Fluoxetine: Difference between revisions
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MDElliottMD (talk | contribs) Link legal-status field to the USLegal: namespace |
MDElliottMD (talk | contribs) Add SSRI suicidality boxed warning (monitoring + counseling) and MAOI contraindication / serotonin-syndrome interactions; reconcile half-life to FDA label. Parser pharm-audit fix, mark-greenlit, servops-applied. |
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| onset = | | onset = | ||
| duration = Very long | | duration = Very long | ||
| halflife = | | halflife = 1-3 days acute, 4-6 days chronic; 4-16 days for norfluoxetine<ref name="prozac-label"/> | ||
| bioavailability = 70–90% (oral) | | bioavailability = 70–90% (oral) | ||
| pregnancy = Category C<ref name="lactmed">S0</ref> | | pregnancy = Category C<ref name="lactmed">S0</ref> | ||
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| pk_absorption = 70–90%<ref name="statpearls">S3</ref> oral bioavailability. | | pk_absorption = 70–90%<ref name="statpearls">S3</ref> oral bioavailability. | ||
| pk_distribution = Fluoxetine has plasma protein binding of approximately 94.5%, bound to albumin and alpha-1 glycoprotein. Fluoxetine readily crosses the blood–brain barrier, with a brain-to-plasma ratio of 2.6:1 in humans. The volume of distribution (Vd) of fluoxetine and its metabolite ranges between 20 to 42 L/kg. Some studies report that fluoxetine has the maximum volume of distribution (Vd) of any SSRI (between 14 and 100 L/kg).<ref name="statpearls"/> | | pk_distribution = Fluoxetine has plasma protein binding of approximately 94.5%, bound to albumin and alpha-1 glycoprotein. Fluoxetine readily crosses the blood–brain barrier, with a brain-to-plasma ratio of 2.6:1 in humans. The volume of distribution (Vd) of fluoxetine and its metabolite ranges between 20 to 42 L/kg. Some studies report that fluoxetine has the maximum volume of distribution (Vd) of any SSRI (between 14 and 100 L/kg).<ref name="statpearls"/> | ||
| pk_metabolism = Fluoxetine's active metabolite is norfluoxetine, produced when the cytochrome P450 enzyme ([[Enzyme:CYP2D6|CYP2D6]]) acts on it. Prescribers must remember that fluoxetine has several med-med interactions due to its metabolism through the CYP2D6 isoenzyme. Additionally, norfluoxetine can have an inhibitory effect on [[Enzyme:CYP3A4|CYP3A4]]. Fluoxetine has | | pk_metabolism = Fluoxetine's active metabolite is norfluoxetine, produced when the cytochrome P450 enzyme ([[Enzyme:CYP2D6|CYP2D6]]) acts on it. Prescribers must remember that fluoxetine has several med-med interactions due to its metabolism through the CYP2D6 isoenzyme. Additionally, norfluoxetine can have an inhibitory effect on [[Enzyme:CYP3A4|CYP3A4]]. Fluoxetine has an elimination half-life of 1 to 3 days after a single dose and 4 to 6 days with chronic dosing, and its active metabolite norfluoxetine has a half-life of 4 to 16 days.<ref name="prozac-label"/> Approximately 7% of individuals definitively exhibit poor metabolism of fluoxetine due to reduced activity of CYP2D6.<ref name="statpearls"/> | ||
| pk_elimination = | | pk_elimination = | ||
| pharmacodynamics = | | pharmacodynamics = | ||
| interactions = <pharmaInteractions/> | | interactions = <pharmaInteractions/> | ||
The clinically important interactions for prescribers: | |||
* '''MAO inhibitors: contraindicated.''' Combination with non-selective MAOIs (isocarboxazid, phenelzine, tranylcypromine), or with linezolid or intravenous methylene blue, can produce serotonin syndrome, which may be life-threatening. At least 14 days must elapse between stopping an MAOI and starting fluoxetine. Because of the long half-life of fluoxetine and its active metabolite norfluoxetine, at least 5 weeks must elapse between stopping fluoxetine and starting an MAOI.<ref name="prozac-label">U.S. Food and Drug Administration. Prozac (fluoxetine hydrochloride) prescribing information. NDA 018936.</ref> | |||
* '''Other serotonergic medicines: serotonin-syndrome risk.''' Triptans, tramadol, other SSRIs and SNRIs, lithium, and St John's wort raise serotonergic load; combine with caution and counsel on serotonin-syndrome symptoms. | |||
* '''Strong CYP2D6 inhibition.''' Fluoxetine is a strong CYP2D6 inhibitor and norfluoxetine inhibits CYP3A4, so levels of many CYP2D6 substrates rise (several tricyclics, some neuroleptics, metoprolol, atomoxetine; tamoxifen activation is blunted). Because of the long half-life, this effect persists for weeks after fluoxetine is stopped. | |||
| pregnancy_details = | | pregnancy_details = | ||
| monitoring = | | monitoring = '''Boxed warning: monitor closely for worsening mood, suicidal ideation, and behavioral activation,''' especially during the first weeks of treatment, with any dose change, and particularly in patients under age 25. No routine laboratory monitoring required. Because of fluoxetine's very long effective half-life, both therapeutic change and adverse effects (including activation or emergent suicidality) appear and resolve more slowly than with shorter-acting SSRIs. Watch for emergent manic or hypomanic symptoms throughout treatment and treat new rapid mood elevation, agitation, or pressured speech as a possible bipolar switch. | ||
| counseling = | | counseling = '''Before starting:''' screen for a personal or family history of bipolar disorder; fluoxetine, like all antidepressants, can precipitate a manic or mixed switch in susceptible patients. '''Boxed warning:''' counsel patients (and family members, where appropriate) about the increased risk of suicidal ideation and behavioral activation in patients under 25, and ask them to report promptly any worsening mood, intrusive thoughts of self-harm, agitation, irritability, or unusual behavioral changes, particularly in the first weeks of treatment and after any dose change. | ||
| anecdotes = <anecdote slug="2026-05-12" perspective="provider" author="MDElliottMD"> | | anecdotes = <anecdote slug="2026-05-12" perspective="provider" author="MDElliottMD"> | ||
Fluoxetine is great for getting off other SxRIs! Especially [[Venlafaxine|venlafaxine]] and [[Duloxetine|duloxetine]]. | Fluoxetine is great for getting off other SxRIs! Especially [[Venlafaxine|venlafaxine]] and [[Duloxetine|duloxetine]]. | ||