fluoxetine

Absorption: Well absorbed after oral administration.

Distribution: Crosses the blood-brain barrier.

Protein Binding: 94.5%.

Metabolism/Excretion: Converted by the liver to norfluoxetine (primarily by the CYP2D6 isoenzyme), another antidepressant compound; the CYP2D6 enzyme system exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ fluoxetine concentrations and an ↑ risk of adverse effects). Fluoxetine and norfluoxetine are mostly metabolized by the liver; 12% excreted by kidneys as unchanged fluoxetine, 7% as unchanged norfluoxetine.

Half-Life: 1–3 days (norfluoxetine 5–7 days).

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	1–4 wk	unknown	2 wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);
Concurrent use of pimozide;
Concurrent use of thioridazine (fluoxetine should be discontinued ≥5 wk before thioridazine therapy is initiated).

Use Cautiously in:

History of seizures;
Debilitated patients (↑ risk of seizures);
Diabetes mellitus;
Patients with concurrent chronic illness or multiple drug therapy (dose adjustments may be necessary);
Hepatic impairment (↓ doses/↑ dosing interval may be necessary);
May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children;
Congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, concurrent use of QT interval prolonging drugs, hypokalemia, hypomagnesemia, recent MI, uncompensated HF, or bradycardia;
Angle-closure glaucoma;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk. Use during 1st trimester may ↑ risk of cardiovascular malformations in infant. Use during 3rd trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization and respiratory and nutritional support. Use may also be associated with persistent pulmonary hypertension in newborn. May cause sedation in infant;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; children <7 yr (safety and effectiveness not established);
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion and/or hyponatremia in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or ↑ dose.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, palpitations, QT interval prolongation, TORSADES DE POINTES

Derm: ↑sweating, pruritus, erythema nodosum, flushing, rash

EENT: mydriasis, stuffy nose, visual disturbances

Endo: SIADH, dysmenorrhea, hot flush

F and E: hyponatremia

GI: diarrhea, abdominal pain, abnormal taste, anorexia, constipation, dry mouth, dyspepsia, nausea, vomiting, weight loss

GU: ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction, urinary frequency

Hemat: BLEEDING

MS: arthralgia, back pain, myalgia

Neuro: anxiety, drowsiness, headache, insomnia, nervousness, tremor, abnormal dreams, dizziness, fatigue, hypomania, mania, NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, weakness

Resp: cough

Misc: fever, flu-like syndrome, hypersensitivity reactions, SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Discontinue use of MAO inhibitors for 14 days before fluoxetine therapy; combined therapy may result in confusion, agitation, seizures, hypertension, and hyperpyrexia (serotonin syndrome). Fluoxetine should be discontinued for ≥5 wk before MAO inhibitor therapy is initiated.
MAO-inhibitor-like drugs, such as linezolid or methylene blue may ↑ risk of serotonin syndrome; concurrent use contraindicated. Do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving fluoxetine, immediately discontinue fluoxetine and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first; may resume fluoxetine therapy 24 hr after last dose of linezolid or methylene blue.
Pimozide may ↑ risk of QT interval prolongation; concurrent use contraindicated.
May ↑ levels of thioridazine and risk of QT interval prolongation; concurrent use contraindicated. Fluoxetine should be discontinued for ≥5 wk before thioridazine is initiated.
QT interval prolonging drugs may ↑ the risk of QT interval prolongation with arrhythmias; avoid concurrent use.
Ritonavir and efavirenz may ↑ the risk of developing the serotonin syndrome. For concurrent use with ritonavir, ↓ fluoxetine dose by 70%; if initiating fluoxetine, start with 10 mg/day dose.
May ↑ levels and risk of toxicity of alprazolam; ↓ alprazolam dose by 50%.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans, ↑ risk of serotonin syndrome.
↑CNS depression with alcohol, antihistamines, other antidepressants, opioid analgesics, or sedative/hypnotics.
↑risk of side effects and adverse reactions with other antidepressants, risperidone, or phenothiazines.
May ↑ levels and risk of toxicity of carbamazepine, clozapine, digoxin, haloperidol, phenytoin, lithium, or warfarin.
May ↓ the effects of buspirone.
Cyproheptadine may ↓ or reverse effects of fluoxetine.
May ↑ sensitivity to adrenergics and ↑ the risk of serotonin syndrome.
↑risk of bleeding with NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, dabigatran, apixaban, edoxaban, rivaroxaban, or warfarin.

Drug-Natural Products:

↑risk of serotonin syndrome with St. John’s wort and SAMe.

Route/Dosage ⬆ ⬇

Depression

PO (Adults ): 20 mg once daily in the morning. After several wk, may ↑ by 20 mg/day at weekly intervals. Doses >20 mg/day should be given in 2 divided doses, in the morning and at noon (not to exceed 80 mg/day). Patients who have been stabilized on the 20 mg/day dose may be switched over to delayed-release capsules at dose of 90 mg once weekly, initiated 7 days after the last 20-mg dose.
PO Geriatric Patients ): 10 mg once daily in the morning initially; may be ↑ (not to exceed 60 mg/day).
PO (Children 7–17 yr): Adolescents and higher weight children: 10 mg once daily; may ↑ after 2 wk to 20 mg once daily; additional dosage ↑ may be made after several more wk (range: 20–60 mg/day); Lower-weight children: 10 mg once daily initially; may ↑ after several more wk (range: 20–30 mg/day).

