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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
FLUoxetine may be confused with DULoxetine, fluvastatin, fluvoxamine, PARoxetine
Prozac® may be confused with Prilosec®, Prograf®, Proscar®, ProSom®, ProStep®
Sarafem® may be confused with Serophene®
International issues:
Fluoxin® [Czech Republic and Romania] may be confused with Floxin® which is a brand name for ofloxacin in the U.S.
Prozac® may be confused with Prazac® a brand of prazosin in Denmark
Reneuron® [Spain] may be confused with Remeron® a brand of mirtazapine in the U.S.
Pronunciation
(floo OKS e teen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes delayed release capsule
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder (MDD); treatment of binge-eating and vomiting in patients with moderate-to-severe bulimia nervosa; obsessive-compulsive disorder (OCD); premenstrual dysphoric disorder (PMDD); panic disorder with or without agoraphobia
Use: Unlabeled/Investigational
Selective mutism; treatment of mild dementia-associated agitation in nonpsychotic patients
Restrictions
An FDA-approved medication guide concerning the use of antidepressants in children, adolescents, and young adults must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and adolescents receiving this medication.
Pregnancy Risk Factor
C
Pregnancy Considerations
Due to adverse effects observed in animal studies, fluoxetine is classified as pregnancy category C. Fluoxetine and its metabolite cross the human placenta. Nonteratogenic effects in the newborn following SSRIs 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. An increased risk of low birth weight, lower APGAR scores, and blunted behavioral response to pain for a prolonged period after delivery have also been reported. Exposure to SSRIs after the twentieth week of gestation has been associated with persistent pulmonary hypertension of the newborn (PPHN). Adverse effects may be due to toxic effects of the SSRI or drug withdrawal without a taper. 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 increased doses of fluoxetine to achieve euthymia. Women treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued as compared to pregnant women who continue taking antidepressant medications. 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 healthcare provider, and pediatrician (ACOG, 2007). If treatment during pregnancy is required, consider tapering therapy during the third trimester in order to prevent withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy.
Lactation
Enters breast milk/not recommended (AAP rates “of concern”)
Breast-Feeding Considerations
Fluoxetine and its metabolite are excreted into breast milk and can be detected in the serum of breast-feeding infants. Concentrations in breast milk are variable. Colic, irritability, slow weight gain, and feeding and sleep disorders have been reported in nursing infants. The AAP considers fluoxetine to be a "drug for which the effect on the nursing infant is unknown but may be of concern." Breast-feeding is not recommended by the manufacturer.
Because the long-term effects on development and behavior have not been studied and adverse effects have been noted in some infants exposed, one should prescribe fluoxetine to a mother who is breast-feeding only when the benefits outweigh the potential risks.
Contraindications
Hypersensitivity to fluoxetine or any component of the formulation; patients currently receiving MAO inhibitors, pimozide, or thioridazine
Note: MAO inhibitor therapy must be stopped for 14 days before fluoxetine is initiated. Treatment with MAO inhibitors, thioridazine, or mesoridazine should not be initiated until 5 weeks after the discontinuation of fluoxetine.
Warnings/Precautions
Boxed Warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ?65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. 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. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. 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 healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• 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 is not FDA approved for the treatment of bipolar depression. Safety and efficacy in children <8 years of age (major depressive disorder) and <7 years of age (OCD) have not been established.
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.
• Anticholinergic effects: Relatively devoid of these side effects
• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• CNS effects: May cause insomnia, anxiety, nervousness, or anorexia.
• 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.
• Weight loss: May cause 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; use in these patients is limited.
• Diabetes: Use with caution in patients with diabetes mellitus; may alter glycemic control.
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
• Renal impairment: Use with caution in patients with renal impairment; clearance is decreased and plasma concentrations are increased; a lower dosage 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:
• Agents which lower seizure threshold: Use caution with concurrent therapy.
• Anticoagulants/Antiplatelets: Use caution with concomitant use of NSAIDs, ASA, or other drugs that affect coagulation; the risk of bleeding may be potentiated.
• CNS depressants: Use caution with concomitant therapy.
