Oxycodone and CYP2D6

Joseph Marchiano, Pharm.D. Candidate; Emily Loudermilk, Pharm.D. Candidate; Katherine Albright, Ph

 

About the Drug

Oxycodone (Oxycontin®, found in Percocet®) is prescribed in order to treat moderate to severe pain. Oxycodone may be used to treat pain from cancer, various surgeries, and birth procedures in addition to conditions such as restless leg and Tourette’s syndromes. Oxycodone has a high potential for addiction, and it is classified as schedule II narcotic in the U.S. It is very important to follow your doctor’s instructions about when to take this medicine.

Drugs like oxycodone are called opioids. These medications are grouped together because they all resemble morphine and help to treat pain. In order to work, oxycodone needs to activate very specific receptors in the brain or gut known as µ (pronounced “mew”) receptors. This starts a chain reaction in the body that decreases the amount of pain felt and slows down your intestines which may cause constipation. Euphoria, respiratory depression, and even physical dependence may result from taking this medication.

About the Gene

A gene known as CYP2D6 (pronounced “sip-two- dee-six”) plays a large role in controlling how much oxycodone gets into your body after taking a pill. This gene is found in the liver, and it makes a protein called “cytochrome P450 2D6.” This protein helps to process many different kinds of drugs that the body may encounter.

About the Drug-Gene Interaction

The protein made by CYP2D6 processes oxycodone into different forms. One of the main products of this reaction is morphine. This reaction must occur for oxycodone to work effectively. This means that your body uses CYP2D6 to turn oxycodone into morphine which then helps to control pain. Therefore, if the CYP2D6 gene does not work properly, then it may be necessary to modify treatment.

Patients that are poor metabolizers or intermediate metabolizers will not process oxycodone into morphine quickly enough. This means that the drug may not work that well for them, and they are recommended to have their prescriber consider an alternate medication. Ultra-rapid metabolizers process the drug too quickly, and they should also talk to their doctor about using a different medicine.

Drug-Gene Interaction Example

A 55-year old Caucasian male, Jay, presented to the hospital with osteoarthritic knee pain. Following a torn ACL incident in his youth, Jay had frequently exhibited knee pain but failed to respond to non- surgical treatment. It was decided that the patient should receive a full knee replacement. In order to control the post-operative pain it was also decided to start an opioid medication. Before the surgery he elected NOT to have the function of his CYP2D6 analyzed. Jay was given IV ketorolac every eight hours and oxycodone twice a day orally. He was also given hydrocodone every 4 hours as needed for breakthrough pain.

After about 3 days post-op, he complained that his pain medication regimen wasn't adequately controlling his pain. The patient’s pain medication regimen was increased. After 4 days post-op, he complained that the oxycodone was causing some GI upset and still had no pain alleviation. He was then switched to an IV fentanyl infusion, which was reported to control pain very well. Genotype testing was done on the patient and results showed that his CYP2D6 gene could not process oxycodone into morphine.

CYP2D6 testing does not completely rule out the risks of taking oxycodone, nor does it guarantee that the medication will work for you. Genetic testing is a guide to personalize the treatment of patients, maximize benefit, and minimize harm.

Provider Information

The links below provide access to important articles and information relative to oxycodone. The links are to external websites and will be checked regularly for consistency.

Sources of Information

Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. 2015. Oxycodone; [2013 Sept 6; cited 2015 Jan 20]; [2 screens]. Available from: http://www.clinicalpharmacology- p.com/Forms/Monograph/monograph.aspx?cpnum=457&sec=monphar&t=0/.

DailyMed [Internet]. Bethesda (MD): U.S. National Library of Medicine; c1993-2015. Oxycodone Hydrochloride; [cited 2015 Nov 23]; [about 3 screens]. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=094b64b3-cd32- 4de5-afb6- ea00d9caad74/.

Samer C, Daali Y, Wagner M, et al. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety. Br J Pharmacol. 2010;160(4):919-930.

Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB and Klein TE. Pharmacogenomics knowledge for personalized medicine. Clin Pharmcol Ther. 2012;92(4):414-417.