Fluoxetine Capsules

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for various conditions, including mood disorders, anxiety-related disorders, and certain eating disorders.

Fluoxetine may assist with major depressive disorder, obsessive-compulsive disorder, panic disorder, bulimia nervosa, bipolar I depression, and treatment-resistant depression when used in combination with olanzapine.^[1]

Fluoxetine may selectively inhibit the reuptake of serotonin in presynaptic neurons, increasing its availability in the brain. This action may help improve mood and alleviate depressive symptoms. It may assist with blocking serotonin transport proteins, with mild activity on 5-HT2A and 5-HT2C receptors. Fluoxetine has minimal impact on norepinephrine reuptake.^[1]

Contraindications & Precautions:
Fluoxetine is contraindicated in patients with a known hypersensitivity to the drug or any of its components. Additionally, fluoxetine should not be used concurrently with monoamine oxidase inhibitors (MAOIs) or initiated within two weeks of discontinuing an MAOI, as this may increase the risk of serotonin syndrome.

Fluoxetine has a black box warning for the potential risk of suicidal ideation, with studies suggesting that this risk may be higher in children and young adults.

Caution is advised when prescribing fluoxetine to individuals with a history of seizures, bipolar disorder, glaucoma, or increased risk of QT prolongation, as the medication may trigger seizures, mania, hypomania, or other serious reactions. Additionally, patients may experience unwanted effects such as hyponatremia, cognitive impairment, and sexual dysfunction, necessitating close monitoring and individualized assessment.^[1]

SSRIs, including fluoxetine, have been associated with clinically significant hyponatremia, often resulting from syndrome of inappropriate antidiuretic hormone secretion (SIADH). This electrolyte imbalance may lead to a range of symptoms, from mild cognitive impairment to severe neurological complications like seizures and coma. Studies suggest that the risk of SSRI-induced hyponatremia is higher in elderly patients, those taking diuretics, or those prone to dehydration. Monitoring of serum sodium levels is recommended, especially during the early weeks of fluoxetine therapy for vulnerable patient populations.^[1][2]

Caution is advised when prescribing fluoxetine to elderly patients, particularly those with or at risk for osteoporosis. Studies have suggested a potential association between SSRI use, including fluoxetine, and an increased risk of nonvertebral fractures in older adults. This risk appears to increase with prolonged use. Patients with pre-existing osteoporosis or those at elevated risk may require more frequent monitoring and careful consideration of the risks and benefits of long-term SSRI use.^[3]

NOTE: This list may not include all possible contraindications.

Fluoxetine may interact with various medications, potentially altering their serum concentrations and effects. This is due to its inhibition of the CYP2D6 enzyme, which plays a crucial role in metabolizing various medications like tricyclic antidepressants (TCAs), antipsychotics, and antiarrhythmics.^[1]

Fluoxetine may substantially increase TCA serum levels, which may necessitate dosage adjustments to prevent toxicity.^[1][4] Similarly, interactions with certain antipsychotics like haloperidol and clozapine may result in elevated plasma concentrations, potentially enhancing both therapeutic effects and side effects.^[5]

Cardiovascular medications may also be affected. Fluoxetine’s concurrent use with Class 1A medications and Class III antiarrhythmic drugs may potentially prolong the QT interval, potentially increasing the risk of serious cardiac arrythmias.^[1][6]

Fluoxetine may also interact with benzodiazepines. Increased plasma concentrations of alprazolam and diazepam may occur, potentially leading to enhanced sedation and impaired psychomotor function.^[1]

Anticoagulant therapy, particularly with warfarin, requires special attention when combined with fluoxetine. This combination can potentiate warfarin’s anticoagulant effects, which may increase the risk of bleeding. Regular monitoring of PT/INR is essential in these cases.^[1][7]

Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, when used concurrently with fluoxetine, can increase the risk of upper gastrointestinal bleeding.^[8]

Anticonvulsant medications like phenytoin and carbamazepine may also interact with fluoxetine, potentially leading to altered plasma concentrations. Therapeutic drug monitoring may be necessary when used concurrently.^[9]

Fluoxetine may contribute to the development of serotonin syndrome, especially when combined with other serotonergic agents. These include triptans, other antidepressants, opioids like fentanyl and tramadol, and herbal supplements like St. John’s Wort. If serotonin syndrome is suspected, immediate discontinuation of all serotonergic agents is recommended.^[10][11]

NOTE: This is not a comprehensive list of medications that may interact with fluoxetine. For a complete understanding of potential interactions, please consult a healthcare professional or specialized resource.

