FLUOCET

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FLUOCET (FLUOCET).

How it works

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by blocking the reuptake of serotonin into presynaptic neurons.

What the body does with it

Metabolism	Primarily hepatic, via CYP2D6 and CYP2C9 isoenzymes; active metabolite norfluoxetine.
Excretion	Renal: 80% as fluoxetine and its metabolites (60% as glucuronide conjugates, 20% as parent and norfluoxetine). Fecal: 15% (biliary).
Half-life	Fluoxetine: 4-6 days (single dose), 4-6 days (chronic); Norfluoxetine: 16 days. Clinical context: Steady state achieved after 4-5 weeks; extended half-life reduces withdrawal risk but prolongs washout.
Protein binding	94.5% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd: 12-42 L/kg (mean 27 L/kg). Clinical meaning: Extensive tissue distribution (CNS, lungs, liver).
Bioavailability	Oral: 60-80% (mean 72% due to first-pass metabolism). Food does not affect bioavailability significantly.
Onset of Action	Oral: 2-4 weeks for antidepressant effect; 4-8 weeks for full therapeutic response. IV: Not applicable.
Duration of Action	Oral: Effects persist for 2-3 weeks after discontinuation due to long half-life. Clinical notes: 5-week washout required before MAOI initiation.

Classification & Brands

Dosing & administration

20 mg orally once daily in the morning.

Dosage form	CREAM
Renal impairment	No dose adjustment required for GFR 15-50 mL/min; not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh A: 20 mg daily; Child-Pugh B: 10 mg daily; Child-Pugh C: not recommended.
Pediatric use	Children 8-18 years: 10 mg orally once daily; may increase to 20 mg after 2 weeks if needed.
Geriatric use	Initial dose 10 mg orally once daily; increase to 20 mg with caution.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for FLUOCET (FLUOCET).

Breastfeeding

Fluoxetine and its active metabolite norfluoxetine are excreted into breast milk, with an estimated infant dose of 2-12% of maternal weight-adjusted dose. M/P ratio: fluoxetine ~0.3-0.8, norfluoxetine ~0.2-0.4. Breastfeeding is generally considered compatible, but monitor infant for excessive sedation, poor feeding, or irritability.

Teratogenic Risk

Fluoxetine use in the first trimester is associated with a small increased risk of congenital cardiac malformations (odds ratio ~1.2). Exposure in the third trimester may cause persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome (irritability, feeding difficulties, respiratory distress). Late pregnancy exposure also increases risk of preterm birth and lower birth weight.

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 or within 14 days of MAOI discontinuation","Concomitant use with pimozide or thioridazine","Hypersensitivity to fluoxetine or any component"]

Clinical Precautions

Precautions

["Serotonin syndrome","Suicidality in pediatric patients","Bleeding risk (especially with NSAIDs/aspirin)","Activation of mania/hypomania","QT prolongation (caution in electrolyte disturbances, bradycardia)","Seizures","Angle-closure glaucoma","Hyponatremia","Sexual dysfunction","Discontinuation syndrome"]

Clinical Tips & Counseling

Drug interactions

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FLUOCET

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FLUOCET (FLUOCET).

How it works

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that potentiates serotonergic activity in the CNS by blocking the reuptake of serotonin into presynaptic neurons.

What the body does with it

Metabolism	Primarily hepatic, via CYP2D6 and CYP2C9 isoenzymes; active metabolite norfluoxetine.
Excretion	Renal: 80% as fluoxetine and its metabolites (60% as glucuronide conjugates, 20% as parent and norfluoxetine). Fecal: 15% (biliary).
Half-life	Fluoxetine: 4-6 days (single dose), 4-6 days (chronic); Norfluoxetine: 16 days. Clinical context: Steady state achieved after 4-5 weeks; extended half-life reduces withdrawal risk but prolongs washout.
Protein binding	94.5% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd: 12-42 L/kg (mean 27 L/kg). Clinical meaning: Extensive tissue distribution (CNS, lungs, liver).
Bioavailability	Oral: 60-80% (mean 72% due to first-pass metabolism). Food does not affect bioavailability significantly.
Onset of Action	Oral: 2-4 weeks for antidepressant effect; 4-8 weeks for full therapeutic response. IV: Not applicable.
Duration of Action	Oral: Effects persist for 2-3 weeks after discontinuation due to long half-life. Clinical notes: 5-week washout required before MAOI initiation.

Classification & Brands

Dosing & administration

20 mg orally once daily in the morning.

Dosage form	CREAM
Renal impairment	No dose adjustment required for GFR 15-50 mL/min; not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh A: 20 mg daily; Child-Pugh B: 10 mg daily; Child-Pugh C: not recommended.
Pediatric use	Children 8-18 years: 10 mg orally once daily; may increase to 20 mg after 2 weeks if needed.
Geriatric use	Initial dose 10 mg orally once daily; increase to 20 mg with caution.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for FLUOCET (FLUOCET).

Breastfeeding

Teratogenic Risk

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 or within 14 days of MAOI discontinuation","Concomitant use with pimozide or thioridazine","Hypersensitivity to fluoxetine or any component"]