FLUOXETINE HCL Drug Interactions
Also known as: Fluoxetine HCL
FLUOXETINE HCL (brand name: Fluoxetine HCL) is a SSRIs. Fluoxetine is indicated for the treatment of: Acute and maintenance treatment of Major Depressive Disorder [see CLINICAL STUDIES (14.1)] . Acute and maintenance treatment of obsessions and compulsions in patients with Obsessive Compulsive Disorder (OCD) [see CLINICAL STUDIES (14.2)] . Acute and…FLUOXETINE HCL has 14 documented drug interactions in our database, including 0 contraindicated, 4 major, 6 moderate, and 4 minor interactions.
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Contraindicated
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Major
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Moderate
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Minor
Concomitant use of nebivolol and fluoxetine can significantly increase nebivolol plasma concentrations, leading to enhanced beta-blockade effects. This can manifest as severe bradycardia, hypotension, and potentially heart block, increasing the risk of cardiovascular adverse events.
Mechanism
Fluoxetine is a potent inhibitor of the cytochrome P450 2D6 (CYP2D6) enzyme. Nebivolol is primarily metabolized by CYP2D6, so fluoxetine inhibits its metabolism, leading to elevated systemic exposure to nebivolol.
Clinical Management
Avoid concomitant use if possible. If co-administration is necessary, closely monitor the patient for signs and symptoms of excessive beta-blockade (e.g., bradycardia, hypotension). A significant dose reduction of nebivolol may be required, or consider an alternative beta-blocker that is not primarily metabolized by CYP2D6 (e.g., atenolol, bisoprolol, nadolol) or an antidepressant with minimal CYP2D6 inhibition (e.g., sertraline, escitalopram).
Fluoxetine, a potent CYP2D6 inhibitor, can significantly increase plasma concentrations of metoprolol, a CYP2D6-metabolized beta-blocker. This can lead to an increased risk of adverse effects such as severe bradycardia, hypotension, and heart block.
Mechanism
Fluoxetine inhibits the cytochrome P450 2D6 (CYP2D6) enzyme, which is primarily responsible for the metabolism of metoprolol. This pharmacokinetic interaction reduces metoprolol clearance, leading to higher systemic exposure.
Clinical Management
Avoid co-administration if possible. If concomitant use is necessary, closely monitor heart rate, blood pressure, and for signs of beta-blocker toxicity (e.g., bradycardia, dizziness, fatigue). A significant reduction in metoprolol dosage may be required, or consider switching to a beta-blocker not primarily metabolized by CYP2D6 (e.g., atenolol, bisoprolol, nadolol) or an antidepressant with minimal CYP2D6 inhibition (e.g., sertraline, escitalopram).
Fluoxetine, a potent CYP2D6 inhibitor, can significantly increase plasma concentrations of propranolol, a beta-blocker primarily metabolized by CYP2D6. This interaction can lead to enhanced beta-blockade effects, manifesting as severe bradycardia, hypotension, or heart block.
Mechanism
Fluoxetine inhibits the cytochrome P450 2D6 (CYP2D6) enzyme, which is a major metabolic pathway for propranolol. This inhibition reduces the clearance of propranolol, leading to elevated systemic exposure and increased pharmacodynamic effects.
Clinical Management
If co-administration is necessary, a significant reduction in propranolol dosage may be required, along with close monitoring of heart rate, blood pressure, and cardiac rhythm for signs of excessive beta-blockade. Consider using an alternative antidepressant with minimal CYP2D6 inhibition (e.g., sertraline, escitalopram) or a beta-blocker primarily cleared renally (e.g., atenolol, nadolol) to avoid this interaction.
The co-administration of timolol, a beta-blocker primarily metabolized by CYP2D6, with fluoxetine, a potent CYP2D6 inhibitor, can significantly increase timolol plasma concentrations. This interaction can lead to exaggerated beta-blockade effects, including severe bradycardia, hypotension, and heart block, particularly given timolol's systemic absorption even when administered topically.
