SARAFEM
Clinical safety rating
cautionComprehensive clinical and safety monograph for SARAFEM (SARAFEM).
SARAFEM (fluoxetine) is a selective serotonin reuptake inhibitor (SSRI). It potentiates serotonergic activity in the CNS by inhibiting the reuptake of serotonin at the presynaptic neuronal membrane, enhancing serotonin effects in the synaptic cleft.
| Metabolism | Fluoxetine is extensively metabolized in the liver via the cytochrome P450 enzyme system, primarily CYP2D6, to its active metabolite norfluoxetine. |
| Excretion | Primarily renal excretion of fluoxetine (10%) and its active metabolite norfluoxetine (7.5%) as unchanged drug; the remainder is excreted as conjugates and other metabolites. Approximately 2.5% is excreted in feces. |
| Half-life | Fluoxetine: 4-6 days after single dose, 4-16 days after chronic dosing; norfluoxetine: 4-16 days after single dose, up to 16-20 days after chronic dosing. The long half-life minimizes withdrawal symptoms and allows for once-weekly dosing. |
| Protein binding | Approximately 94.5% bound to plasma proteins, including albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Fluoxetine: 12-43 L/kg; norfluoxetine: 8-43 L/kg. Large Vd indicates extensive tissue distribution, with brain concentrations higher than plasma. |
| Bioavailability | Oral: 72% (range 50-100%), with food not significantly affecting absorption. |
| Onset of Action | Oral: Clinical effects (e.g., mood improvement) may be seen within 1-2 weeks, but full therapeutic effect may require 4-6 weeks or longer due to need to achieve steady-state concentrations. |
| Duration of Action | Due to long half-lives, therapeutic effects persist for weeks after discontinuation; drug levels remain above threshold for 5-6 weeks after stopping chronic therapy. |
| Molecular Weight | 309.33 |
10-20 mg orally once daily initially, may increase to 40 mg/day after 3 weeks if needed; maximum 80 mg/day
| Dosage form | CAPSULE |
| Renal impairment | No adjustment for GFR 20-50 mL/min; avoid use if GFR <20 mL/min |
| Liver impairment | Child-Pugh A: 10 mg/day; Child-Pugh B: 10 mg/day with caution; Child-Pugh C: not recommended |
| Pediatric use | 8-18 years: 10 mg orally once daily initially, may increase to 20 mg/day after 2 weeks |
| Geriatric use | Initial 10 mg orally once daily; increase slowly with minimum effective dose; CYP2D6 interaction concerns |
| 1st trimester | Limited data; potential risk of major malformations, especially cardiac defects, with first trimester exposure. Use only if clearly needed. |
| 2nd trimester | Monitor for gestational hypertension and low birth weight; risk of persistent pulmonary hypertension in the newborn may exist. |
| 3rd trimester | Risk of neonatal adaptation syndrome (respiratory distress, feeding difficulties, irritability) and persistent pulmonary hypertension. Consider tapering near delivery. |
Clinical note
Comprehensive clinical and safety monograph for SARAFEM (SARAFEM).
| Placental transfer | Fluoxetine crosses the placenta extensively. The cord-to-maternal plasma concentration ratio is approximately 0.6–0.9 for fluoxetine and 0.7–0.9 for norfluoxetine, indicating substantial fetal exposure. |
| Breastfeeding | Fluoxetine and its active metabolite norfluoxetine are excreted into breast milk in low to moderate amounts. Infant serum levels can be detectable, especially with maternal doses >20 mg/day. Monitor infant for irritability, poor feeding, and weight gain. The American Academy of Pediatrics considers fluoxetine compatible with breastfeeding but caution is advised, particularly in preterm or compromised infants. |
| Lactation Rating | L2 (Safer) for doses up to 20 mg/day; L3 (Moderately Safe) for higher doses. |
| Teratogenic Risk | First trimester: Associated with increased risk of cardiac malformations (e.g., ventricular septal defects) and persistent pulmonary hypertension of the newborn. Second/third trimester: Risk of preterm birth, low birth weight, and neonatal adaptation syndrome (jitteriness, hypertonia, poor feeding). |
| Fetal Monitoring | Monitor maternal mood, suicidal ideation; fetal ultrasonography for cardiac abnormalities; neonatal surveillance for adaptation syndrome and pulmonary hypertension. |
| Fertility Effects | In animal studies, no impairment of fertility at clinically relevant doses. Human data limited; use may affect menstrual cycle via prolactin elevation. |
■ 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.
| Serious Effects |
Hypersensitivity to fluoxetine or any excipientsConcomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOIConcomitant use with pimozideConcomitant use with thioridazine
| Precautions | Clinical worsening and suicide risk, Serotonin syndrome, Allergic reactions and rash, Abnormal bleeding, Activation of mania/hypomania, Seizures, Angle-closure glaucoma, Hyponatremia, QT prolongation |
| Food/Dietary | No specific food restrictions. Avoid concurrent use of St. John's wort, tryptophan, or 5-HTP due to risk of serotonin syndrome. Grapefruit may increase fluoxetine levels; limit intake. |
| Clinical Pearls | SARAFEM (fluoxetine 10 mg) is indicated for premenstrual dysphoric disorder (PMDD). Dosing is typically 20 mg/day continuous or 20 mg/day intermittent (starting 14 days before menses). Onset of benefit may take 1-2 cycles. Monitor for serotonin syndrome, especially if combined with other serotonergic drugs. Discontinue gradually to avoid withdrawal symptoms. Suicidal thinking risk warning applies, particularly in young adults. |
| Patient Advice | Take SARAFEM exactly as prescribed, with or without food. · It may take several weeks to feel the full benefit; do not stop suddenly. · Report any worsening depression, suicidal thoughts, or unusual behavior changes immediately. · Avoid alcohol while taking this medication. · Inform your doctor of all other medications, especially MAOIs, triptans, or other antidepressants. · May cause drowsiness or dizziness; use caution when driving or operating machinery. |
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