Clinical safety rating
safeFor completeness: fluoxetine is also used postpartum for postnatal depression. The main breastfeeding consideration is its long half-life (fluoxetine + norfluoxetine) leading to measurable infant serum concentrations. While not contraindicated, sertraline or paroxetine are preferred for breastfeeding mothers. Separate slug to capture postnatal searches.
Selective serotonin reuptake inhibitor (SSRI); inhibits serotonin reuptake in the synaptic cleft, potentiating serotonergic activity in the CNS.
| Metabolism | Hepatic via CYP2D6, CYP2C9, CYP3A4; active metabolite norfluoxetine. |
| Excretion | Renal (80% as metabolites, 10% as unchanged drug) and fecal (15%) |
| Half-life | Fluoxetine: 4-6 days (acute), 4-6 weeks (chronic); norfluoxetine: 4-16 days. Steady-state achieved after 2-4 weeks. |
| Protein binding | 94% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 12-43 L/kg; extensive tissue distribution including brain, breast milk. |
| Bioavailability | Oral: 95% (72% after first-pass); food may slightly decrease rate but not extent. |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; anxiety improvement may begin at 1-2 weeks. IV not available. |
| Duration of Action | Extended due to long half-life; therapeutic effect persists for weeks after discontinuation. Tapering recommended. |
| Molecular Weight | 309.33 |
20 mg orally once daily, initially; may increase after several weeks to a maximum of 80 mg/day. Administer in the morning.
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). For severe renal impairment (GFR <30 mL/min), use cautiously with a maximum dose of 40 mg/day. |
| Liver impairment | Child-Pugh Class A: 20 mg every other day; Class B: 20 mg every third day; Class C: avoid use or use 10 mg every third day with careful monitoring. |
| Pediatric use | Children (8-12 years): 10-20 mg orally once daily; adolescents (13-17 years): 20 mg orally once daily. Maximum 60 mg/day. Weight-based: 0.5-1.0 mg/kg/day, titrate to maximum 1.5 mg/kg/day. |
| Geriatric use | Initial dose 10 mg orally once daily; titrate slowly to a maximum of 40 mg/day due to increased half-life and risk of hyponatremia and QT prolongation. |
| 1st trimester | Increases risk of cardiac malformations, particularly ventricular septal defects (VSDs), with relative risk approximately 1.6-1.8. Risk of persistent pulmonary hypertension of the newborn (PPHN) increased ~2-fold. Consider alternative therapy if possible. |
| 2nd trimester | Limited direct teratogenic risk but may increase risk of preterm labor and low birth weight. Monitor for maternal depression exacerbation. |
| 3rd trimester | Risk of neonatal adaptation syndrome (irritability, feeding difficulties, respiratory distress) in 30% of neonates. Avoid or taper in late pregnancy to reduce severity. |
Clinical note
For completeness: fluoxetine is also used postpartum for postnatal depression. The main breastfeeding consideration is its long half-life (fluoxetine + norfluoxetine) leading to measurable infant serum concentrations. While not contraindicated, sertraline or paroxetine are preferred for breastfeeding mothers. Separate slug to capture postnatal searches.
| Placental transfer | High placental transfer, with cord-to-maternal plasma ratio approximately 0.7-0.9. Extensive passage due to lipophilicity and long half-life. |
| Breastfeeding | Fluoxetine and its active metabolite norfluoxetine are excreted into breast milk with high relative infant dose (RID) of 2-11%. Cases of infant serum concentrations reaching therapeutic levels, including one report of seizures. Monitor infant for drowsiness, irritability, and weight gain. Use only if benefits outweigh risks. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Exposure associated with a small increased risk of cardiovascular malformations, primarily ventricular septal defects (absolute risk ~2-3% vs 1% baseline). Second/third trimester: Persistent pulmonary hypertension of the newborn (PPHN) risk ~1.5-2 times baseline; risk of preterm birth and low birth weight. Late third trimester: Risk of poor neonatal adaptation syndrome (PNAS) including jitteriness, respiratory distress, feeding difficulties, and irritability. |
| Fetal Monitoring | Maternal: Monitor for mood stability, weight gain, blood pressure, and signs of serotonin syndrome or bleeding. Fetal/neonatal: Serial fetal growth ultrasound in third trimester due to risk of low birth weight; assess for PPHN at birth; monitor for PNAS symptoms for 48-72 hours postpartum including respiratory rate, feeding, and neurological status. |
| Fertility Effects | Animal studies suggest no major impact on fertility. In humans, SSRIs may cause reversible sexual dysfunction (delayed ejaculation, anorgasmia) which could affect fertility indirectly. No evidence of impaired conception rates; however, some studies indicate a potential for reduced ovarian reserve markers, but clinical significance is unclear. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Common Effects | Application site reactions burning irritation itching and redness |
| Serious Effects |
Hypersensitivity to fluoxetine or any componentConcurrent use with MAOIs or within 14 days of MAOI discontinuationConcurrent use with pimozideConcurrent use with thioridazine
| Precautions | Serotonin syndrome; risk of bleeding; activation of mania/hypomania; hyponatremia; discontinuation syndrome; QT prolongation (overdose). |
| Food/Dietary | No specific food interactions; avoid grapefruit juice as it may increase fluoxetine levels. Take with or without food; if GI upset occurs, take with food. |
| Clinical Pearls | Fluoxetine has a long half-life (4-6 days, norfluoxetine 4-16 days) resulting in steady-state after 2-4 weeks; use lower starting doses (10 mg daily) in postpartum women to minimize side effects; monitor for neonatal adaptation syndrome if used in third trimester; consider dose adjustment in hepatic impairment; avoid in breastfeeding unless benefit outweighs risk due to presence in breast milk. |
| Patient Advice | Take fluoxetine exactly as prescribed, typically once daily in the morning. · It may take 4 weeks or longer to feel full benefit; do not stop abruptly. · Common side effects include nausea, headache, insomnia, and sexual dysfunction. · Contact your doctor if you experience rash, unusual bleeding, or suicidal thoughts. · Avoid alcohol while taking this medication. · Do not breastfeed without discussing risks with your healthcare provider. |
Loading safety data…