PROZAC WEEKLY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROZAC WEEKLY (PROZAC WEEKLY).

How it works

Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity by blocking reuptake of serotonin at the presynaptic neuronal membrane.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROZAC WEEKLY (PROZAC WEEKLY).

Breastfeeding	Fluoxetine and norfluoxetine are excreted in breast milk. Infant serum concentrations are typically low (<10% maternal weight-adjusted dose). M/P ratio for fluoxetine ~0.8; norfluoxetine ~0.2. Cases of adverse effects (fussiness, poor feeding) are rare. Benefits may outweigh risks in moderate-severe depression.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with MAOIs","Concomitant use with pimozide or thioridazine","Known hypersensitivity to fluoxetine"]

Clinical Precautions

Precautions

["Clinical worsening and suicide risk","Serotonin syndrome","Mania/hypomania","Seizures","Altered platelet function","Angle-closure glaucoma","Hyponatremia","QT prolongation","Sexual dysfunction"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

PROZAC WEEKLY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PROZAC WEEKLY (PROZAC WEEKLY).

How it works

Selective serotonin reuptake inhibitor (SSRI); potentiates serotonergic activity by blocking reuptake of serotonin at the presynaptic neuronal membrane.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PROZAC WEEKLY (PROZAC WEEKLY).

Breastfeeding	Fluoxetine and norfluoxetine are excreted in breast milk. Infant serum concentrations are typically low (<10% maternal weight-adjusted dose). M/P ratio for fluoxetine ~0.8; norfluoxetine ~0.2. Cases of adverse effects (fussiness, poor feeding) are rare. Benefits may outweigh risks in moderate-severe depression.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with MAOIs","Concomitant use with pimozide or thioridazine","Known hypersensitivity to fluoxetine"]

Clinical Precautions

Precautions

["Clinical worsening and suicide risk","Serotonin syndrome","Mania/hypomania","Seizures","Altered platelet function","Angle-closure glaucoma","Hyponatremia","QT prolongation","Sexual dysfunction"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…