Open Access Open Access  Restricted Access Subscription or Fee Access

Decreased responsiveness to oxycodone: A case of a pharmacokinetic drug interaction?

Doreen Pon, PharmD, Joon Hwang, PharmD Candidate, Teresa Lo, PharmD Candidate, Carin Van Zyl, MD, FACEP


Concurrent administration of oxycodone and phenytoin may cause, through induction of CYP3A4 enzymes, decreased analgesic effects of oxycodone. However, no descriptions of this interaction exist. A patient who was on oxycodone for chronic back pain was admitted to the hospital. Five days after initiating fosphenytoin, the patient experienced a dramatic escalation in his pain and lack of response to oxycodone breakthrough doses. Changing oxycodone to hydromorphone resulted in significantly improved analgesia. Concurrent use of fosphenytoin and oxycodone may increase the conversion of oxycodone to inactive metabolites, resulting in decreased analgesia. This may be avoided using hydromorphone, morphine, or oxymorphone.


drug interaction, oxycodone, phenytoin, opioids, pain management

Full Text:



Lalovic B, Kharasch E, Hoffer C, et al.: Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther. 2006; 79: 461-479.

Soderberg-Löfdal KC, Andersson ML, Gustafsson LL: Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications. Drugs. 2013; 73: 533-543.

Phenytoin. Lexi-Drugs Online. Hudson, OH: Lexi-Comp, Inc., May 20, 2014.

Product Information. Oxycontin (Oxycodone Hydrochloride Extended Release Tablet). Stamford, CT: Purdue Pharma LP, April 2014.

Eisenberg E, Suzan E, Pud D: Opioid-induced hyperalgesia (OIH): A real clinical problem or just an experimental phenomenon? J Pain Symptom Manage. 2015; 49(3): 632-636.

Raffa RB, Pergolizzi JV: Opioid-induced hyperalgesia: Is it clinically relevant for the treatment of pain patients? Pain Manag Nurs. 2013; 14: e67-e83.

Lee M, Silverman S, Hansen H, et al.: A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011; 14: 145-161.

Overholser BR, Foster DR: Opioid pharmacokinetic drug-drug interactions. Am J Manag Care. 2011; 17(suppl): S276-S287.

Nieminen TH, Hagelberg NM, Saari TI, et al.: Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone. Anesthesiology. 2009; 110: 1371-1378.

Nieminen TH, Hagelberg NM, Saari TI, et al.: St John's Wort greatly reduces the concentrations of oral oxycodone. Eur J Pain. 2010; 14: 854-859.

Gong Z, Thomas D: Inadequate pain control with oxycodone in a patient taking Dilantin. Poster presented at The American Academy of Pain Medicine Annual Meeting, Phoenix, AZ, March 2014.

Horn JR, Hansten PD, Chan LN: Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007; 41: 674-680.

Gudin J: Opioid therapies and cytochrome P450 interactions. J Pain Symptom Manage. 2012; 44: S4-S14.

Smith HS: Opioid metabolism. Mayo Clin Proc. 2009; 84: 613-624.

Pergolizzi JV, Ma L, Foster DR, et al.: The prevalence of opioid-related major potential drug-drug interactions and their impact on health care costs in chronic pain patients. J Manag Care Pharm. 2014; 20: 467-476.



  • There are currently no refbacks.