FLUOXETINE HYDROCHLORIDE
Clinical safety rating: caution
MAOIs can cause serotonin syndrome and other SSRIs may have additive effects May increase risk of bleeding especially with NSAIDs or warfarin.
Selective serotonin reuptake inhibitor (SSRI); increases serotonergic activity by blocking the reuptake of serotonin at the presynaptic neuron, leading to increased serotonin levels in the synaptic cleft.
| Metabolism | Primarily metabolized by CYP2D6, also CYP2C9 and CYP3A4; active metabolite norfluoxetine (N-demethylation). |
| Excretion | Primarily renal (80%), with approximately 10% eliminated as unchanged fluoxetine and 90% as metabolites (mainly norfluoxetine). Fecal excretion accounts for about 15% of the dose. |
| Half-life | Fluoxetine: 4-6 days; Norfluoxetine: 9.3 days (range 4-16 days). Steady-state is achieved after 4-5 weeks. Clinical implications: requires long washout period (5 weeks) before initiating MAOIs. |
| Protein binding | 94.5% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 12-43 L/kg (mean 25 L/kg). Indicates extensive tissue distribution (e.g., brain, lungs). |
| Bioavailability | Oral: 72-95% (mean 80%). |
| Onset of Action | Oral: 1-2 weeks for initial clinical improvement; full therapeutic effect may require 4-8 weeks. |
| Duration of Action | Extended due to long half-life; therapeutic effect persists for weeks after discontinuation. Once-daily dosing maintains steady-state. |
20 mg orally once daily; may increase after several weeks to max 80 mg/day
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: no adjustment; GFR <10 mL/min: use lower dose (e.g., 20 mg every other day) due to prolonged half-life. Dialysis: supplemental dose not needed. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% (e.g., 20 mg every other day) or use 10 mg daily; Child-Pugh C: not recommended or use extreme caution with 10 mg every other day. |
| Pediatric use | Children 8-18 years: 10 mg orally once daily initially; after 1 week increase to 20 mg daily; max 60 mg/day. Weight-based: 0.5-1 mg/kg/day typical. |
| Geriatric use | Start at 10 mg orally once daily; increase slowly to 20 mg daily; max typically 40 mg/day due to increased half-life and sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause serotonin syndrome and other SSRIs may have additive effects May increase risk of bleeding especially with NSAIDs or warfarin.
| FDA category | Animal |
| Breastfeeding | Fluoxetine and its active metabolite norfluoxetine are excreted into breast milk. M/P ratio for fluoxetine is approximately 0.6-1.0 (range 0.2-2.1), and for norfluoxetine ~0.3-0.9. Infant serum levels are typically low (subtherapeutic), but accumulation may occur due to long half-life. Reported adverse events include colic, irritability, and poor feeding. Caution is advised, especially with high maternal doses and in preterm infants. |
■ 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 | OCD |
| Serious Effects |
["Concomitant use with MAOIs or within 14 days of MAOI discontinuation","Concomitant use with pimozide or thioridazine","QTc prolongation or congenital long QT syndrome","Hypersensitivity to fluoxetine or any formulation component"]
| Precautions | ["Suicidality risk","Serotonin syndrome","QT prolongation","Activation of mania/hypomania","Seizures","Abnormal bleeding","Angle-closure glaucoma","Hyponatremia","Sexual dysfunction","Discontinuation syndrome"] |
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| Teratogenic Risk |
| First trimester: Epidemiological studies have reported an increased risk of congenital cardiac malformations (e.g., ventricular septal defect) with exposure, particularly at higher doses (absolute risk ~2-3% vs 1% baseline). Third trimester: Exposure increases risk of persistent pulmonary hypertension of the newborn (PPHN, about 1.5-2 per 1000 live births). Late third trimester: Neonatal adaptation syndrome (including respiratory distress, feeding difficulties, jitteriness) in up to 30% of exposed neonates. |
| Fetal Monitoring | Maternal: Monitor for depressive symptoms, suicidal ideation, and side effects (e.g., nausea, anxiety, sexual dysfunction). Fetal: Consider fetal echocardiography at 18-22 weeks if first-trimester exposure. Neonatal: Observe for signs of neonatal adaptation syndrome (e.g., respiratory distress, poor feeding, irritability) for at least 48 hours after delivery. |
| Fertility Effects | Fluoxetine may cause sexual dysfunction (e.g., decreased libido, delayed orgasm) in both men and women, potentially impacting fertility. In women, SSRIs can alter menstrual cycle and ovulation, though effect on conception is not consistently observed. In men, reversible sperm abnormalities (e.g., decreased motility) have been reported. Overall, effect on fertility is considered minimal but may be clinically relevant in some individuals. |