• MAO inhibitors: Potential for severe reaction when used with MAO inhibitors; autonomic instability, coma, death, delirium, diaphoresis, hyperthermia, mental status changes/agitation, muscular rigidity, myoclonus, neuroleptic malignant syndrome features, and seizures may occur.
• Serotonin syndrome: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans) or agents which reduce fluoxetine's metabolism. Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
• Thioridazine: Fluoxetine may elevate plasma levels of thioridazine; increasing risk of QTc interval prolongation; this may lead to serious ventricular arrhythmias, such as torsade de pointes-type arrhythmias, and sudden death. Concurrent use is contraindicated.
Special populations:
• Elderly: Use caution in elderly patients; risk of hyponatremia and other adverse events may be increased.
Other warnings/precautions:
• 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.
• Withdrawal syndrome: May cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Upon discontinuation of fluoxetine therapy, gradually taper dose. If intolerable symptoms occur following a decrease in dosage or upon discontinuation of therapy, then resuming the previous dose with a more gradual taper should be considered.
Adverse Reactions
Percentages listed for adverse effects as reported in placebo-controlled trials and were generally similar in adults and children; actual frequency may be dependent upon diagnosis and in some cases the range presented may be lower than or equal to placebo for a particular disorder.
>10%:
Central nervous system: Insomnia (10% to 33%), headache (21%), anxiety (6% to 15%), nervousness (8% to 14%), somnolence (5% to 17%)
Endocrine & metabolic: Libido decreased (1% to 11%)
Gastrointestinal: Nausea (12% to 29%), diarrhea (8% to 18%), anorexia (4% to 11%), xerostomia (4% to 12%)
Neuromuscular & skeletal: Weakness (7% to 21%), tremor (3% to 13%)
Respiratory: Pharyngitis (3% to 11%), yawn (<1% to 11%)
1% to 10%:
Cardiovascular: Vasodilation (1% to 5%), fever (2%), chest pain, hemorrhage, hypertension, palpitation
Central nervous system: Dizziness (9%), dream abnormality (1% to 5%), thinking abnormality (2%), agitation, amnesia, chills, confusion, emotional lability, sleep disorder
Dermatologic: Rash (2% to 6%), pruritus (4%)
Endocrine & metabolic: Ejaculation abnormal (<1% to 7%), impotence (<1% to 7%)
Gastrointestinal: Dyspepsia (6% to 10%), constipation (5%), flatulence (3%), vomiting (3%), weight loss (2%), appetite increased, taste perversion, weight gain
Genitourinary: Urinary frequency
Ocular: Vision abnormal (2%)
Otic: Ear pain, tinnitus
Respiratory: Sinusitis (1% to 6%)
Miscellaneous: Flu-like syndrome (3% to 10%), diaphoresis (2% to 8%)
<1%, postmarketing and/or case reports: Acne, albuminuria, allergies, alopecia, amenorrhea, anaphylactoid reactions, anemia, angina, aphthous stomatitis, arrhythmia, arthritis, asthma, bone pain, bruising, bursitis, cataract, CHF, cholelithiasis, cholestatic jaundice, colitis, dehydration, dyskinesia, dysphagia, ecchymosis, edema, eosinophilic pneumonia, epistaxis, erythema multiforme, erythema nodosum, esophagitis, euphoria, exfoliative dermatitis, extrapyramidal symptoms (rare), gastritis, glossitis, gout, gynecomastia, hallucinations, hepatic failure/necrosis, hemorrhage, hiccup, hostility, hypercholesteremia, hyperprolactinemia, hyperventilation, hypoglycemia, hypokalemia, hyponatremia (possibly in association with SIADH), hypotension, hypothyroidism, immune-related hemolytic anemia, kidney failure, laryngospasm, leg cramps, liver function test abnormalities, lupus-like syndrome, malaise, migraine, misuse/abuse, MI, neuroleptic malignant syndrome (NMS), optic neuritis, pancreatitis, pancytopenia, photosensitivity reaction, postural hypotension, priapism, pulmonary embolism, pulmonary fibrosis, pulmonary hypertension, QT prolongation, serotonin syndrome, Stevens-Johnson syndrome, suicidal ideation, syncope, tachycardia, tinnitus, thrombocytopenia, thrombocytopenic purpura, vasculitis, ventricular tachycardia (including torsade de pointes)
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (major), 2C19 (minor), 2D6 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (moderate), 2B6 (weak), 2C9 (weak), 2C19 (moderate), 2D6 (strong), 3A4 (weak)
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alpha-/Beta-Blockers: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Alpha-/Beta-Blockers. Risk C: Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). This may cause serotonin syndrome. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Benzodiazepines (metabolized by oxidation): Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Benzodiazepines (metabolized by oxidation). Risk C: Monitor therapy
Beta-Blockers: Selective Serotonin Reuptake Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Carteolol; Esmolol; Levobunolol; Metipranolol; Nadolol; Penbutolol. 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. Risk C: Monitor therapy
