No

Antidepressant, Selective Serotonin Reuptake Inhibitor

Treatment of major depression; treatment of binge-eating and vomiting in patients with moderate-to-severe bulimia nervosa; obsessive-compulsive disorder

C

Hypersensitivity to this agent. Use of MAO inhibitors within prior 14 days; a MAO inhibitor should not be initiated until 5 weeks after the discontinuation of fluoxetine.

Potential for severe reaction when used with MAO inhibitors - serotonin syndrome (hyperthermia, muscular rigidity, mental status changes/agitation, autonomic instability) may occur. Fluoxetine use has been associated with occurrences of significant rash and allergic events, including vasculitis, anaphylactoid reactions, and pulmonary inflammatory disease. May precipitate a shift to mania or hypomania in patients with bipolar disease. May cause insomnia, anxiety, nervousness or anorexia. Use with caution in patients where weight loss is undesirable. May impair cognitive or motor performance - caution operating hazardous machinery or driving. Use caution in patients with depression, particularly if suicidal risk may be present. Use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in patients with hepatic or renal dysfunction and in elderly patients. May cause hyponatremia/SIADH. May increase the risks associated with electroconvulsive treatment. Use with caution in patients at risk of bleeding or receiving concurrent anticoagulant therapy - may cause impairment in platelet function. May alter glycemic control in patients with diabetes. Due to the long half-life of fluoxetine and its metabolites, the effects and interactions noted may persist for prolonged periods following discontinuation. May cause or exacerbate sexual dysfunction.

Predominant adverse effects are CNS and GI

Central nervous system: Headache, nervousness, insomnia, anxiety, somnolence

Gastrointestinal: Nausea, diarrhea, xerostomia, anorexia

Neuromuscular & skeletal: Weakness

1% to 10%:

Cardiovascular: Vasodilation, palpitation, hypertension

Central nervous system: Amnesia, confusion, emotional lability, sleep disorder, dizziness, agitation, yawning

Dermatologic: Rash, pruritus

Endocrine & metabolic: SIADH, hypoglycemia, hyponatremia (elderly or volume-depleted patients)

Gastrointestinal: Dyspepsia, increased appetite, constipation, vomiting, flatulence, weight loss, weight gain

Genitourinary: Sexual dysfunction, urinary frequency

Neuromuscular & skeletal: Tremor

Ocular: Abnormal vision

Respiratory: Pharyngitis

Miscellaneous: Diaphoresis, fever, flu syndrome

<1%: Extrapyramidal reactions (rare), euphoria, hallucinations, hostility, dehydration, edema, gout, hypercholesteremia, hypokalemia, arthritis, bone pain, bursitis, leg cramps, angina, CHF, arrhythmia, hypotension, myocardial infarction, syncope, tachycardia, aphthous stomatitis, cholelithiasis, colitis, dysphagia, gastritis, glossitis, hypothyroidism, asthma, epistaxis, hiccup, hyperventilation, anemia, ecchymosis, albuminuria, amenorrhea, visual disturbances, anaphylactoid reactions, allergies, suicidal ideation, erythema nodosum

Symptoms of overdose include ataxia, sedation, and coma; respiratory depression may occur, especially with coingestion of alcohol or other drugs; seizures very rarely occur

CYP2D6 enzyme substrate (minor), CYP3A3/4 enzyme substrate; CYP2C9 enzyme inducer; CYP1A2, 2C19, 2D6, and 3A3/4 enzyme inhibitor

Fluoxetine inhibits the metabolism of tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline) resulting is elevated serum levels; if combination is warranted, a low dose of TCA (10-25 mg/day) should be utilized

Fluoxetine may cause hyponatremia; additive hyponatremic effects may be seen with combined use of a loop diuretic (bumetanide, furosemide, torsemide); monitor for hyponatremia

Fluoxetine inhibits the reuptake of serotonin; combined use with a serotonin agonist (buspirone) may cause serotonin syndrome

Fluoxetine may inhibit the metabolism of carbamazepine resulting in increased carbamazepine levels and toxicity; monitor for altered CBZ response

Cyproheptadine, a serotonin antagonist may inhibit the effects of serotonin reuptake inhibitors (fluoxetine); monitor for altered antidepressant response

Fluoxetine inhibits the metabolism of dextromethorphan; visual hallucinations occurred in a patient receiving this combination; monitor for serotonin syndrome

Fluoxetine may inhibit the metabolism of haloperidol and cause extrapyramidal symptoms (EPS); monitor patients for EPS if combination is utilized

Fluoxetine should not be used with nonselective MAOIs (isocarboxazid, phenelzine). Fatal reactions have been reported. Wait 5 weeks after stopping fluoxetine before starting an MAOI and 2 weeks after stopping an MAOI before starting fluoxetine.

