PROZAC WEEKLY
Clinical safety rating
cautionComprehensive clinical and safety monograph for PROZAC WEEKLY (PROZAC WEEKLY).
Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity by blocking reuptake of serotonin at the presynaptic neuronal membrane.
| Metabolism | Hepatic via CYP2D6, CYP2C9, and CYP3A4; active metabolite norfluoxetine. |
| Excretion | Renal excretion of metabolites (primarily fluoxetine glucuronide and norfluoxetine glucuronide) accounts for approximately 80% of elimination; fecal excretion accounts for approximately 15%. |
| Half-life | Fluoxetine: 4-6 days after single dose, 4-6 days (extended to 7-9 days with chronic dosing due to autoinhibition of CYP2D6); norfluoxetine: 9-31 days. Steady state achieved after 2-4 weeks. |
| Protein binding | Approximately 94.5% bound to plasma proteins, including albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 12-43 L/kg (average ~25 L/kg). Large Vd indicates extensive tissue distribution, including brain and fat; contributes to prolonged elimination. |
| Bioavailability | Oral: ~90% (not significantly affected by food). Weekly formulation: same bioavailability as daily dosing. |
| Onset of Action | Oral: Clinical effects (e.g., mood improvement) typically begin within 1-2 weeks, but full therapeutic benefit may require 4-8 weeks or longer. No difference in onset for weekly vs daily dosing. |
| Duration of Action | Therapeutic effects persist for weeks after discontinuation due to long half-lives of fluoxetine and norfluoxetine; washout period of at least 5 weeks recommended before starting MAOIs. |
| Molecular Weight | 345.79 |
90 mg orally once weekly
| Dosage form | CAPSULE, DELAYED REL PELLETS |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min; insufficient data for GFR <15 mL/min, use with caution. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: initiate at 20 mg/day (immediate-release) or use alternative; Class C: contraindicated or use with extreme caution. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate with 20 mg/day (immediate-release) and increase cautiously; monitor for hyponatremia and SIADH; PROZAC WEEKLY not recommended due to limited data. |
| 1st trimester | Risk of cardiovascular malformations and persistent pulmonary hypertension in neonates. Limited human data suggest increased risk of miscarriage and preterm birth. |
| 2nd trimester | Increased risk of preeclampsia and preterm birth. Monitor for serotonin syndrome and maternal bleeding. |
| 3rd trimester | Risk of neonatal adaptation syndrome (e.g., respiratory distress, feeding difficulties, irritability). Avoid late third trimester use if possible. |
Clinical note
Comprehensive clinical and safety monograph for PROZAC WEEKLY (PROZAC WEEKLY).
| Placental transfer | Passes placental barrier; ratio of umbilical cord to maternal plasma concentration approximately 0.8–1.0. |
| Breastfeeding | Fluoxetine and its metabolite norfluoxetine are excreted into breast milk with an infant relative dose of 2.4–11.3%. Cases of irritability, poor feeding, and sleep disturbances in breastfed infants have been reported. Use with caution, especially in preterm infants or those with impaired metabolism. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Crosses placenta; risk of major congenital malformations based on some studies (e.g., cardiovascular defects approx. 1.8% vs 1% baseline). Third trimester: Risk of persistent pulmonary hypertension of the newborn (PPHN) approx. 0.3% vs 0.1% baseline. Late trimester: Neonatal adaptation syndrome (irritability, feeding difficulties, respiratory distress) in ~30% exposed neonates. |
| Fetal Monitoring | Maternal: Assess depression severity, suicidal ideation; monitor for serotonin syndrome, mania. Fetal/Neonatal: Consider third trimester ultrasound for growth; postnatal monitor for neonatal adaptation syndrome (irritability, feeding problems, respiratory distress), PPHN. |
| Fertility Effects | May cause hyperprolactinemia (rare) leading to galactorrhea, menstrual disturbances, and reversible infertility. Data on direct ovulatory dysfunction limited. No proven permanent impairment. |
■ 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 |
Concurrent use of MAOIs or within 14 days of MAOI discontinuationConcurrent use of pimozide or thioridazineFluoxetine hypersensitivity
| Precautions | Clinical worsening and suicide risk, Serotonin syndrome, Mania/hypomania, Seizures, Altered platelet function, Angle-closure glaucoma, Hyponatremia, QT prolongation, Sexual dysfunction |
| Food/Dietary | Grapefruit and grapefruit juice may increase fluoxetine levels; avoid large amounts. No specific dietary restrictions, but take with food if GI upset occurs. |
| Clinical Pearls | Fluoxetine has a long half-life (4-6 days; active metabolite norfluoxetine 4-16 days) allowing weekly dosing, but requires daily loading for 13 weeks before switching to weekly. Monitor for serotonin syndrome if co-prescribed with other serotonergic drugs. Abrupt discontinuation may cause withdrawal symptoms despite long half-life. |
| Patient Advice | Take once weekly on the same day, typically 90 mg capsule. Do not crush or chew. · May take 4-8 weeks for full therapeutic effect. · Common side effects include nausea, insomnia, drowsiness, sweating, and sexual dysfunction. · Avoid alcohol as it may worsen side effects. · Contact doctor if rash, suicidal thoughts, or serotonin syndrome symptoms occur. · Do not stop abruptly; withdrawal effects possible. |
Loading safety data…