# Prozac ### (fluoxetine) **[Prozac](https://wiki.joshnp.com/link/147)** (fluoxetine); not controlled
[**Full Prescribing Information**](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=c88f33ed-6dfb-4c5e-bc01-d8e36dd97299&type=display)[**DailyMed Drug Information**](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c88f33ed-6dfb-4c5e-bc01-d8e36dd97299)
--- ### **Summary** Prozac is a selective serotonin reuptake inhibitor approved for major depressive disorder from 8 years of age and for obsessive-compulsive disorder from 7 years. Response is judged over weeks of continuous dosing. Its half-life is the longest in the class, so it is effectively self-tapering and forgiving of a missed dose. Not controlled; brand and generic. --- ### **Forms & Strengths** - **Capsules, immediate release:** 10 mg, 20 mg, 40 mg - **Tablets:** 10 mg, 20 mg, 60 mg - **Oral solution:** 20 mg/5 mL (4 mg/mL) - **Capsule, delayed release, once weekly:** 90 mg. A separate label; NEVER studied in children - **Olanzapine and fluoxetine capsules:** fluoxetine 25 mg or 50 mg with olanzapine 3, 6 or 12 mg --- ### **Dosing** - **Age:** - MDD: 8 y/o and older - OCD: 7 y/o and older - Bipolar I depression, with olanzapine: 10 y/o and older - **Onset:** 4 weeks or longer in MDD; 5 weeks or longer in OCD - **Duration:** continuous with once-daily dosing - **Initial Dose:** - Pediatric MDD: 10 or 20 mg/day; 10 mg/day if lower weight - Pediatric OCD: 10 mg/day at any weight - Adults: 20 mg/day - **Titration:** - Pediatric MDD: to 20 mg/day after 1 week; OCD: to 20 mg/day after 2 weeks - Further increases only after several more weeks, never weekly - **Max Dose:** - Ceiling at any age or indication: 80 mg/day - Pediatric OCD: 60 mg/day, or 30 mg/day if lower weight - Pediatric MDD: no separate maximum; trials used 10 to 20 mg/day - **Considerations:** Give in the morning; a dose above 20 mg/day may be split between morning and noon. Use a lower or less frequent dose in cirrhosis. --- ### **Pharmacology** - **Mechanism:** Blocks presynaptic serotonin reuptake at SERT, without the tricyclics' anticholinergic and sedative burden - **Delivery / Release:** immediate release; food does not affect bioavailability - **Metabolism:** hepatic via CYP2D6 to active norfluoxetine. Half-life 4 to 6 days on chronic dosing, norfluoxetine 4 to 16 days, steady state at 4 to 5 weeks - **Class Positioning:** a POTENT CYP2D6 inhibitor persisting up to 5 weeks after the last dose, unlike [Zoloft](https://wiki.joshnp.com/link/148). The only SSRI with a pediatric MDD indication --- ### **Indications** - **Major Depressive Disorder** (ICD-10: F32.x, F33.x): 8 y/o and older - **Obsessive-Compulsive Disorder** (ICD-10: F42.x): 7 y/o and older - **Bulimia Nervosa** (ICD-10: F50.2): adults only, at 60 mg/day - **Panic Disorder** (ICD-10: F41.0): adults only - **Bipolar I depression, with olanzapine only** (ICD-10: F31.x): 10 y/o and older - **Treatment-resistant depression, with olanzapine only**: adults --- ### **Off-Label Uses** - **Pediatric anxiety disorders** (ICD-10: F41.1, F40.10, F93.0): supported; AHRQ graded SSRIs moderate to high, with CBT outperforming fluoxetine (AHRQ 2017). On-label alternative: [Cymbalta](https://wiki.joshnp.com/link/100) from 7 y/o - **MDD in CHILDREN rather than adolescents** (ICD-10: F32.x): graded low in adolescents, INSUFFICIENT in children (AACAP 2023) - **Bulimia nervosa in adolescents** (ICD-10: F50.2): insufficient at any dose --- ### **Contraindications & Warnings** - **Boxed Warning:** SUICIDAL THOUGHTS AND BEHAVIORS in children, adolescents and young adults. - Monitor closely for worsening and emergent suicidality in the initial few months and at every dose change, up or down. - Observation must include DAILY observation at home. Dispense the smallest quantity consistent with good management. - **Contraindicated:** - An