From the FDA Drug Label
Fluvoxamine is a known potent inhibitor of CYP1A2 and also inhibits CYP3A4, CYP2C9, and CYP2C19. The available knowledge concerning the relationship of fluvoxamine and the CYP450-enzyme system has been obtained mostly from pharmacokinetic interaction studies conducted in healthy volunteers, but some preliminary in vitro data are also available Based on a finding of substantial interactions of fluvoxamine with certain of these drugs (see later parts of this section and also WARNINGS for details) and limited in vitro data for the 3A4 isozyme, it appears that fluvoxamine inhibits the following isozymes that are known to be involved in the metabolism of the listed drugs: 1A2,2C9,3A4,2C19
- Fluvoxamine is an example of an antidepressant with CYP1A2 inhibition 1.
- Other antidepressants that may have CYP1A2 inhibition properties are not explicitly mentioned in the provided drug labels.
- Fluvoxamine is a potent inhibitor of CYP1A2 and other isozymes, which can lead to significant interactions with other drugs 1.
From the Research
Antidepressants that inhibit CYP1A2 include fluvoxamine, which is the strongest inhibitor, and other medications such as fluoxetine and paroxetine, although to a lesser extent. When considering the inhibition of CYP1A2 by antidepressants, it's crucial to prioritize the most recent and highest quality evidence to minimize risks associated with drug interactions, particularly in terms of morbidity, mortality, and quality of life. The evidence from 2 highlights that fluvoxamine is a potent CYP1A2 inhibitor, which can significantly increase the blood levels of medications metabolized by this enzyme, such as clozapine, olanzapine, theophylline, and caffeine. Key points to consider include:
- Fluvoxamine's potent inhibition of CYP1A2, which necessitates careful dose adjustment of co-administered medications that are substrates of this enzyme.
- The potential for fluoxetine and paroxetine to also inhibit CYP1A2, albeit less potently than fluvoxamine, as noted in 3.
- The importance of monitoring patients for side effects when these antidepressants are combined with CYP1A2 substrates and adjusting doses as necessary to prevent toxicity.
- The persistence of the inhibitory effect for days to weeks after discontinuation of these antidepressants due to their half-lives and the presence of active metabolites, as discussed in 4. Given the potential for significant drug interactions, clinicians should be cautious when prescribing these antidepressants, especially in patients taking medications that are CYP1A2 substrates, and should consider the pharmacokinetic properties of each SSRI, as outlined in 5 and 6, to minimize risks and optimize patient outcomes.