Fluoxetine

Daily Prozac: major depressive disorder (MDD), OCD, moderate-to-severe bulimia nervosa, and panic disorder with or without agoraphobia. Pediatric efficacy is established for MDD at ages 8–18 and OCD at ages 7–17; other indications are not generalized to children.

The 90 mg delayed-release product is a distinct once-weekly MDD continuation regimen after response to daily therapy.

With olanzapine, fluoxetine is labeled for acute bipolar I depressive episodes (adults and ages 10–17) and adult treatment-resistant depression after two adequate antidepressant trials in the current episode. Monotherapy is not indicated for these combination uses; consult both component/combination labels.

• Doses above 20 mg/day may be given once in the morning or in morning/noon doses. Food is optional. Full MDD benefit may take ≥4 weeks; reassess maintenance need.

MDD ages 8–18: start 10 or 20 mg/day; if starting at 10 mg, increase to 20 mg after 1 week. Lower-weight children may use 10 mg as both starting and target dose, with a later increase after several weeks if needed. Supporting trials used 10–20 mg/day.

OCD ages 7–17: start 10 mg/day. Higher-weight children/adolescents may increase to 20 mg after 2 weeks; usual range 20–60 mg/day with later increases after several weeks. Lower-weight children: consider later increases; usual range 20–30 mg/day, with very limited experience above 20 mg and none above 60 mg.

For adult MDD continuation after satisfactory daily treatment response, start the once-weekly capsule 7 days after the last daily 20 mg dose. Weekly and daily regimens are not interchangeable pill-for-pill; equivalence in maintaining response has not been established. If response is not maintained, the clinician may return to daily therapy. This is not a 90 mg daily regimen.

Bipolar I depression: adult initial oral combination generally 5 mg olanzapine plus 20 mg fluoxetine each evening; ages 10–17 generally 2.5 mg plus 20 mg. Adult treatment-resistant depression generally starts 5 mg plus 20 mg each evening. These are component regimens; fixed-dose Symbyax correspondence and titration require its separate label.

Use a lower or less frequent dose with hepatic impairment; consider the same in older adults or medically complex patients. A renal reduction is not routinely necessary in the cited label, including its small dialysis study. Individualize rather than assuming identical exposure in every patient.

Wait at least 14 days after stopping a psychiatric MAOI before starting fluoxetine, and at least 5 weeks after stopping fluoxetine before starting a psychiatric MAOI. Do not start fluoxetine during linezolid or IV methylene blue treatment. Urgent use of these drugs requires a prescriber-managed interruption and monitoring protocol from section 2.10.

Taper when possible and monitor discontinuation symptoms; long elimination does not eliminate withdrawal risk.

Psychiatric MAOIs during treatment or within 5 weeks after fluoxetine; fluoxetine within 14 days after an MAOI. Initiation with linezolid or IV methylene blue is contraindicated. Pimozide and thioridazine are contraindicated because of QT and metabolic interactions. Thioridazine must also be avoided for at least 5 weeks after fluoxetine. Olanzapine combination therapy requires the separate combination contraindications.

Short-term antidepressant studies found increased suicidal thoughts/behaviors in children, adolescents, and young adults; all ages require monitoring for clinical worsening and emerging suicidality. Families/caregivers should promptly communicate concerning changes. Pediatric approval depends on the condition and age.

Reported common trial effects include nausea, diarrhea, dry mouth, insomnia, anxiety/nervousness, somnolence, dizziness, tremor, sweating, decreased appetite, and sexual dysfunction. Serious effects include the syndromes described above; trial rates vary by indication and do not establish an individual risk.

Overdose can cause delayed seizures, coma, QT/QRS changes, arrhythmia, and serotonin toxicity. Obtain poison-center or emergency guidance promptly; do not wait for symptoms. U.S. Poison Control: 1-800-222-1222; call 911 for collapse, seizure, impaired breathing, or inability to awaken.

• ECT has rare reports of prolonged seizures with fluoxetine; coordinate with the treating team. Consult the complete interaction sections for other medicines and protein-binding effects.

Epidemiologic data have not established increased major birth-defect or miscarriage risk, but observational data do not prove absence of risk. Late SSRI exposure is associated with neonatal adaptation problems and possible persistent pulmonary hypertension; exposure near delivery has been associated with postpartum bleeding. Balance these concerns with relapse and untreated depression risks.

Fluoxetine and norfluoxetine enter milk. Reports include infant irritability/agitation, poor feeding and poor weight gain; monitor the infant and individualize maternal treatment with the clinician.

MDD approval begins at age 8 and OCD at age 7; monitor mood, mania and height/weight during pediatric treatment. Adult doses for bulimia/panic or weekly maintenance are not pediatric instructions. Older adults may need lower/less frequent dosing and have greater hyponatremia risk.

Cirrhosis slows parent-drug and active-metabolite clearance; use a lower or less frequent regimen. Routine renal dose reduction is not required by the cited label, but comorbidity and interacting drugs still require individual assessment.

Antidepressant action is presumed to involve CNS serotonin uptake inhibition; the complete therapeutic mechanism is unknown.

Metabolism

Extensive hepatic metabolism, including CYP2D6, to active norfluoxetine and other metabolites; inhibits CYP2D6.

Half-life

Fluoxetine: 1–3 days after acute dosing, 4–6 days after chronic dosing. Norfluoxetine: 4–16 days.

Elimination

Predominantly hepatic metabolism followed by renal elimination of inactive metabolites.

Accumulation

Active species persist for weeks; changes in dose are not fully reflected in concentrations for several weeks.

• Assess response, suicidal thinking, behavioral activation, sleep and mania during early therapy and dose changes.
• Monitor weight/appetite and pediatric height/weight; ask about sexual effects.
• Check sodium when clinically indicated by symptoms or risk; ECG/electrolyte review in patients at QT risk. Monitor glucose in diabetes and interacting drug levels/INR as appropriate.

• Take exactly as prescribed, including the daily-versus-weekly schedule. Do not double doses or change treatment independently.
• Tell clinicians about all medicines/supplements and recent fluoxetine use, even weeks after stopping.
• Read the Medication Guide each refill; report worsening mood or unusual behavior promptly and seek immediate help for suicidal intent.
• Avoid hazardous tasks until alertness effects are known. Arrange a taper with the prescriber rather than stopping suddenly.

Dosage form / strength

Daily oral capsule · 20 mg fluoxetine equivalent

Appearance / imprint

Opaque green cap, yellow body · DISTA 3105 / Prozac 20 mg

Example NDC

0777-3105-30 · 30 capsules

Prozac daily capsules

10, 20 and 40 mg.

Selected delayed-release weekly capsule

90 mg · RDY / 284; brown cap, white body.

Additional products

Other tablets, oral solution and olanzapine combinations require their exact labels.

Prozac capsules: controlled room temperature 15–30°C; protect from light. Selected weekly capsules: 20–25°C. Retain product packaging and keep medicines out of children’s reach.