Drug General Information (ID: DDIXY4EB06)
Drug Name			Buprenorphine		Drug Info		Dantrolene		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Analgesics				Muscle Relaxants
Structure

Mechanism of Buprenorphine-Dantrolene Interaction (Severity Level: Major)
Additive CNS depression effects Click to Show/Hide Mechanism Graph
Drug Name		Buprenorphine				Dantrolene
Mechanism		CNS depression effects				CNS depression effects
Key Mechanism Factor 1
		Factor Name		CNS depression effects
		Factor Description		CNS depressants are drugs that inhibit or suppress brain activity and can reduce mental and physical processes. Excessive CNS depression can lead to decreased heart rate, slow breathing (less than 10 breaths per minute), extreme confusion or loss of memory, nausea and vomiting, poor judgment, blue lips or fingertips, irritability and aggression, and clammy or cold skin.
Mechanism Description		Additive CNS depression effects by the combination of Buprenorphine and Dantrolene

Recommended Action
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. [PMID: 3592200]
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. [PMID: 15265095]
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. [PMID: 23688843]
4	Reynaud M, Petit G, Potard D, Courty P "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction 93 (1998): 1385-92. [PMID: 9926544]
5	Kintz P "A new series of 13 buprenorphine-related deaths." Clin Biochem 35 (2002): 513-6. [PMID: 12493578]
6	Kilicarslan T, Sellers EM "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry 157 (2000): 1164-6. [PMID: 10873929]
7	Product Information. Suboxone (buprenorphine-naloxone). Reckitt and Colman Pharmaceuticals Inc, Richmond, VA.
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. [PMID: 9501765]
9	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.".
10	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. [PMID: 21927835]
11	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. [PMID: 11752690]
12	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. [PMID: 9788517]
13	Martin HA "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs 37 (2011): 200-2. [PMID: 21397143]
14	Center for Substance Abuse Treatment.?Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2004. [PMID: 22514846]
15	Ferrant O, Papin F, Clin B, et al "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int 204 (2011): e8-11. [PMID: 20554411]
16	Kintz P "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int 121 (2001): 65-9. [PMID: 11516889]