Sertraline and Rilzabrutinib: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rilzabrutinib
Sertraline
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What's going on: Rilzabrutinib (Wayrilz) can slow down one of the liver enzymes (called CYP3A) that helps clear certain medicines from your body. Sertraline is partly broken down by that same enzyme, so taking both together may let a little more sertraline build up than usual.
In everyday terms, that could mean more of sertraline's usual side effects, like nausea, jitteriness, trouble sleeping, or an upset stomach. The good news is this is a manageable interaction. Your care team can keep an eye on how you're feeling and adjust your dose if needed. Please don't stop or change either medicine on your own, just let your pharmacist or doctor know you take both.
Mechanism: Rilzabrutinib is a moderate CYP3A inhibitor; sertraline is partially metabolized by CYP3A. Inhibition may reduce sertraline clearance, increasing exposure (AUC/Cmax) and the risk of dose-related adverse effects (GI upset, insomnia, tremor, serotonergic effects).
Magnitude/evidence: Theoretical for this pair. Probe data: rilzabrutinib 400 mg increased midazolam Cmax and AUC 2.2-fold (up to a predicted 3.0-fold at 400 mg BID in ITP). Sertraline effect not directly studied.
- Onset: unspecified
- Management: Monitor more frequently for sertraline-related adverse reactions; individualize/adjust sertraline dose as clinically indicated.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions
Interaction Deep Dive
When rilzabrutinib, a moderate CYP3A inhibitor, is given together with CYP3A substrates, exposure to those substrates may rise, raising the likelihood of adverse reactions associated with them. Monitor more frequently for adverse reactions from the concurrently given CYP3A substrate and adjust its dosage as needed. A drug interaction study in healthy participants showed that giving a single 400 mg dose of rilzabrutinib alongside midazolam (a sensitive CYP3A substrate) raised midazolam Cmax and AUC by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise as much as 3.0-fold when coadministered with rilzabrutinib 400 mg twice daily1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by rilzabrutinib
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is one clinicians manage routinely.
- Your team may watch you more closely for sertraline side effects such as nausea, restlessness, tremor, or sleep changes.
- Your sertraline dose may be adjusted and individualized by your prescriber if needed.
- Tell your pharmacist or doctor that you take both drugs, and report any new or worsening side effects.
No single fixed dose change applies to everyone, so your care team will tailor this to you.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study conducted in healthy participants, giving a single dose of rilzabrutinib 400 mg together with midazolam (a sensitive CYP3A substrate) raised the Cmax and AUC of midazolam by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise up to 3.0-fold when coadministered with 400 mg rilzabrutinib twice daily 1.
Common questions
Can I take Sertraline and Rilzabrutinib together?
Rilzabrutinib can raise sertraline levels by slowing its breakdown, so watch for more sertraline side effects; your care team can monitor you and adjust the dose if needed. Keep taking both as prescribed and report any new symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Rilzabrutinib interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Sertraline and Rilzabrutinib interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is one clinicians manage routinely. Your team may watch you more closely for sertraline side effects such as nausea, restlessness, tremor, or sleep changes. Your sertraline dose may be adjusted and individualized by your prescriber if needed. Tell your pharmacist or doctor that you take both drugs,… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sertraline or Rilzabrutinib need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (1)
- Product Information: WAYRILZ™ oral tablets, rilzabrutinib oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2025. DailyMed
Keep reading about Rilzabrutinib
Keep reading about Sertraline
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