Common side effects of antidepressants like fluoxetine may include gastrointestinal disturbances like nausea, vomiting, diarrhea, abdominal pain, and constipation. Fluoxetine may also lead to weight fluctuations.^[12]

Less common effects may include rare extrapyramidal symptoms, such as dystonia, and torticollis.^[13] Fluoxetine may also trigger manic episodes, particularly in individuals with undiagnosed bipolar disorder.^[1]

Fluoxetine may potentially cause serious side effects such as serotonin syndrome, a potentially life-threatening condition characterized by various symptoms, including agitation, hallucinations, rapid heart rate, and fluctuating blood pressure.^[11]

The risk of suicidal ideation and behavior, particularly in adolescents and young adults, may demand close observation, especially when initiated.^[1]

Fluoxetine may also potentially increase the risk of glaucoma in certain susceptible populations, although rare.^[14]

Abrupt discontinuation of fluoxetine may lead to withdrawal symptoms such as mood changes, irritability, agitation, dizziness, numbness or tingling in the hands or feet, anxiety, sweating, confusion, headache, tiredness, and difficulty falling asleep or staying asleep.^[15]

Fluoxetine may increase the risk of bleeding and should be used cautiously in certain populations. This potential risk is attributed to fluoxetine’s effect on serotonin reuptake in platelets, which may impair normal clotting function. Patients with a history of bleeding disorders, and those taking anticoagulants or antiplatelet agents concomitantly may be at a higher risk.^[16]

Adults may report side effects such as insomnia, nausea, diarrhea, anorexia, dry mouth, headache, drowsiness, anxiety, nervousness, yawning, bruising, and potential occurrences of seizures and bleeding. Other notable effects may include hyperhidrosis, potential for mania, and activation of suicidal ideation and behavior, particularly in teenagers. Weight changes, decreased orgasm (anorgasmia and ejaculation latency), muscle weakness, tremors, and pharyngitis may also be associated with fluoxetine.^[1]

Additional side effects may include nervousness, anxiety, sleep disturbances, heartburn, weakness, uncontrollable shaking, unusual dreams, and nasal congestion. Sexual issues may arise for both genders, with men potentially experiencing decreased sex drive, erectile difficulties, or delayed/absent ejaculation, while women may potentially face reduced sex drive or delayed orgasms. Cognitive effects such as confusion, difficulty concentrating, and memory problems may also occur.^[1]

NOTE: This list may not include all possible adverse reactions or side effects.

Fluoxetine use during pregnancy requires careful consideration due to potential risks to the fetus. While some studies indicate no significant increase in miscarriage or birth defects, there is a possibility of complications such as preterm delivery and poor neonatal adaptation (PNA), particularly when taken in the third trimester.
If treatment with fluoxetine is necessary during pregnancy, a thorough discussion of the potential risks and benefits should be conducted with a healthcare provider.^[18][19]

Fluoxetine is present in breast milk. In one study, most infants exposed to it showed no significant adverse effects. However, some infants may experience irritability, poor feeding, or sleep disturbances. Monitoring breast-fed infants for adverse effects is advised if fluoxetine use is necessary.
If treatment with fluoxetine is necessary during breastfeeding, a thorough discussion of the potential risks and benefits should be conducted with a healthcare provider.^[18][19]

