Hydrocodone and chlorpheniramine and Zaleplon interaction

Hydrocodone and chlorpheniramine and Zaleplon: 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 Zaleplon label · effective 2025-10-08

Major

The use of zaleplon with other sedative-hypnotics at bedtime or the middle of the night is not recommended (see ).

Warningsby drug classView label on DailyMed
Moderate

Post-marketing reports have shown that complex sleep behaviors may occur with zaleplon alone at recommended dosages, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants.

Warningsby drug classView label on DailyMed
Moderate

Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.

Warningsby drug classView label on DailyMed
Moderate

Dosage adjustments of zaleplon and of other concomitant CNS depressants may be necessary when zaleplon is administered with such agents because of the potentially additive effects.

Warningsby drug classView label on DailyMed
Moderate

The risk of next-day psychomotor impairment, including impaired driving, is increased if zaleplon is taken with less than a full night of sleep remaining (7 to 8 hours); if a higher than the recommended dose is taken; if coadministered with other CNS depressants or alcohol; or if coadministered with other drugs that increase the blood levels of zaleplon.

Warningsby drug classView label on DailyMed

From the Hydrocodone and chlorpheniramine (Hydrocodone Polistirex and Chlorpheniramine Polistirex extended-release) label · effective 2025-06-26

Major

…ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;…

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

Avoid the use of Hydrocodone Polistirex and Chlorpheniramine Polistirex in patients taking benzodiazepines, other CNS depressants, or alcohol [ see Warning and Precautions (5.8) , Drug Interactions (7.5) ].

Boxed warningby drug classView label on DailyMed
Major

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

Avoid concurrent use of Hydrocodone Polistirex and Chlorpheniramine Polistirex with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur [ see Warnings and Precautions (5.8) ].

Warnings and 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.