Carbamazepine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Carbamazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes. Carbamazepine may increase the metabolism of Selective Serotonin Reuptake Inhibitors. Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Risk D: Consider therapy modification
Cimetidine: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Clozapine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Clozapine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Coumarin Derivatives: Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Coumarin Derivatives. Risk C: Monitor therapy
CYP1A2 Substrates: CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP2C19 Substrates: CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inducers). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inhibitors). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk with Highly Effective Inhibitors). Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Dextromethorphan. Risk D: Consider therapy modification
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Galantamine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Galantamine. Risk C: Monitor therapy
Haloperidol: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Haloperidol. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Lithium: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Lithium. Risk C: Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Exceptions: Azithromycin; Dirithromycin [Off Market]; Spiramycin. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Methadone: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Methadone. Fluvoxamine appears to be the only interacting SSRI. Risk D: Consider therapy modification
Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Risk D: Consider therapy modification
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
NSAID (COX-2 Inhibitor): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk D: Consider therapy modification
NSAID (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). Risk D: Consider therapy modification
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Phenytoin: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Phenytoin. Risk D: Consider therapy modification
Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Management: Use of pimozide with fluvoxamine, paroxetine, and sertraline is contraindicated. Risk D: Consider therapy modification
Propafenone: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Propafenone. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
Quinidine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Quinidine. Fluvoxamine appears to be the only SSRI of concern. Risk D: Consider therapy modification
Risperidone: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Risperidone. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents 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. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Tramadol: Selective Serotonin Reuptake Inhibitors may enhance the neuroexcitatory and/or seizure-potentiating effect of Tramadol. Tramadol may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk D: Consider therapy modification
Tricyclic Antidepressants: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk D: Consider therapy modification
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression). Depressed patients should avoid/limit intake.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
All dosage forms should be stored at controlled room temperature of 15°C to 30°C (50°F to 86°F). Oral liquid should be dispensed in a light-resistant container.
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 8-12 weeks after initiation of treatment.
Absorption: Well absorbed; delayed 1-2 hours with weekly formulation
Distribution: Vd: 12-43 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: 1-3 days (acute), 4-6 days (chronic), 7.6 days (cirrhosis)
Metabolite (norfluoxetine): 9.3 days (range: 4-16 days), 12 days (cirrhosis)
Time to peak, serum: 6-8 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 91-302 ng/mL; norfluoxetine 72-258 ng/mL).
Dosage
Oral: Note: Upon discontinuation of fluoxetine therapy, gradually taper dose. If intolerable symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate.
Children:
Depression: 8-18 years: 10-20 mg/day; lower-weight children can be started at 10 mg/day, may increase to 20 mg/day after 1 week if needed
Obsessive-compulsive disorder: 7-18 years: Initial: 10 mg/day; in adolescents and higher-weight children, dose may be increased to 20 mg/day after 2 weeks. Range: 10-60 mg/day.
Selective mutism (unlabeled use):
<5 years: No dosing information available
5-18 years: Initial: 5-10 mg/day; titrate upwards as needed (usual maximum dose: 60 mg/day)
Adults: 20 mg/day in the morning; may increase after several weeks by 20 mg/day increments; maximum: 80 mg/day; doses >20 mg may be given once daily or divided twice daily. Note: Lower doses of 5-10 mg/day have been used for initial treatment.
