Acetaminophen and codeine and Buprenorphine and naloxone interaction
Acetaminophen and codeine and Buprenorphine and naloxone: 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 Acetaminophen and codeine (ACETAMINOPHEN AND CODEINE PHOSPHATE) label · effective 2026-01-22
Consider recommending or prescribing an opioid overdose reversal agent ( see WARNINGS, Life-Threatening Respiratory Depression ; DOSAGE AND ADMINISTRATION, Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose ).
If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent ( see WARNINGS, Life-Threatening Respiratory Depression ; DOSAGE AND ADMINISTRATION , Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose ).
Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including acetaminophen and codeine phosphate tablets.
If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
…ACETAMINOPHEN AND CODEINE PHOSPHATE TABLETS Addiction, Abuse, and Misuse Because the use of acetaminophen and codeine phosphate tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of…
From the Buprenorphine and naloxone label · effective 2026-06-16
Addiction, Abuse, and Misuse: Buprenorphine can be abused in a similar manner to other opioids.
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.
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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.