Clozapine and Phenobarbital interaction
Clozapine and Phenobarbital: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Clozapine (Clozaril) label · effective 2025-06-06
• Concomitant use of Strong CYP3A4 Inducers is not recommended.
However, concomitant use of CLOZARIL and strong CYP3A4 inducers is not recommended [see Dosage and Administration ( 2.7 )] .
• Discontinuation of CYP1A2 or CYP3A4 Inducers: Consider reducing CLOZARIL dose when CYP1A2 inducers (e.g., tobacco smoke) or CYP3A4 inducers (e.g., carbamazepine) are discontinued.
CYP1A2 and CYP3A4 Inducers Concomitant treatment with drugs that induce CYP1A2 or CYP3A4 can decrease the plasma concentration of clozapine, resulting in decreased effectiveness of CLOZARIL.
Consider reducing the CLOZARIL dosage when discontinuing coadministered enzyme inducers; because discontinuation of inducers can result in increased clozapine plasma levels and an increased risk of adverse reactions [see Dosage and Administration ( 2.7 )] .
From the Phenobarbital (SEZABY) label · effective 2025-12-23
CNS depressants: Closely monitor for sedation and respiratory depression.
Drugs that Prolong the QT Interval : Avoid concomitant use.
CNS Depressants Closely monitor for signs of sedation and respiratory depression with concomitant use of SEZABY with other CNS depressants, including opioids [see Warnings and Precautions (5.1)] .
QT Prolongation SEZABY may prolong the QT interval [see Clinical Pharmacology (12.2)] .
Drugs that Prolong QT Interval SEZABY may prolong the QT interval [see Warnings and Precautions (5.10) and Clinical Pharmacology (12.2)] .
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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.