Usual dosage range:
Bulimia nervosa: 60-80 mg/day
Depression: 20-40 mg/day; patients maintained on Prozac® 20 mg/day may be changed to Prozac® Weekly™ 90 mg/week, starting dose 7 days after the last 20 mg/day dose
Obsessive-compulsive disorder: 40-80 mg/day
Panic disorder: Initial: 10 mg/day; after 1 week, increase to 20 mg/day; may increase after several weeks; doses >60 mg/day have not been evaluated
Premenstrual dysphoric disorder (Sarafem™): 20 mg/day continuously, or 20 mg/day starting 14 days prior to menstruation and through first full day of menses (repeat with each cycle)
Elderly: Depression: Some patients may require an initial dose of 10 mg/day with dosage increases of 10 and 20 mg every several weeks as tolerated; should not be taken at night unless patient experiences sedation
Dosing adjustment in renal impairment:
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
Hemodialysis: Not removed by hemodialysis; use of lower dose or less frequent dosing is not usually necessary.
Dosing adjustment in hepatic impairment: Elimination half-life of fluoxetine is prolonged in patients with hepatic impairment; a lower or less frequent dose of fluoxetine should be used in these patients
Cirrhosis patients: Administer a lower dose or less frequent dosing interval
Compensated cirrhosis without ascites: Administer 50% of normal dose
Monitoring Parameters
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; akathisia, sleep
Reference Range
Therapeutic levels have not been well established
Therapeutic: Fluoxetine: 100-800 ng/mL (SI: 289-2314 nmol/L); Norfluoxetine: 100-600 ng/mL (SI: 289-1735 nmol/L)
Toxic: Fluoxetine plus norfluoxetine: >2000 ng/mL
Dietary Considerations
May be taken with or without food.
Patient Education
Take exactly as directed; do not increase dose or frequency. It may take 2-3 weeks to achieve desired results. Take once-a-day dose in the morning to reduce incidence of insomnia. Avoid alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); constipation (increased exercise, fluids, fruit, or fiber may help); anorexia (maintain regular dietary intake to avoid excessive weight loss); or postural hypotension (use caution when climbing stairs or changing position from lying or sitting to standing). If you have diabetes, monitor serum glucose closely (may cause hypoglycemia). Report persistent CNS effects (nervousness, restlessness, insomnia, anxiety, excitation, suicide ideation, headache, sedation); thoughts of suicide; rash or skin irritation; muscle cramping, tremors, or change in gait; respiratory depression or respiratory difficulty; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Breast-feeding is not recommended.
Geriatric Considerations
Fluoxetine's favorable side effect profile makes it a useful alternative to the traditional tricyclic antidepressants. Its potential stimulating and anorexic effects may be bothersome to some patients and has not been shown to be superior in efficacy to the traditional tricyclic antidepressants or other SSRIs. The long half-life in the elderly makes it less attractive compared to other SSRIs. Data from a clinical trial comparing fluoxetine to tricyclics suggest that fluoxetine is significantly less effective than nortriptyline in hospitalized elderly patients with unipolar major affective disorder, especially those with melancholia and concurrent cardiovascular diseases. As with other SSRIs, fluoxetine has been associated with hyponatremia in elderly patients.
Additional Information
ECG may reveal S-T segment depression. Not shown to be teratogenic in rodents; 15-60 mg/day, buspirone and cyproheptadine, may be useful in treatment of sexual dysfunction during treatment with a selective serotonin reuptake inhibitor.
Weekly capsules are a delayed release formulation containing enteric-coated pellets of fluoxetine hydrochloride, equivalent to 90 mg fluoxetine. Therapeutic equivalence of weekly formulation with daily formulation for delaying time to relapse has not been established.
Anesthesia and Critical Care Concerns/Other Considerations
SSRIs are relatively safe compared to other antidepressants in patients with cardiovascular disease.
Cardiovascular Considerations
SSRIs alone are relatively safe compared to other antidepressants in patients with cardiovascular disease. SSRIs may increase the risk of QT prolongation/torsade de pointes associated with other drugs administered concurrently. Fluoxetine is being evaluated in experimental studies for vasovagal syncope. Fluoxetine may decrease the metabolism of thioridazine possibly predisposing to thioridazine-induced QT interval prolongation. Thioridazine should not be used in combination with fluoxetine and should be dosed at least 5 weeks after fluoxetine is discontinued.
