Lofexidine and Tramadol interaction

Lofexidine and Tramadol: 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

Risk of QT Prolongation : Lofexidine tablets prolong the QT interval.

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

From the Tramadol (Tramadol Hydrochloride Extended-Release) label · effective 2026-01-23

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

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

Reserve concomitant prescribing of Tramadol Hydrochloride Extended-Release Capsules and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) , Drug Interactions (7) ] .

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Tramadol Hydrochloride Extended-Release Capsules with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers,…

Warnings and precautionsby drug classView label on DailyMed
Major

Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7) ] .

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.