes, or shortness of breath.
  • Some people may have a higher chance of eye problems with this drug. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • A big weight gain or loss.
  • Sex problems like lowered interest in sex or ejaculation problems.
  • Erection that lasts more than 4 hours.
  • Seizures.
  • Dizziness.
  • Slow heartbeat.
  • Any unexplained bruising or bleeding.
  • Anxiety.
  • Very nervous and excitable.
  • More thirst.
  • Period (menstrual) changes.
  • Passing urine more often.
  • Trouble controlling body movements.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if you take this drug with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • A type of abnormal heartbeat (prolonged QT interval) has happened with this drug. Sometimes, this has led to another type of unsafe abnormal heartbeat (torsades de pointes). Call your doctor right away if you have a fast or abnormal heartbeat, or if you pass out.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Upset stomach or throwing up.
  • Not hungry.
  • Diarrhea.
  • Dry mouth.
  • Feeling sleepy.
  • Strange or odd dreams.
  • Trouble sleeping.
  • Feeling tired or weak.
  • Flu-like signs.
  • Yawning.
  • Hot flashes.
  • Feeling nervous and excitable.
  • Shakiness.
  • Sweating a lot.
  • Headache.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • Long-acting products:
  • Swallow whole. Do not chew, break, or crush.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature. Do not freeze.
  • Protect from light.
  • Keep lid tightly closed.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Fluoxetine (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(floo OKS e teen)

Brand Names: US

PROzac; PROzac Weekly [DSC]; Sarafem

Brand Names: Canada

Prozac

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
  • This drug is not approved for use in all children. Talk with the doctor to be sure that this drug is right for your child.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat obsessive-compulsive problems.
  • It is used to treat mood problems caused by monthly periods.
  • It is used to treat eating problems.
  • It is used to treat panic attacks.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is taking any of these drugs: Linezolid, methylene blue, pimozide, or thioridazine.
  • If your child has taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for certain other health problems in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If your child is taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask the doctor or pharmacist if you are not sure.
  • If your child is breast-feeding a baby:
  • Be sure your child does not breast-feed a baby while taking this drug.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • If your child has high blood sugar (diabetes), you will need to watch his/her blood sugar closely.
  • It may take several weeks to see the full effects.
  • This drug may affect how much of some other drugs are in the body. If your child is taking other drugs, talk with the doctor. Your child may need to have blood work checked more closely while taking this drug with other drugs.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • Some people may have a higher chance of eye problems with this drug. The doctor may want your child to have an eye exam to see if your child has a higher chance of these eye problems. Call the doctor right away if your child has eye pain, change in eyesight, or swelling or redness in or around the eye.
  • This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death. Talk with the doctor.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • If your child is pregnant:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
  • Taking this drug in the third trimester of pregnancy may lead to some health problems in the newborn. Talk with the doctor.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Seizures.
  • A big weight gain or loss.
  • Dizziness.
  • Slow heartbeat.
  • Any unexplained bruising or bleeding.
  • Anxiety.
  • Very nervous and excitable.
  • More thirst.
  • Passing urine more often.
  • Trouble controlling body movements.
  • Erection that lasts more than 4 hours.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if your child takes this drug with drugs for depression, migraines, or certain other drugs. Call your child’s doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; a fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • Very bad and sometimes deadly reactions along with a rash have rarely happened with this drug. Lung, kidney, or liver problems have also happened. Call the doctor right away if your child has a change in the amount of urine passed, dark urine, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, yellow skin or eyes, or shortness of breath.
  • A type of abnormal heartbeat (prolonged QT interval) has happened with this drug. Sometimes, this has led to another type of unsafe abnormal heartbeat (torsades de pointes). Call your child’s doctor right away if your child has a fast or abnormal heartbeat, or if your child passes out.
  • If your child has menstrual periods:
  • Period (menstrual) changes.
  • If your child is or may be sexually active:
  • Sex problems like lowered interest in sex or ejaculation problems.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Upset stomach or throwing up.
  • Not hungry.
  • Dry mouth.
  • Diarrhea.
  • Trouble sleeping.
  • Feeling sleepy.
  • Strange or odd dreams.
  • Feeling tired or weak.
  • Flu-like signs.
  • Yawning.
  • Hot flashes.
  • Feeling nervous and excitable.
  • Shakiness.
  • Sweating a lot.
  • Headache.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • All products:
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Long-acting products:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Liquid (solution):
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature. Do not freeze.
  • Store in a dry place. Do not store in a bathroom.
  • Protect from light.
  • Keep lid tightly closed.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.