Fluoxetine
Prozac | Sarafem
Overview
Selective serotonin reuptake inhibitor (SSRI) and the first drug in its class, widely used for depression, OCD, and eating disorders.
Indications
- Major depressive disorder
- Obsessive-compulsive disorder
- Bulimia nervosa
- Panic disorder
- Premenstrual dysphoric disorder
Contraindications
- Use of MAOIs within 14 days (or 5 weeks after stopping fluoxetine)
- Concurrent pimozide or thioridazine
Classification
Mechanism of Action
Selectively inhibits serotonin reuptake at the presynaptic neuron, increasing serotonin availability in the synaptic cleft.
Pharmacodynamics
SSRI with the longest half-life in its class. Therapeutic effects typically appear after 2-4 weeks of treatment.
Pharmacokinetics
- Absorption
- Well absorbed orally. Not significantly affected by food.
- Distribution
- Highly lipophilic. Extensive tissue distribution.
- Metabolism
- Hepatic via CYP2D6 to active metabolite norfluoxetine.
- Excretion
- Renal (80%), fecal (15%).
- Half-life
- 1-3 days (fluoxetine); 4-16 days (norfluoxetine)
- Bioavailability
- 72%
- Protein Binding
- 94.5%
Dosage
Typical dosage: 20-80mg once daily
Available Forms
- Capsule
- Tablet
- Oral solution
- Delayed-release capsule (weekly)
Side Effects
Common
- Nausea
- Headache
- Insomnia
- Anxiety
- Sexual dysfunction
- Decreased appetite
Serious
- Serotonin syndrome
- Suicidal ideation (age <25)
- QT prolongation
- Hyponatremia
Rare
- Seizures
- Angle-closure glaucoma
- Serotonin discontinuation syndrome (less common due to long half-life)
Drug Interactions
Risk of fatal serotonin syndrome. Wait 14 days after MAOI before starting, and 5 weeks after stopping fluoxetine before starting MAOI (due to long half-life).
Fluoxetine strongly inhibits CYP2D6, blocking conversion of tamoxifen to its active metabolite endoxifen, reducing breast cancer treatment efficacy.
Warnings
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. Monitor for clinical worsening and suicidality.
Pregnancy
Category C
Toxicity
LD50 452 mg/kg (oral, rat)
Overdose
Symptoms: nausea, vomiting, seizures, cardiac arrhythmias, coma. Treatment: activated charcoal, supportive care, cardiac monitoring.
References
Looking for patient-friendly information? Visit RemedyDoor for easy-to-read guides about this medication.