Mechanism
Fluoxetine is a potent inhibitor of the cytochrome P450 2D6 (CYP2D6) enzyme. Timolol is primarily metabolized by CYP2D6, so fluoxetine inhibits the metabolism of timolol, leading to decreased clearance and increased systemic exposure of timolol.
Clinical Management
Avoid concurrent use if possible. If co-administration is necessary, closely monitor the patient for signs and symptoms of excessive beta-blockade (e.g., bradycardia, hypotension, dizziness, fatigue). Consider using an alternative antidepressant with minimal CYP2D6 inhibition (e.g., sertraline, escitalopram) or a beta-blocker primarily cleared renally (e.g., atenolol, bisoprolol, nadolol) or with less CYP2D6 involvement.
Combining sertraline and fluoxetine, both selective serotonin reuptake inhibitors (SSRIs), significantly increases the risk of serotonin syndrome. Patients may experience symptoms such as agitation, confusion, sweating, tremor, and hyperreflexia, which can range from mild to life-threatening.
Mechanism
Both sertraline and fluoxetine increase synaptic serotonin concentrations by inhibiting serotonin reuptake in the central nervous system. When used concurrently, their additive serotonergic effects can lead to excessive stimulation of serotonin receptors.
Clinical Management
Concurrent use should generally be avoided due to the increased risk of serotonin syndrome. If co-administration is deemed necessary, close monitoring for signs and symptoms of serotonin syndrome is crucial, and lower doses of one or both agents may be considered. Patients should be educated on the symptoms of serotonin syndrome and advised to seek immediate medical attention if they occur.
Fluoxetine inhibits CYP2D6, increasing carvedilol plasma levels and potentially causing excessive beta-blockade.
Mechanism
Carvedilol is primarily metabolized by CYP2D6. Fluoxetine's CYP2D6 inhibition increases carvedilol AUC by up to 77%.
Clinical Management
Monitor for signs of excessive beta-blockade (bradycardia, hypotension). Consider dose reduction of carvedilol.
Fluoxetine can increase pindolol plasma levels, potentially leading to enhanced beta-blockade effects such as bradycardia, hypotension, and heart block. This interaction is due to fluoxetine's potent inhibition of CYP2D6, an enzyme involved in pindolol metabolism.
Mechanism
Fluoxetine is a potent inhibitor of cytochrome P450 2D6 (CYP2D6). Pindolol is partially metabolized by CYP2D6, so fluoxetine can decrease its metabolism and increase its systemic exposure.
Clinical Management
Monitor patients closely for signs of increased beta-blockade, including bradycardia, hypotension, and dizziness, especially when initiating or discontinuing fluoxetine or changing its dose. Consider a dose reduction of pindolol or using an alternative antidepressant with less CYP2D6 inhibitory potential, such as sertraline or escitalopram, if close monitoring is not feasible.
Fluoxetine significantly increases metoprolol plasma levels through CYP2D6 inhibition, increasing the risk of bradycardia and heart block.
Mechanism
Fluoxetine is a potent CYP2D6 inhibitor. Metoprolol is primarily metabolized by CYP2D6; inhibition increases metoprolol AUC by 3–5 fold.
Clinical Management
Monitor heart rate and blood pressure. Reduce metoprolol dose if bradycardia occurs. Consider using atenolol (not CYP2D6 substrate) as an alternative.
Fluoxetine, a potent CYP2D6 inhibitor, can increase plasma concentrations of acebutolol, which is partially metabolized by CYP2D6. This interaction may enhance the pharmacologic effects of acebutolol, potentially leading to increased risk of bradycardia, hypotension, or heart block.
Mechanism
Fluoxetine inhibits cytochrome P450 2D6 (CYP2D6), an enzyme involved in the metabolism of acebutolol. This inhibition reduces acebutolol clearance, leading to higher systemic exposure.
Clinical Management
Monitor patients closely for signs and symptoms of beta-blockade, such as bradycardia, hypotension, and dizziness, especially when initiating or adjusting fluoxetine. Consider using an alternative antidepressant with minimal CYP2D6 inhibition (e.g., sertraline, escitalopram) or a beta-blocker primarily cleared renally (e.g., atenolol, nadolol) if close monitoring is not feasible or if adverse effects occur.