MAOI concurrently, within 5 WEEKS of stopping Prozac, or Prozac within 14 days of an MAOI. That 5-week exit washout is longer than the rest of the class, set by norfluoxetine's half-life. - Linezolid or intravenous methylene blue. - Pimozide and thioridazine; fluoxetine raises both via CYP2D6 and all three prolong QT. - **Use with caution:** - Seizure history; long QT, hypokalemia, hypomagnesemia, recent myocardial infarction, heart failure, bradyarrhythmias. - Narrow angles without a patent iridectomy; diabetes; cirrhosis, needing a lower dose. - Underweight patients; NSAIDs, aspirin, anticoagulants, diuretics; prior rash on fluoxetine. - **Screen before starting:** - Personal and family history of bipolar disorder, mania or hypomania; baseline height, weight and sexual function. - QT risk factors, and a medication list for CYP2D6 substrates, MAOIs and anticoagulants. --- ### **Drug Interactions** - **MAOIs** (phenelzine, selegiline, linezolid, methylene blue): contraindicated. 14 days before starting Prozac, 5 WEEKS after stopping it - **CYP2D6 substrates including atomoxetine** ([Strattera](https://wiki.joshnp.com/link/4), TCAs, antipsychotics): start low, and treat anyone dosed within the previous 5 weeks as still on fluoxetine. - For atomoxetine, lengthen the titration interval to 4 weeks rather than lowering the target dose. - This pair, and [Qelbree](https://wiki.joshnp.com/link/36), stack two pediatric suicidality boxed warnings. - **Bupropion** ([Wellbutrin XL](https://wiki.joshnp.com/link/98)): doubles 2D6 inhibition and stacks seizure cautions - **Other serotonergic drugs** (SSRIs, SNRIs, triptans, tramadol, lithium, AMPHETAMINES): serotonin syndrome. Stop all for agitation, hyperthermia, rigidity or myoclonus - **Tricyclics, phenytoin, carbamazepine:** levels rise for weeks; check when fluoxetine starts and stops - **NSAIDs, aspirin, warfarin:** bleeding; check the INR at both ends - **QT-prolonging drugs** (ziprasidone, erythromycin, amiodarone, methadone): avoid, or obtain an ECG before each increase --- ### **Administration** - Give once daily in the morning; split a dose above 20 mg for daytime nausea rather than reducing it. - With or without food. Swallow capsules and tablets whole; the oral solution is the only form delivering below 10 mg. - Missed dose: resume at the next dose; do not double up. - Never use the 90 mg once-weekly capsule in a pediatric patient or in place of daily dosing. - Switching to an MAOI: allow 5 weeks off fluoxetine. From an MAOI: allow 14 days. --- ### **Side Effects** - **Common:** nausea, insomnia, nervousness, somnolence, anxiety, diarrhea, anorexia, dry mouth, tremor, asthenia. - Pediatric trials add thirst, hyperkinesia, agitation, epistaxis, urinary frequency and menorrhagia. - **Serious:** - Suicidal thoughts and behavior: the boxed warning. Change the regimen, including stopping, if suicidality emerges. - Serotonin syndrome: stop every serotonergic agent immediately and treat supportively. - Mania or hypomania, in 2.6% of pediatric patients. Stop and reassess for bipolar disorder. - Rash and systemic hypersensitivity. Discontinue on any unexplained rash. - Hyponatremia and SIADH; QT prolongation and torsades; seizures. - Growth lag: 1.1 cm and 1.1 kg below placebo at 19 weeks. - Bleeding; angle-closure glaucoma; sexual dysfunction. --- ### **Monitoring & Labs** - **Suicidality:** every visit for 3 months, at every dose change in either direction, then every 3 months. Instruct the family in DAILY home observation for the first month - **Activation and mania:** screen for bipolar history before the first dose, then ask about reduced sleep need, pressured speech and elevated mood every 3 months - **Growth:** plot height and weight at baseline, every 3 months for the first year, then every 6 months - **Hyponatremia:** check sodium for new