Iloperidone and Suvorexant interaction
Iloperidone and Suvorexant: both prescribing labels describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.
Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.
What the FDA labels say
From the Iloperidone (FANAPT) label · effective 2026-05-06
The dose of FANAPT should be reduced in patients co-administered a strong CYP2D6 or CYP3A4 inhibitor.
Strong CYP3A4 Inhibitors Clinical Impact Co-administration of ketoconazole with iloperidone, increased the AUC of iloperidone and its metabolites P88 and P95 by 57%, 55%, and 35%, respectively [see Clinical Pharmacology (12.3) ] .
Intervention Reduce the dose of FANAPT by one-half when administered with strong CYP3A4 inhibitors.
When the CYP3A4 inhibitor is withdrawn from the combination therapy, the FANAPT dose should be returned to the previous level [see Dosage and Administration (2.4) ] .
Concomitant use of Strong CYP2D6 and Strong CYP3A4 Inhibitors Clinical Impact Coadministration of iloperidone with paroxetine and ketoconazole resulted in a 1.4- fold increase in steady-state concentrations of iloperidone and its metabolite P88 and a 1.4- fold decrease in the P95 in the presence of paroxetine [see Clinical Pharmacology (12.3) ] .
From the Suvorexant (BELSOMRA) label · effective 2025-03-10
CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ).
Prescribers should monitor for somnolence and CNS depressant effects, but impairment can occur in the absence of symptoms, and may not be reliably detected by ordinary clinical exam (i.e., less than formal testing of daytime wakefulness and/or psychomotor performance).
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.
Dosage adjustments of BELSOMRA and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects.
The risk of next-day impairment, including impaired driving, is increased if BELSOMRA is taken with less than a full night of sleep remaining, if a higher than the recommended dose is taken, if co-administered with other CNS depressants, or if co-administered with other drugs that increase blood levels of BELSOMRA.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.