Case Report & Results
A 67-year-old Caucasian female presented with a past medical history of chronic, intractable lower back pain, hypertension, anxiety, and heart failure. Her physician prescribed several medications to manage her various conditions, including oxycodone tablets, 15mg four times daily; duloxetine capsules, 60mg once daily; lorazepam tablets, 1mg twice daily as needed; metoprolol succinate tablets, 50mg once daily; and lisinopril tablets, 10mg once daily. At a follow-up appointment with her physician, she reported experiencing on going uncontrolled pain. Following multiple increases in her oxycodone dosage, from a total daily dose of 20mg to 60mg, she continued to experience inadequate pain control. When her physician sought assistance, the clinical pharmacist suggested that PGx testing would be helpful to assess appropriateness of opioid therapy and guide medication changes. The physician then ordered a PGx test.
A DNA sample was collected by buccal swab and analyzed by a genetics laboratory. The results were then interpreted by the clinical pharmacist. The patient was identified as an intermediate metabolizer (IM) for the cytochrome P450 2D6 (CYP2D6) drug-metabolizing enzyme, with a *9|*40 genotype (Table 1).
Considering the patient’s previous unsuccessful trials of non-opioid treatments (e.g., nonsteroidal anti-inflammatory drugs, skeletal muscle relaxants), the clinical pharmacist recommended that the physician consider an alternative opioid such as oxymorphone, hydromorphone, or morphine, which are not metabolized by the CYP2D6 drug-metabolizing enzyme. After her physician changed the opioid from oxycodone to hydromorphone 2mg four to six times per day as needed, the patient’s pain control improved significantly.
Importantly, the dose of hydromorphone was established as if the patient was opioid naïve, since metabolic transformation of oxycodone into oxymorphone was impaired due to genetic polymorphisms, drug-drug interactions and drug-drug-gene interactions. A direct dose calculation using morphine milligram equivalent dose algorithms was not applied, considering that the dose of oxycodone was increased up to 60mg per day.