What is the comparison between sertraline and fluvoxamine, specifically regarding CYP (Cytochrome P450) interactions?

CYP Interactions: Sertraline vs Fluvoxamine

Sertraline has a significantly more favorable CYP450 interaction profile than fluvoxamine and should be strongly preferred when drug-drug interactions are a concern. 1

Key CYP Enzyme Inhibition Differences

Sertraline's Limited CYP Inhibition

• Sertraline is only a moderate inhibitor of CYP2D6 and has minimal effects on other major CYP450 isoenzymes 1
• Sertraline is not a potent inhibitor of any CYP450 isoenzyme system, unlike other SSRIs 2
• Compared to other SSRIs, sertraline has less effect on the metabolism of other medications 1
• Sertraline demonstrates the most favorable profile for drug interactions among SSRIs, along with citalopram 3

Fluvoxamine's Extensive CYP Inhibition

• Fluvoxamine inhibits multiple CYP450 isoenzymes: CYP1A2, CYP2C19, CYP2C9, CYP3A4, and CYP2D6 1
• Fluvoxamine is a potent inhibitor of CYP1A2 and is the only SSRI with this property 4, 5, 6
• Fluvoxamine is a moderate inhibitor of CYP2C19 and CYP3A4 4, 5
• Fluvoxamine is a weak to moderate inhibitor of CYP2D6 7, 4

Clinical Implications for Drug Interactions

High-Risk Interactions with Fluvoxamine

• Fluvoxamine is contraindicated with tizanidine due to severe hypotension and sedation risk 7
• Fluvoxamine is contraindicated with alosetron due to serious adverse reaction risk 7
• Fluvoxamine causes clinically significant interactions with warfarin, theophylline, propranolol, alprazolam, and omeprazole 7
• Elevated carbamazepine levels and toxicity occur with fluvoxamine co-administration 7
• Elevated clozapine levels with increased seizure and orthostatic hypotension risk occur with fluvoxamine 7
• Fluvoxamine has greater potential for drug-drug interactions compared to other SSRIs 1

Lower-Risk Profile with Sertraline

• Sertraline does not significantly inhibit P450 3A4 activity and is unlikely to cause clinically significant interactions via this pathway 8
• Sertraline at lower doses has less prominent 2D6 inhibitory effects than other SSRIs 8
• Sertraline has low potential for pharmacokinetic drug interactions overall 2

Practical Prescribing Considerations

When to Choose Sertraline

• Choose sertraline for patients on multiple medications, particularly those metabolized by CYP1A2, CYP2C19, CYP2C9, or CYP3A4 1
• Select sertraline for patients taking warfarin, theophylline, or benzodiazepines to minimize interaction risk 7, 3
• Prefer sertraline in elderly patients or those with medical comorbidities requiring polypharmacy 2

When Fluvoxamine Requires Extreme Caution

• Avoid fluvoxamine in patients taking drugs with narrow therapeutic indices such as warfarin, theophylline, phenytoin, terfenadine, astemizole, cisapride, or pimozide 7
• If fluvoxamine must be used with CYP-metabolized drugs, monitor plasma levels and pharmacodynamic effects closely until steady-state is reached 7
• Never combine fluvoxamine with tizanidine or alosetron 7

Monitoring Requirements

For Sertraline

• Monitor plasma levels of co-administered drugs metabolized by CYP2D6 when using higher sertraline doses 8
• Consider dose reduction of CYP2D6-metabolized drugs when initiating sertraline 8
• When discontinuing sertraline, anticipate need for increased doses of co-administered CYP2D6 substrates 8

For Fluvoxamine

• Monitor plasma levels and clinical effects closely for all drugs metabolized by CYP1A2, CYP2C19, CYP2C9, CYP3A4, or CYP2D6 7
• Reduce doses of co-administered alprazolam or triazolam by 50% when starting fluvoxamine 1
• Monitor for clozapine-related seizures and orthostatic hypotension when combining with fluvoxamine 7

Common Pitfalls to Avoid

• Do not assume all SSRIs have equivalent drug interaction profiles—fluvoxamine's multi-enzyme inhibition creates substantially higher risk than sertraline 1, 3
• Do not overlook over-the-counter medications and supplements that may interact via CYP pathways with fluvoxamine 7
• Remember that approximately 7% of the population are CYP2D6 poor metabolizers, requiring extra caution even with sertraline 7
• Recognize that fluvoxamine's inhibition of CYP1A2 affects caffeine metabolism, potentially causing caffeine-related side effects 6