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Drug Interactions between buprenorphine and dofetilide

This report displays the potential drug interactions for the following 2 drugs:

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Moderate

buprenorphine dofetilide

Applies to: buprenorphine and dofetilide

GENERALLY AVOID: Buprenorphine administered transdermally at a higher than recommended dosage has been associated with prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In healthy volunteers, there was no difference in the effect of buprenorphine 10 mcg/hr administered transdermally on the QT interval compared to placebo. However, buprenorphine 40 mcg/hr (twice the maximum recommended dosage) was associated with a mean prolongation of the QT interval of 5.9 msec compared to placebo. Buprenorphine 20 mcg/hr was not studied. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: According to the product labeling, use of buprenorphine transdermal films should be avoided in patients treated with class IA (e.g., disopyramide, quinidine, procainamide) or class III (e.g., amiodarone, dofetilide, sotalol) antiarrhythmic agents. A dosage of 20 mcg/hr should not be exceeded in patients receiving the buprenorphine transdermal system. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

References

  1. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  2. "Product Information. Butrans (buprenorphine)." Purdue Pharma LP (2010):

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Drug and food interactions

Major

buprenorphine food

Applies to: buprenorphine

GENERALLY AVOID: 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. Reported cases have primarily occurred in the setting of buprenorphine maintenance treatment for opiate addiction, and many, but not all, involved abuse or misuse of buprenorphine including intravenous self-injection. The mechanism of interaction probably involves some degree of additive pharmacologic effects. Preclinical studies also suggest that benzodiazepines can alter the usual ceiling effect on buprenorphine-induced respiratory depression and render the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Coadministration of buprenorphine with some CNS depressants such as alcohol, benzodiazepines, and phenothiazines may also increase the risk of hypotension.

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. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

References

  1. "Product Information. Suboxone (buprenorphine-naloxone)." Reckitt and Colman Pharmaceuticals Inc (2002):
  2. Kilicarslan T, Sellers EM "Lack of interaction of buprenorphine with flunitrazepam metabolism." Am J Psychiatry 157 (2000): 1164-6
  3. Reynaud M, Petit G, Potard D, Courty P "Six deaths linked to concomitant use of buprenorphine and benzodiazepines." Addiction 93 (1998): 1385-92
  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. 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
  6. Kintz P "A new series of 13 buprenorphine-related deaths." Clin Biochem 35 (2002): 513-6
  7. Martin HA "The possible consequences of combining lorazepam and buprenorphine/naloxone: a case review." J Emerg Nurs 37 (2011): 200-2
  8. 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
  9. 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 http://www.ncbi.nlm.nih.gov/books/NBK64245/" (2013):
  10. 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
  11. Ferrant O, Papin F, Clin B, et al. "Fatal poisoning due to snorting buprenorphine and alcohol consumption." Forensic Sci Int 204 (2011): e8-11
  12. 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
  13. Kintz P "Deaths involving buprenorphine: a compendium of French cases." Forensic Sci Int 121 (2001): 65-9
  14. Sekar M, Mimpriss TJ "Buprenorphine, benzodiazepines and prolonged respiratory depression." Anaesthesia 42 (1987): 567-8
  15. 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
  16. 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. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM518672.pdf" (2016):
View all 16 references

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Minor

dofetilide food

Applies to: dofetilide

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.

References

  1. "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals PROD (2001):

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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