Eszopiclone and Hydroxyzine interaction

Eszopiclone and Hydroxyzine: 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 Eszopiclone (Lunesta) label · effective 2025-01-08

Major

The use of LUNESTA with other sedative-hypnotics at bedtime or the middle of the night is not recommended.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risk increases with dose and use with other CNS depressants and alcohol.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Post-marketing reports have shown that complex sleep behaviors may occur with LUNESTA alone at recommended dosages, with or without the concomitant use of alcohol or other CNS depressants [see Drug Interactions ( 7.1 )] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

Additive effects occur with concomitant use of other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use.

Warnings and precautionsby drug classView label on DailyMed
Moderate

…psychomotor impairment is increased if LUNESTA is taken with less than a full night of sleep remaining (7- to 8 hours); if higher than the recommended dose is taken; if coadministered with other CNS depressants; or coadministered with other drugs that increase the blood levels of eszopiclone [see Dosage and Administration ( 2.3 ) and Clinical Studies ( 14.3 )].

Warnings and precautionsby drug classView label on DailyMed

From the Hydroxyzine label · effective 2025-10-31

Major

Rarely, cardiac arrests and death have been reported in association with the combined use of hydroxyzine hydrochloride intramuscularly and other CNS depressants.

Precautionsby drug classView label on DailyMed
Moderate

PRECAUTIONS THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS SUCH AS NARCOTICS, BARBITURATES AND ALCOHOL.

Precautionsby drug classView label on DailyMed
Moderate

Therefore, when central nervous system depressants are administered concomitantly with hydroxyzine their dosage should be reduced up to 50 percent.

Precautionsby drug classView label on DailyMed
Moderate

The efficacy of hydroxyzine as adjunctive pre- and postoperative sedative medication has also been well established, especially as regards its ability to allay anxiety, control emesis, and reduce the amount of narcotic required.

Precautionsby drug classView label on DailyMed

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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.