Basic Information
ID DDInter251 and DDInter239
Interaction Concomitant use of buprenorphine with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may increase the risk of buprenorphine overdose, severe respiratory depression, coma, and death.
Management The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. Extreme caution is advised when prescribing buprenorphine to patients who are addicted to opioids and also abusing benzodiazepines or alcohol. Due to potential risk of overdose and death, dependence on sedative-hypnotics such as benzodiazepines or alcohol is considered a relative contraindication for office-based buprenorphine treatment of opioid addiction.
References [1] Sekar M, Mimpriss TJ "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia 42 (1987): 567-8 [2] Pirnay S, Borron SW, Giudicelli CP, Tourneau J, Baud FJ, Ricordel I "A critical review of the causes of death among post-morten toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths." Addiction 99 (2004): 978-88 [3] Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ "Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes." Drug Alcohol Depend 132 (2013): 580-6 [4] Tracqui A, Kintz P, Ludes B "Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities." J Anal Toxicol 22 (1998): 430-4 [5] Kintz P "A new series of 13 buprenorphine-related deaths." Clin Biochem 35 (2002): 513-6 [6] Kilicarslan T, Sellers EM "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry 157 (2000): 1164-6 [7] Martin HA "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs 37 (2011): 200-2 [8] Reynaud M, Tracqui A, Petit G, Potard D, Courty P "Six deaths linked to misuse of buprenorphine-benzodiazepine combinations." Am J Psychiatry 155 (1998): 448-9 [9] "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc, Richmond, VA. [10] US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Available from: URL: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf." ([2016, Aug 31]): [11] Hakkinen M, Launiainen T, Vuori E, Ojanpera I "Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning." Eur J Clin Pharmacol 68 (2012): 301-9 [12] Substance Abuse and Mental Health Services Administration (US) "Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series, No. 40 Available from: URL: http://www.ncbi.nlm.nih.gov/books/NBK64245/" ([2004]): [13] Ferrant O, Papin F, Clin B, et al "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int 204 (2011): e8-11 [14] Kintz P "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int 121 (2001): 65-9 [15] Reynaud M, Petit G, Potard D, Courty P "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction 93 (1998): 1385-92 [16] Gueye PN, Borron SW, Risede P, et al "Buprenorphine and midazolalm act in combination to depress respiration in rats." Toxicol Sci 65 (2002): 107-14 [17] "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ. [18] Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990): [19] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7 [20] "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
Alternative for Buprenorphine N07B
Disulfiram Nicotine Nalmefene Acamprosate Varenicline Naltrexone

N02A
Ibuprofen Acetaminophen Naloxone Acetylsalicylic acid Celecoxib Naltrexone
Alternative for Brivaracetam -
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.