Dental Health: 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.
Dental Health: Vasoconstrictor/Local Anesthetic 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, levonordefrin [Neo-Cobefrin®]) be used with caution.
Mental Health: Child/Adolescent Considerations
A study in children 8-15 years of age with obsessive compulsive disorder (n=14) used a fixed dose of 20 mg/day (Riddle, 1992). A study of children 10-18 years of age with obsessive compulsive symptoms and Tourette's syndrome (n=5) used 20-40 mg/day (Kurlan, 1993). Six children 6-12 years of age with selective mutism were treated with initial doses of 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 (Black, 1994). Twenty-one children (mean age: 8.2 years) with selective mutism received a mean end dose of 28.1 mg (10-60 mg) in a 9 week open trial (Dummit, 1996). Ninety-six outpatients 7-17 years of age with nonpsychotic major depression received 20 mg/day (Emslie, 1997); further studies are needed.
Black B and Uhde TW, “Treatment of Elective Mutism With Fluoxetine: A Double Blind, Placebo-Controlled Study,” J Am Acad Child Adolesc Psychiatry, 1994, 33(7):1000-6.
Dummit ES 3rd, Klein RG, Tancer NK, et al, “Fluoxetine Treatment of Children With Selective Mutism: An Open Trial,” J Am Acad Child Adolesc Psychiatry, 1996, 35(5):615-21.
Emslie GJ, Rush AJ, Weinberg WA, et al, “A Double-Blind, Randomized, Placebo-Controlled Trial of Fluoxetine in Children and Adolescents With Depression,” Arch Gen Psychiatry, 1997, 54(11):1031-7.
Kurlan R, Como PG, Deeley C, et al, “A Pilot Controlled Study of Fluoxetine for Obsessive-Compulsive Symptoms in Children With Tourette's Syndrome,” Clin Neuropharmacol, 1993, 16(2):167-72.
Riddle MA, Scahill L, King RA, et al, “Double-Blind, Crossover Trial of Fluoxetine and Placebo in Children and Adolescents With Obsessive-Compulsive Disorder,” J Am Acad Child Adolesc Psychiatry, 1992, 31(6):1062-9.
Mental Health: Comment
The SSRIs as a class are generally considered to be safe and equally effective. For the management of depression, these drugs display a flat dose-response curve. Allow sufficient dose-response time (6-12 weeks). Differences lie in approved indications, receptor profiles, pharmacokinetics, and cytochrome P450 activity profile. Subtle differences exist in adverse effect profiles. All SSRIs have the potential to cause sexual dysfunction. Among the SSRIs, fluoxetine is felt to be the most activating.
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. Assess results of laboratory tests, therapeutic effectiveness, and adverse reactions at beginning of therapy and periodically with long-term use. Taper dosage slowly when discontinuing. Assess mental status for depression, suicidal ideation, anxiety, social functioning, mania, or panic attack. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Note: Strength expressed as base unless otherwise noted. [DSC] = Discontinued product
Capsule: 10 mg, 20 mg, 40 mg
Prozac®: 10 mg, 20 mg, 40 mg
Sarafem®: 10 mg [DSC], 20 mg
Selfemra™: 10 mg, 20 mg [contains soya lecithin]
Capsule, delayed release, enteric coated pellets:
Prozac® Weekly™: 90 mg
Solution, oral: 20 mg/5 mL (5 mL, 120 mL) [contains ethanol 0.23% and benzoic acid; mint flavor]
Prozac®: 20 mg/5 mL (120 mL) [contains ethanol 0.23% and benzoic acid; mint flavor]
Tablet: 10 mg, 20 mg
Prozac® [scored]: 10 mg [DSC]
Pricing: U.S. (www.drugstore.com)
Capsule, delayed release (Prozac Weekly)
90 mg (4): $121.81
Capsules (Fluoxetine HCl)
10 mg (30): $24.99
20 mg (30): $14.99
40 mg (30): $40.99
Capsules (Prozac)
10 mg (30): $166.26
20 mg (30): $151.93
40 mg (30): $325.23
Capsules (Selfemra)
10 mg (28): $25.00
20 mg (28): $27.99
Solution (Fluoxetine HCl)
20 mg/5 mL (120): $72.98
Solution (Prozac)
20 mg/5 mL (120): $252.64
Tablets (Fluoxetine HCl)
10 mg (30): $13.99
20 mg (30): $25.99
Tablets (Prozac)
10 mg (30): $122.17
Tablets (Sarafem)
10 mg (7): $49.99
20 mg (7): $49.99
Extemporaneously Prepared
A 20 mg capsule may be mixed with 4 oz of water, apple juice, or Gatorade® to provide a solution that is stable for 14 days under refrigeration.
