Learn about Caplyta (lumateperone) drug interactions — which medications to avoid, which require dose changes, and what to tell your doctor.
Caplyta (lumateperone) is processed in your body primarily by a liver enzyme called CYP3A4. Many common medications, supplements, and even foods affect this same enzyme — which means they can change how much Caplyta is in your system at any given time.
Too much Caplyta in your body can increase the risk of side effects. Too little can make the medication stop working. That's why understanding drug interactions is so important.
This guide covers the major interactions you need to know about — in plain language.
These medications slow down the enzyme that breaks down Caplyta, causing it to build up in your body. If you take any of these, your doctor should lower your Caplyta dose to 10.5 mg daily:
There are other strong CYP3A4 inhibitors as well. Always tell your doctor about every medication you take so they can check for interactions.
These medications have a moderate effect on the same enzyme. Your doctor should reduce your Caplyta dose to 21 mg daily if you take:
These medications speed up the enzyme that breaks down Caplyta, potentially making it ineffective. Using them with Caplyta is contraindicated (not allowed):
Important: St. John's Wort is available over the counter, and many people don't think of it as a "real" medication. But it's a strong CYP3A4 inducer and can make Caplyta stop working. If you're taking St. John's Wort, tell your doctor before starting Caplyta.
Caplyta has some serotonin activity, so combining it with other serotonergic drugs increases the risk of a dangerous condition called serotonin syndrome. Symptoms include agitation, rapid heartbeat, high temperature, muscle twitching, and loss of coordination.
Medications that increase serotonin include:
This doesn't mean you can't take Caplyta with an SSRI or SNRI — in fact, Caplyta is FDA-approved as an add-on to antidepressants for MDD. But your doctor needs to monitor you closely for signs of serotonin syndrome, especially when starting or increasing doses.
Taking Caplyta with serotonergic drugs also increases the risk of hyponatremia (dangerously low sodium levels), especially in elderly patients.
Caplyta can cause drowsiness on its own. Combining it with other medications that make you sleepy can increase this effect significantly:
If you take any of these with Caplyta, be extra cautious about driving, operating machinery, or doing anything that requires alertness.
Caplyta can lower blood pressure, especially when you stand up quickly (orthostatic hypotension). Taking it with blood pressure medications may increase this effect. Tell your doctor if you take:
Combining Caplyta with drugs that have anticholinergic effects can worsen side effects like dry mouth, constipation, blurred vision, and urinary retention. Common anticholinergic medications include:
Grapefruit inhibits CYP3A4, the same enzyme that breaks down Caplyta. Drinking grapefruit juice or eating grapefruit while taking Caplyta may increase drug levels in your body, raising the risk of side effects. Ask your doctor whether you need to avoid grapefruit entirely.
Alcohol adds to Caplyta's sedating effects and can worsen dizziness and drowsiness. It's best to avoid or strictly limit alcohol while taking Caplyta.
Before starting Caplyta, give your doctor a complete list of:
Don't assume something "doesn't count" because it's available without a prescription. Many OTC products and supplements interact with Caplyta.
You focus on staying healthy. We'll handle the rest.
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