PROZAC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROZAC (PROZAC).
Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity in the CNS by blocking the reuptake of serotonin into presynaptic neurons.
| Metabolism | Hepatic via CYP2D6, CYP2C9, CYP2C19, and CYP3A4; active metabolite norfluoxetine. |
| Excretion | Renal: ~80% (primarily as metabolites, <10% unchanged); fecal: ~15% |
| Half-life | Fluoxetine: 4-6 days; norfluoxetine: 4-16 days; extensive accumulation with chronic dosing, steady-state in 4-5 weeks |
| Protein binding | ~94.5% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 12-42 L/kg; extensive tissue binding, particularly in lungs and brain |
| Bioavailability | Oral: 60-80% due to first-pass metabolism; not administered parenterally |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; maximal at 6-8 weeks |
| Duration of Action | Active metabolite extends duration; effects persist for weeks after discontinuation due to long half-life |
20 mg orally once daily, initially; may increase to 40 mg once daily after several weeks; maximum 80 mg once daily.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: administer 50% of usual dose; GFR <10 mL/min: administer 50% of usual dose or use alternative; not removed by hemodialysis. |
| Liver impairment | Child-Pugh Class A: no dose adjustment needed; Child-Pugh Class B: reduce dose by 50% or use alternative; Child-Pugh Class C: contraindicated or use alternative with caution. |
| Pediatric use | Children 7-17 years: 10-20 mg orally once daily, initially; may increase to 20-40 mg once daily after ≥1 week; maximum 40 mg once daily. |
| Geriatric use | Consider starting dose of 10 mg orally once daily; may increase slowly to 20 mg once daily; maximum 40 mg once daily; monitor for hyponatremia and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROZAC (PROZAC).
| Breastfeeding | Fluoxetine and its active metabolite norfluoxetine are excreted into breast milk. Milk-to-plasma ratio for fluoxetine is approximately 0.29. Infant serum levels can reach up to 10% of maternal therapeutic levels, with norfluoxetine accumulating. Adverse effects reported include irritability, poor feeding, and colic. American Academy of Pediatrics considers fluoxetine as a drug with 'potentially significant' effects; caution is advised, and breastfeeding should be weighed against maternal need. |
| Teratogenic Risk | First trimester: Studies suggest a small increased risk of cardiovascular malformations, particularly ventricular septal defects, with relative risk approximately 1.5-1.7. Third trimester: Exposure is associated with risk of persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome (including irritability, respiratory distress, feeding difficulty). Second trimester: No specific major risks identified beyond general population baseline. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorder and other psychiatric disorders.
| Serious Effects |
["Hypersensitivity to fluoxetine","Concomitant use with MAOIs or within 14 days of MAOI discontinuation","Concomitant use with pimozide or thioridazine"]
| Precautions | ["Suicidality in pediatric patients","Activation of mania/hypomania","QT interval prolongation","Serotonin syndrome","Discontinuation syndrome","Bleeding risk (with NSAIDs/aspirin)"] |
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| Fetal Monitoring | Maternal monitoring: Serum fluoxetine levels if toxicity suspected; psychiatric evaluation for mood stability; blood pressure and weight monitoring. Fetal/neonatal monitoring: Fetal echocardiography if first-trimester exposure; neonatal observation for adaptation syndrome (48-72 hours) including respiratory effort, tone, feeding, and irritability; assessment for PPHN in newborns with respiratory distress. |
| Fertility Effects | Fluoxetine may cause reversible sexual dysfunction (delayed ejaculation, decreased libido, anorgasmia) in both men and women, which can impair fecundity. In animal studies, high doses did not significantly affect fertility. Human data show no clear evidence of irreversible infertility, but treatment may interfere with conception via sexual side effects. |