References
American Academy of Pediatrics Committee on Drugs, “The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
American College of Obstetricians and Gynecologists, "ACOG Practice Bulletin No. 87 November 2007: Use of Psychiatric Medications During Pregnancy and Lactation" Obstet Gynecol, 2007, 110(5):1179-98.
Black B and Uhde TW, “Treatment of Elective Mutism With Fluoxetine: A Double Blind, Placebo-Controlled Study,” J Am Acad Child Adolesc Psychiatry, 1994, 33(7):1000-6.
Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.
Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al, “Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn,” N Engl J Med, 2006, 354(6):579-87.
Dummit ES 3rd, Klein RG, Tancer NK, et al, “Fluoxetine Treatment of Children With Selective Mutism: An Open Trial,” J Am Acad Child Adolesc Psychiatry, 1996, 35(5):615-21.
Emslie GJ, Rush AJ, Weinberg WA, et al, “A Double-Blind, Randomized, Placebo-Controlled Trial of Fluoxetine in Children and Adolescents With Depression,” Arch Gen Psychiatry, 1997, 54(11):1031-7.
Gonzalez-Rothi RJ, Zander DS, and Ros PR, “Fluoxetine Hydrochloride (Prozac®)-Induced Pulmonary Disease,” Chest, 1995, 107(6):1763-5.
Horton RC and Bonser RS, “Interaction Between Cyclosporin and Fluoxetine,” BMJ, 1995, 311(7002):422.
Jackson C, Carson W, Markowitz J, et al, “SIADH Associated With Fluoxetine and Sertraline Therapy,” Am J Psychiatry, 1995, 152(5):809-10.
Jennison TA, Brown P, Crossett J, et al, “A High-Performance Liquid Chromatographic Method for Quantitating Bupropion in Human Plasma or Serum,” J Anal Toxicol, 1995, 19(2):69-72.
Kingsbury SJ and Puckett KM, “Effects of Fluoxetine on Serum Clozapine Levels,” Am J Psychiatry, 1995, 152(3):473-4.
Kurlan R, Como PG, Deeley C, et al, “A Pilot Controlled Study of Fluoxetine for Obsessive-Compulsive Symptoms in Children With Tourette's Syndrome,” Clin Neuropharmacol, 1993, 16(2):167-72.
McKenzie LJ and Risch SC, “Fibrocystic Breast Disease Following Treatment With Selective Serotonin Reuptake Inhibitors,” Am J Psychiatry, 1995, 152(3):471.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Murthy R, Newton K, and Qureshi J, “The Association of Fluoxetine With Seizures,” J Psychopharmacol (Oxf), 1994, 8(3):187-8.
Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.
Rabins PV, Blacker D, Rovner BW, et al, “Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias,” October, 2007. Available at http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm
Reilly JG, Ayis SA, Ferrier IN, et al, “QTc-Interval Abnormalities and Psychotropic Drug Therapy in Psychiatric Patients,” Lancet, 2000, 355(9209):1048-52.
Riddle MA, Hardin MT, King R, et al, “Fluoxetine Treatment of Children and Adolescents With Tourette's and Obsessive-Compulsive Disorders: Preliminary Clinical Experience,” J Am Acad Child Adolesc Psychiatry, 1990, 29(1):45-8.
Riddle MA, Scahill L, King RA, et al, “Double-Blind, Crossover Trial of Fluoxetine and Placebo in Children and Adolescents With Obsessive-Compulsive Disorder,” J Am Acad Child Adolesc Psychiatry, 1992, 31(6):1062-9.
Sternbach H, “Fluoxetine-Clomipramine Interaction,” J Clin Psychiatry, 1995, 56(4):171-2.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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