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 at least 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;
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 first trimester may risk of cardiovascular malformations in infant. Use during third trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, 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: Risk of suicidal ideation or attempt may be greater in children or adolescents;
Pedi: 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, 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 at least 5 wk before MAO inhibitor therapy is initiated.
Concurrent use with 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)
Concurrent use with pimozide may ↑ risk of QT interval prolongation.
↑levels of thioridazine may ↑ risk of QT interval prolongation (concurrent use contraindicated; fluoxetine should be discontinued for at least 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.
↓metabolism and ↑ effects of alprazolam (decrease 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 ↑ effectiveness/risk of toxicity from 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 increase the risk of serotonin syndrome.
May alter the activity of other drugs that are highly bound to plasma proteins.
↑risk of serotonin syndrome with 5HT1 agonists.
↑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 ⬆ ⬇

PO (Adults ): Depression or OCD: 20 mg/day in the morning. After several wk, may ↑ by 20 mg/day at weekly intervals. Doses greater than 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. Panic disorder: 10 mg/day initially, may ↑ after 1 wk to 20 mg/day (usual dose is 20 mg, but may be ↑ as needed/tolerated up to 60 mg/day). Bulimia nervosa: 60 mg/day (may need to titrate up to dosage over several days). PMDD: 20 mg/day (not to exceed 80 mg/day) or 20 mg/day starting 14 days prior to expected onset on menses, continued through first full day of menstruation, repeated with each cycle. Depressive episodes associated with bipolar I disorder: 20 mg/day 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; Treatment-resistant depression: 20 mg/day with olanzapine 5 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg/day and olanzapine dose up to 20 mg/day.
PO Geriatric Patients ): Depression: 10 mg/day in the morning initially, may be ↑ (not to exceed 60 mg/day).
PO (Children 7–17 yr): Depression or OCD (adolescents and higher weight children): 10 mg/day may be ↑ after 2 wk to 20 mg/day; additional increases may be made after several more wk (range 20–60 mg/day); Depression or OCD (lower-weight children): 10 mg/day initially, may be ↑ after several more wk (range 20–30 mg/day).
PO (Children 10–17 yr): Depressive episodes associated with bipolar I disorder: 20 mg/day with olanzapine 2.5 mg/day (both given in evening); may ↑ fluoxetine dose up to 50 mg/day and olanzapine dose up to 12 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 (Symbyax; see Appendix [not included in this PDA edition]).

Assessment ⬆ ⬇

Monitor mood changes. Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
- Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care professional thereafter.
- Monitor appetite and nutritional intake. Weigh weekly. Notify health care professional of continued weight loss. Adjust diet as tolerated to support nutritional status.
- Assess for sensitivity reaction (urticaria, fever, arthralgia, edema, carpal tunnel syndrome, rash, hives, lymphadenopathy, respiratory distress) and notify health care professional if present; symptoms usually resolve by stopping fluoxetine but may require administration of antihistamines or corticosteroids.
Assess sexual function before starting fluoxetine. Assess for changes in sexual function during treatment, including timing of onset; patient may not report.
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, arrhythmias, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Report immediately.
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).
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.
PMDD: Monitor mood prior to and periodically during therapy.

Lab Test Considerations:

Monitor CBC and differential periodically during therapy. Notify health care professional if leukopenia, anemia, thrombocytopenia, or increased bleeding time occurs.
- Proteinuria and mild ↑ in AST may occur during sensitivity reactions.
- May cause ↑ in serum alkaline phosphatase, ALT, BUN, and CK, as well as 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 increased amounts, in divided doses, 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. Dose may be increased after several wk if improvement not clinically significant.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take fluoxetine as directed. Take missed doses 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 professional; discontinuation may cause anxiety, insomnia, nervousness.
May cause drowsiness, dizziness, impaired judgment, and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to the drug is known.
Advise patient, family, and caregivers to watch for suicidality, especially during early therapy or dose changes. Notify health care professional 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, or if symptoms of serotonin syndrome occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Advise patient to avoid taking other CNS depressants, including opioids, or alcohol.
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 more than 2 wk, consult health care professional regarding use of saliva substitute.
Caution patient to wear protective clothing and use sunscreen to prevent photosensitivity reactions.
Advise patient to notify health care professional if symptoms of sensitivity reaction occur or if headache, nausea, anorexia, anxiety, or insomnia persists.
Inform patient that fluoxetine may cause symptoms of sexual dysfunction. In males, ejaculatory delay or failure, decreased libido, and erectile dysfunction may occur. In female patients, may result in decreased libido and delayed or absent orgasm. Advise patient to notify health care professional if symptoms occur.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Use during first 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 increase 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 that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Register patient by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at 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 ⬆ ⬇