Combining fluoxetine and paroxetine, both selective serotonin reuptake inhibitors (SSRIs), can lead to an increased risk of serotonin syndrome and additive serotonergic side effects. Patients may experience symptoms such as agitation, confusion, sweating, tremor, and diarrhea.
Mechanism
Both fluoxetine and paroxetine increase serotonin levels in the central nervous system by inhibiting its reuptake. Concurrent use leads to an additive effect on serotonin concentrations, potentially causing excessive serotonergic activity.
Clinical Management
Coadministration of fluoxetine and paroxetine is generally not recommended due to the increased risk of serotonin syndrome and other adverse effects. If combination therapy is deemed necessary, close monitoring for signs and symptoms of serotonin syndrome is crucial, and dose adjustments of one or both agents may be required. Consider alternative antidepressant strategies if possible.
The interaction between atenolol and fluoxetine is generally not considered clinically significant due to atenolol's primary renal clearance. Unlike other beta-blockers, atenolol is minimally affected by CYP2D6 inhibition, which is the primary mechanism of interaction for fluoxetine with other beta-blockers.
Mechanism
Fluoxetine is a potent inhibitor of CYP2D6. However, atenolol is primarily eliminated by renal excretion and undergoes minimal hepatic metabolism, including via CYP2D6. Therefore, fluoxetine's inhibitory effect on CYP2D6 has little to no impact on atenolol's pharmacokinetics.
Clinical Management
No specific dose adjustments or enhanced monitoring are typically required when co-administering atenolol and fluoxetine. Clinicians should always monitor patients for expected therapeutic effects and potential side effects of both medications, as with any polypharmacy.
The interaction between nadolol and fluoxetine is considered minor. While fluoxetine is a potent CYP2D6 inhibitor, nadolol is primarily eliminated renally with minimal CYP2D6 metabolism, making a significant pharmacokinetic interaction unlikely.
Mechanism
Fluoxetine is a potent inhibitor of CYP2D6. However, nadolol is predominantly cleared by the kidneys and is not significantly metabolized by CYP2D6, thus its plasma levels are not expected to be significantly altered by fluoxetine.
Clinical Management
No specific dose adjustments for nadolol are typically required when co-administered with fluoxetine. Monitor patients for additive pharmacodynamic effects such as excessive bradycardia or hypotension, especially if they have pre-existing cardiac conditions or are on other medications that lower heart rate or blood pressure.
Labetalol is primarily metabolized by CYP2D6, but it is not considered a potent substrate like metoprolol or propranolol. Fluoxetine is a potent CYP2D6 inhibitor, but the clinical significance of this interaction with labetalol is generally considered low.
Mechanism
Fluoxetine, a potent CYP2D6 inhibitor, can theoretically decrease the metabolism of labetalol, which is partially metabolized by CYP2D6. This could lead to increased labetalol plasma concentrations.
Clinical Management
Monitor for signs of increased beta-blockade, such as bradycardia or hypotension, especially when initiating or discontinuing fluoxetine in patients on labetalol. Dose adjustments of labetalol are usually not necessary, but clinical monitoring is prudent.
The interaction between bisoprolol and fluoxetine is generally considered minor. While fluoxetine is a potent CYP2D6 inhibitor, bisoprolol is primarily renally cleared, minimizing the pharmacokinetic interaction risk. However, both drugs can independently cause bradycardia, so additive pharmacodynamic effects are possible.
Mechanism
Fluoxetine is a potent inhibitor of CYP2D6. However, bisoprolol is primarily eliminated renally with minimal CYP2D6 metabolism, thus significant pharmacokinetic interaction via this pathway is unlikely. Both drugs can exert bradycardic effects, leading to potential additive pharmacodynamic effects.
Clinical Management
Generally, no specific dose adjustments are required for bisoprolol when co-administered with fluoxetine due to the minimal pharmacokinetic interaction. However, clinicians should monitor patients for signs of excessive bradycardia or hypotension, especially when initiating or significantly changing fluoxetine dosage. If such symptoms occur, consider reducing the bisoprolol dose.
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