PROZAC
Clinical safety rating
cautionComprehensive 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 |
| Molecular Weight | 309.33 |
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 | Limited human data suggest possible risk of cardiovascular malformations, particularly with first trimester exposure. Use only if potential benefit outweighs risk. |
| 2nd trimester | Limited data; no clear evidence of teratogenicity. Monitor for maternal mental health and adjust dose if needed. |
| 3rd trimester | Late third trimester exposure may increase risk for persistent pulmonary hypertension of the newborn (PPHN) and poor neonatal adaptation syndrome (irritability, feeding difficulties). Taper if possible near term. |
Clinical note
Comprehensive clinical and safety monograph for PROZAC (PROZAC).
| Placental transfer | Fluoxetine crosses the placenta; cord blood concentrations are approximately 50-80% of maternal serum levels. Active metabolite norfluoxetine accumulates in the fetus. |
| Breastfeeding | Fluoxetine and its active metabolite norfluoxetine are excreted into breast milk with infant serum levels detectable in some cases. Irritability, colic, and poor feeding have been reported. Benefit of breastfeeding should be weighed against potential risks, especially for preterm or compromised infants. |
| Lactation Rating | L3 - Moderately Safe |
| 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. |
| 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. |
■ 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 |
Concomitant use with MAOIs or within 14 days of discontinuing MAOIsConcomitant use with pimozideConcomitant use with thioridazineKnown hypersensitivity to fluoxetine or any component of the formulation
| Precautions | Suicidality in pediatric patients, Activation of mania/hypomania, QT interval prolongation, Serotonin syndrome, Discontinuation syndrome, Bleeding risk (with NSAIDs/aspirin) |
| Food/Dietary | Avoid grapefruit juice as it inhibits CYP3A4 and may increase fluoxetine levels. Alcohol may potentiate CNS depression; advise minimal or no alcohol use. No other significant food interactions. |
| Clinical Pearls | Commonly used in bulimia nervosa (60 mg/day) and premenstrual dysphoric disorder (20 mg/day continuously or 20 mg/day only during luteal phase). Requires 4-6 weeks for full therapeutic effect. Abrupt discontinuation may cause withdrawal symptoms; taper over 2-4 weeks. Risk of serotonin syndrome when combined with MAOIs, other serotonergic drugs, or linezolid. Lower starting dose (10 mg) in hepatic impairment or elderly. Suicidality warning especially in children, adolescents, and young adults. |
| Patient Advice | Take exactly as prescribed, usually once daily in the morning to minimize insomnia. · It may take 4-6 weeks to feel full benefit; do not stop abruptly. · Do not take with MAOIs or within 14 days of stopping MAOIs. · Report any suicidal thoughts, especially during the first few weeks. · Avoid alcohol and grapefruit juice as they may increase side effects. · If you miss a dose, skip it; do not double the next dose. |
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