Phenobarbital and Ramelteon interaction

Phenobarbital and Ramelteon: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Phenobarbital (SEZABY) label · effective 2025-12-23

Major

CNS depressants: Closely monitor for sedation and respiratory depression.

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Major

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)] .

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From the Ramelteon (Rozerem) label · effective 2026-04-15

Moderate

The use of alcohol and other CNS depressants may increase the risk of such behaviors.

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Moderate

Rifampin (strong CYP enzyme inducer): Decreases exposure to and effects of ramelteon.

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Moderate

Rifampin (strong CYP enzyme inducer) Administration of multiple doses of rifampin resulted in a mean decrease of approximately 80% in total exposure to ramelteon and metabolite M-II.

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Moderate

Efficacy may be reduced when ROZEREM is used in combination with strong CYP enzyme inducers such as rifampin [see Clinical Pharmacology (12.5) ] .

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Minor

In addition, in vitro data indicate that ramelteon does not cause false-positive results for benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines in two standard urine drug screening methods in vitro .

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Not 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.