Patients receiving fluoxetine and lithium have developed neurotoxicity. If combination is used, monitor for neurotoxicity

Fluoxetine may inhibit the metabolism of metoprolol and propranolol resulting in cardiac toxicity; monitor for bradycardia, hypotension, and heart failure if combination is used

Fluoxetine inhibits the reuptake of serotonin; combined use with other drugs which inhibit the reuptake (nefazodone, sibutramine) may cause serotonin syndrome. Monitor patient for altered response with nefazodone; avoid sibutramine combination.

Fluoxetine inhibits the metabolism of phenytoin and may result in phenytoin toxicity; monitor for phenytoin toxicity (ataxia, confusion, dizziness, nystagmus, involuntary muscle movement)

Fluoxetine has been reported to cause mania or hypertension when combined with selegiline; this combination is best avoided

Fluoxetine may inhibit the metabolism of lovastatin and simvastatin resulting in myositis and rhabdomyolysis; these combinations are best avoided

Fluoxetine combined with tramadol (serotonergic effects) may cause serotonin syndrome; monitor

Fluoxetine may inhibit the metabolism of trazodone resulting in increased toxicity; monitor

Fluoxetine inhibits the reuptake of serotonin; combination with tryptophan, a serotonin precursor, may cause agitation and restlessness; this combination is best avoided

Fluoxetine may alter the hypoprothombinemic response to warfarin; monitor

All dosage forms should be stored at controlled room temperature (15°C to 30°C or 50°F to 86°F); oral liquid should be dispensed in a light-resistant container

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

Onset of effect: >2-4 weeks for therapeutic effects

Peak antidepressant effect: After >4 weeks

Absorption: Oral: Well absorbed

Metabolism: To norfluoxetine (active)

Half-life: Adults: 2-3 days; due to long half-life, resolution of adverse reactions after discontinuation may be slow

Time to peak serum concentration: Within 4-8 hours

Elimination: In urine as fluoxetine (2.5% to 5%) and norfluoxetine (10%)

Oral:

Adults: 20 mg/day in the morning; may increase after several weeks by 20 mg/day increments; maximum: 80 mg/day; doses >20 mg should be divided into morning and noon doses

Usual dosage range:

20-40 mg/day for depression and 40-80 mg for OCD

20-60 mg/day for obesity

60-80 mg/day for bulimia nervosa

Note: Lower doses of 5 mg/day have been used for initial treatment

Elderly: 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

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

Alcohol: Avoid use

Therapeutic levels have not been well established

Toxic: Fluoxetine plus norfluoxetine: >2000 ng/mL

albumin in urine

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

>10% of patients experience dry mouth

Take exactly as directed (do not increase dose or frequency); may take 2-3 weeks to achieve desired results; may cause physical and/or psychological dependence. Take once-a-day dose in the morning to reduce incidence of insomnia. Avoid excessive 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, or dietary fruit and 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 diabetic, monitor serum glucose closely (may cause hypoglycemia). Report persistent CNS effects (nervousness, restlessness, insomnia, anxiety, excitation, headache, sedation); rash or skin irritation; muscle cramping, tremors, or change in gait; respiratory depression or difficulty breathing; or worsening of condition. Breast-feeding precautions: Breast-feeding is not recommended.

Offer patient sugarless hard candy for dry mouth

Capsule, as hydrochloride: 10 mg, 20 mg, 40 mg

Liquid, as hydrochloride (mint flavor): 20 mg/5 mL (120 mL)

Tablet, as hydrochloride: 10 mg, 20 mg

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

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