Buprenorphine and naloxone and Lofexidine interaction
Buprenorphine and naloxone 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.
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
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.
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.
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.
Use in conjunction with a comprehensive management program for treatment of opioid use disorder and inform patients and caregivers of increased risk of overdose.
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.
From the Buprenorphine and naloxone label · effective 2026-06-16
Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets [see Warnings and Precautions (5.3) , Drug Interactions (7) ] .
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of buprenorphine and benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids) increases…
In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient's buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use.
Clinically Significant Drug Interactions with Buprenorphine and Naloxone Sublingual Tablets Benzodiazepines or other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound…
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Open in the checkerNot 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.