Obsessive Compulsive Disorder

PO (Adults ): 20 mg once daily in the morning. After several wk, may ↑ by 20 mg/day at weekly intervals. Doses >20 mg/day should be given in 2 divided doses, in the morning and at noon (not to exceed 80 mg/day). Patients who have been stabilized on the 20 mg/day dose may be switched over to delayed-release capsules at dose of 90 mg once weekly, initiated 7 days after the last 20-mg dose.
PO (Children 7–17 yr): Adolescents and higher weight children: 10 mg once daily; may ↑ after 2 wk to 20 mg once daily; additional dosage ↑ may be made after several more wk (range: 20–60 mg/day); Lower-weight children: 10 mg once daily initially; may ↑ after several more wk (range: 20–30 mg/day).

Panic Disorder

PO (Adults ): 10 mg once daily initially; may ↑ after 1 wk to 20 mg once daily (may ↑ as needed/tolerated up to 60 mg/day).

Bulimia Nervosa

PO (Adults ): 60 mg once daily.

Premenstrual Dysphoric Disorder

PO (Adults ): 20 mg once daily (not to exceed 80 mg/day) or 20 mg once daily starting 14 days prior to expected onset on menses, continued through 1st full day of menstruation, repeated with each cycle.

Depressive Disorders Associated with Bipolar I Disorder

PO (Adults ): 20 mg once daily with olanzapine 5 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg/day and olanzapine dose up to 12.5 mg/day.
PO (Children 10–17 yr): 20 mg once daily with olanzapine 2.5 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg once daily and olanzapine dose up to 12 mg/day.

Treatment-Resistant Depression

PO (Adults ): 20 mg once daily with olanzapine 5 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg once daily and olanzapine dose up to 20 mg/day.

Availability ⬆ ⬇

(Generic available)

Tablets: 10 mg; 20 mg; 60 mg
Capsules: 10 mg; 20 mg; 40 mg; 60 mg
Delayed-release capsules: 90 mg
Oral solutionmint flavor: 20 mg/5 mL
In combination with: olanzapine (generic).

Assessment ⬆ ⬇

Monitor mood changes to determine effectiveness.
- Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be ↑ in children, adolescents, and adults ≤24 yr. After starting therapy, children, adolescents, and young adults should be seen by health care provider face-to-face at least weekly for 4 wk, then every other wk for next 4 wk, then at 12 wk, and then on advice of health care provider thereafter.
- Monitor appetite and nutritional intake. Weigh weekly and adjust diet as tolerated to support nutritional status.
- Assess for hypersensitivity reaction (urticaria, fever, arthralgia, edema, carpal tunnel syndrome, rash, hives, lymphadenopathy, respiratory distress). If rash or other symptoms occur, discontinue fluoxetine and treat as indicated.
Assess baseline sexual function and for changes in sexual function during therapy.
Monitor for neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, arrhythmias, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). If signs or symptoms occur, discontinue fluoxetine and treat as indicated.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans). If signs and symptoms occur, discontinue fluoxetine and any concurrent serotonergic drugs; treat as indicated.
OCD: Assess for frequency of obsessive-compulsive behaviors. Note degree to which these thoughts and behaviors interfere with daily functioning.
Bulimia Nervosa: Assess frequency of binge eating and vomiting during therapy.

Lab Test Considerations:

Monitor CBC and differential periodically during therapy and clotting times as clinically indicated. May ↑ risk of bleeding.
- Proteinuria and ↑ AST may occur during hypersensitivity reaction.
- May ↑alkaline phosphatase, ALT, BUN, and CK; may cause hyperuricemia, hypocalcemia, hypoglycemia, hyperglycemia, and hyponatremia.
- May cause hypoglycemia in patient with diabetes.

Implementation ⬆ ⬇

Do not confuse fluoxetine with duloxetine or paroxetine. Do not confuse Prozac with Prilosec, Prograf, or Provera.
PO: Administer as a single dose in the morning. Some patients may require ↑ amounts, with a 2nd dose at noon.
- May be administered with food to minimize GI irritation. DNC: Do not open, dissolve, chew, or crush delayed-release capsules.
- Delayed release capsules may be started after last dose of PROzac 20 mg. May ↑ dose after several wk if no clinically significant improvement.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Instruct patient to take missed dose as soon as remembered unless almost time for next dose; then omit and return to regular schedule. Do not double doses or discontinue without consulting health care provider; discontinuation may cause anxiety, insomnia, or nervousness.
May cause drowsiness, dizziness, impaired judgment, and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response is known.
Advise patient, family, and caregivers to watch for suicidality, especially during early therapy or dose changes. Notify health care provider immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
Advise patient and caregivers to immediately notify health care provider if symptoms of serotonin syndrome occur.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications. Advise patient to avoid taking other CNS depressants, including opioids, or alcohol. Advise patient that concurrent use of aspirin, NSAIDs, or anticoagulants may ↑ bleeding risk.
Caution patient to change positions slowly to minimize dizziness.
Inform patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may minimize dry mouth. If dry mouth persists for >2 wk, consult health care provider regarding use of saliva substitute.
Caution patient to wear protective clothing and use sunscreen to prevent photosensitivity reactions.
Advise patient to notify health care provider if symptoms of hypersensitivity reaction occur or if headache, nausea, anorexia, anxiety, or insomnia persist.
Inform patient that fluoxetine may cause symptoms of sexual dysfunction. Advise patient to notify health care provider if ejaculatory delay or failure, ↓ libido, erectile dysfunction, or delayed/absent orgasm occur.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Use during 1st trimester may ↑ risk of cardiovascular malformations in infant. Monitor infants exposed to fluoxetine during 3rd trimester for respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. May ↑ risk of postpartum hemorrhage. Monitor infants exposed to fluoxetine via breast milk for agitation, irritability, poor feeding, and poor weight gain. Inform patient of pregnancy exposure registry. Register patient in the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.
Emphasize the importance of follow-up exams to monitor progress.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