Hydrocodone and chlorpheniramine and Lofexidine interaction

Hydrocodone and chlorpheniramine and Lofexidine: 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 Lofexidine label · effective 2026-07-22

Major

Increased Risk of Opioid Overdose after Opioid Discontinuation : Patients who complete opioid discontinuation are at an increased risk of fatal overdose should they resume opioid use.

Warnings and precautionsby drug classView label on DailyMed
Major

Patients who complete opioid discontinuation are likely to have a reduced tolerance to opioids and are at increased risk of fatal overdose should they resume opioid use.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs : Lofexidine tablets potentiates the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Use in conjunction with a comprehensive management program for treatment of opioid use disorder and inform patients and caregivers of increased risk of overdose.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Increased Risk of Central Nervous System Depression with Concomitant use of CNS Depressant Drugs Lofexidine tablets potentiates the CNS depressive effects of benzodiazepines and can also be expected to potentiate the CNS depressive effects of alcohol, barbiturates, and other sedating drugs.

Warnings and precautionsby 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.