headache, confusion or unsteadiness, or when a diuretic is started - **Bleeding:** ask about bruising and nosebleeds every 3 months; check the INR on warfarin - **Response:** do not judge efficacy before 4 weeks in MDD or 5 weeks in OCD; reassess every 6 months, with sexual function --- ### **Discontinuation & Taper** - Effectively self-tapering: both fluoxetine and norfluoxetine fall gradually at the end of therapy, minimizing discontinuation symptoms. - The contrast that drives drug choice: [Zoloft](https://wiki.joshnp.com/link/148) has a 26-hour half-life and must be reduced gradually. Where adherence is unreliable, fluoxetine is safer. - A gradual reduction is still preferred; reactions include dysphoric mood, irritability, dizziness, electric shock sensations and insomnia. If they follow a decrease, resume the previous dose. - Drug holidays are not appropriate; steady state takes 4 to 5 weeks, so a break resets the clock. - Interactions outlast the drug: for 5 weeks an MAOI and thioridazine stay contraindicated. --- ### **Pregnancy & Lactation** - **Pregnancy:** decades of data have not established increased risk of major birth defects or miscarriage. - Later exposure may raise the risk of persistent pulmonary hypertension of the newborn; third-trimester exposure has produced respiratory distress, feeding difficulty, hypotonia and irritability. - Weigh rather than abstain: women who stopped antidepressants in pregnancy relapsed more often. - **Lactation:** present in human milk; agitation, irritability, poor feeding and poor weight gain reported. - Milk levels run HIGHER than most other SSRIs, relative infant dose roughly 2.4% to 7%, with no adverse developmental effects to 5 years (LactMed 2026). - [Zoloft](https://wiki.joshnp.com/link/148) is the lower-exposure choice when starting an SSRI while nursing. - **Exposure Registry:** National Pregnancy Registry for Antidepressants, 1-844-405-6185, [womensmentalhealth.org](https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/) --- ### **Counseling Points** - **Counsel the family on:** - Nothing much happening for two weeks. Name the review point aloud: 4 weeks for depression, 5 for OCD. - Taking it in the morning, and splitting a dose above 20 mg if nausea is the problem. - A missed dose being forgiving here, and a dose increase taking weeks to show for the same reason. - Never accepting a 90 mg once-weekly capsule; it has never been studied in children. - Telling every future prescriber about fluoxetine taken within the last 5 weeks. - Daily home observation for the first month for out-of-character behaviour. - **Advise them to call for:** - New or worsening talk of self-harm, or any abrupt mood change after a dose change. - Days without needing sleep, much faster speech, or a jump in energy. - Any rash or hives, particularly with fever or joint swelling. - Shivering, twitching, stiffness, racing heart, sweating and confusion together. - Nosebleeds that will not stop, unexplained bruising, or black stools. - Fainting, irregular heartbeat, or a seizure. --- ### **References** 1. DailyMed. Prozac (fluoxetine) capsule. Dista Products Company. 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c88f33ed-6dfb-4c5e-bc01-d8e36dd97299 2. DailyMed. Fluoxetine delayed release capsule, 90 mg weekly. Dr. Reddy's. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=887fc670-db67-4cfe-967b-46b38375dae5 3. LactMed. Fluoxetine. 2026. https://www.ncbi.nlm.nih.gov/books/NBK501186/ 4. AHRQ. Anxiety in children. CER No. 192, 17-EHC023-EF. 2017. https://www.ncbi.nlm.nih.gov/books/NBK476277/ 5. AACAP. Depressive disorders practice guideline. 2023. PMID 36273673. https://www.jaacap.org/article/S0890-8567(22)01852-4/fulltext 6. FDA. NDC Directory, openFDA, generic name fluoxetine. 2026. https://api.fda.gov/drug/ndc.json?search=generic\_name:%22fluoxetine%22&limit=1000