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

1. Sohel AJ, Shutter MC, Patel P, et al. Fluoxetine. [Updated 2024 Feb 28]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459223/
2. Shakibaei F, Gholamrezaei A, Alikhani M, Talaeizadeh K. Serum sodium changes in fluoxetine users at different age groups. Iran J Psychiatry. 2010 Summer;5(3):113-6.
3. Ziere G, Dieleman JP, van der Cammen TJ, Hofman A, Pols HA, Stricker BH. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008 Aug;28(4):411-7. doi: 10.1097/JCP.0b013e31817e0ecb.
4. Deodhar M, Rihani SBA, Darakjian L, Turgeon J, Michaud V. Assessing the Mechanism of Fluoxetine-Mediated CYP2D6 Inhibition. Pharmaceutics. 2021 Jan 23;13(2):148. doi: 10.3390/pharmaceutics13020148.
5. Edinoff AN, Fort JM, Woo JJ, Causey CD, Burroughs CR, Cornett EM, Kaye AM, Kaye AD. Selective Serotonin Reuptake Inhibitors and Clozapine: Clinically Relevant Interactions and Considerations. Neurol Int. 2021 Sep 1;13(3):445-463. doi: 10.3390/neurolint13030044.
6. Wei A, Peng J, Gu Z, Li J. QTc prolongation and torsades de pointes due to a coadministration of fluoxetine and amiodarone in a patient with implantable cardioverter-defibrillator: Case report and review of the literature. Medicine (Baltimore). 2017 Dec;96(49):e9071. doi: 10.1097/MD.0000000000009071.
7. Spina, E., Barbieri, M. A., Cicala, G., Bruno, A., & de Leon, J. (2019). Clinically relevant drug interactions between newer antidepressants and oral anticoagulants. Expert Opinion on Drug Metabolism & Toxicology, 16(1), 31–44. https://doi.org/10.1080/17425255.2020.1700952
8. De Abajo, F.J., Montero, D., García Rodríguez, L.A. and Madurga, M. (2006), Antidepressants and Risk of Upper Gastrointestinal Bleeding. Basic & Clinical Pharmacology & Toxicology, 98: 304-310. https://doi.org/10.1111/j.1742-7843.2006.pto_303.x
9. Zaccara G, Franco V. Pharmacokinetic Interactions Between Antiseizure and Psychiatric Medications. Curr Neuropharmacol. 2023;21(8):1666-1690. doi: 10.2174/1570159X20666220524121645.
10. Park SH, Wackernah RC, Stimmel GL. Serotonin Syndrome: Is It a Reason to Avoid the Use of Tramadol With Antidepressants? Journal of Pharmacy Practice. 2014;27(1):71-78. doi:10.1177/0897190013504957
11. Simon LV, Torrico TJ, Keenaghan M. Serotonin Syndrome. [Updated 2024 Mar 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482377/
12. Oliva, V., Lippi, M., Paci, R., Del Fabro, L., Delvecchio, G., Brambilla, P., De Ronchi, D., Fanelli, G., & Serretti, A. (2021). Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 109, 110266. https://doi.org/10.1016/j.pnpbp.2021.110266
13. Fluoxetine and extrapyramidal side effects. (1995). American Journal of Psychiatry, 152(1), 122–125. https://doi.org/10.1176/ajp.152.1.122
14. Chen VC, Ng MH, Chiu WC, McIntyre RS, Lee Y, Lin TY, Weng JC, Chen PC, Hsu CY. Effects of selective serotonin reuptake inhibitors on glaucoma: A nationwide population-based study. PLoS One. 2017 Mar 3;12(3):e0173005. doi: 10.1371/journal.pone.0173005.
15. Gabriel M, Sharma V. Antidepressant discontinuation syndrome. CMAJ. 2017 May 29;189(21):E747. doi: 10.1503/cmaj.160991.
16. Edinoff AN, Raveendran K, Colon MA, Thomas BH, Trettin KA, Hunt GW, Kaye AM, Cornett EM, Kaye AD. Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review. Health Psychol Res. 2022 Nov 3;10(4):39580. doi: 10.52965/001c.39580.
17. Fluoxetine: MedlinePlus drug information. (n.d.). https://medlineplus.gov/druginfo/meds/a689006.html
18. Mother To Baby | Fact Sheets [Internet]. Brentwood (TN): Organization of Teratology Information Specialists (OTIS); 1994-. Fluoxetine (Prozac®) 2022 Oct. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582711/
19. Brumbaugh JE, Ball CT, Crook JE, Stoppel CJ, Carey WA, Bobo WV. Poor Neonatal Adaptation After Antidepressant Exposure During the Third Trimester in a Geographically Defined Cohort. Mayo Clin Proc Innov Qual Outcomes. 2023 Mar 7;7(2):127-139. doi: 10.1016/j.mayocpiqo.2023.02.002.