SARAFEM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SARAFEM (SARAFEM).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SARAFEM (SARAFEM).

Breastfeeding	Fluoxetine is excreted into breast milk; M/P ratio ~0.3-0.6. Relative infant dose estimated at 2-4% of maternal dose. Monitor infant for drowsiness, poor feeding, and irritability.
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

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 discontinuing an MAOI","Concomitant use with pimozide or thioridazine","Known hypersensitivity to fluoxetine or any component of the formulation"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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SARAFEM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SARAFEM (SARAFEM).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SARAFEM (SARAFEM).

Breastfeeding	Fluoxetine is excreted into breast milk; M/P ratio ~0.3-0.6. Relative infant dose estimated at 2-4% of maternal dose. Monitor infant for drowsiness, poor feeding, and irritability.
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

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 discontinuing an MAOI","Concomitant use with pimozide or thioridazine","Known hypersensitivity to fluoxetine or any component of the formulation"]