Economic Implications of Potential Drug–Drug Interactions in Chronic Pain Patients

Robert Taylor Jr; Joseph V Pergolizzi Jr; R Amy Puenpatom; Kent H Summers


Expert Rev Pharmacoeconomics Outcomes Res. 2013;13(6):725-734. 

In This Article


Clinicians must be increasingly mindful when prescribing CYP450-metabolized agents. In these studies, the CYP450-metabolized agents counted as index opioids were codeine, fentanyl, hydrocodone, methadone, oxycodone and tramadol. These are safe, effective and well-established opioid analgesic products, but they may not be appropriate for use in patients who are or may be taking other CYP450-metabolized agents. Thus, alternative opioid analgesic products such as hydromorphone, morphine and oxymorphone may be useful substitutes. The treatment of chronic pain patients requires prescribers to know and consider the prescriptions patients may receive from other physicians. This may involve actively soliciting the patient for information about all drugs and OTC products.

Other interventions may include the use of complementary alternative medicine (CAM) practices. Current trends indicate that CAM practices are increasing among adults, with approximately 38% of the US adult population utilizing these therapies.[48] Physicians should be aware of different therapies, which may be used as alternatives or in addition to opioid analgesics to manage chronic pain as well as to manage other comorbidities that may plague the chronic pain patient. For example, cancer pain patients have tried various nonpharmacologic approaches for pain relief including physical therapy, massages, hot and cold therapy and transcutaneous electrical nerve stimulation.[49] In a study analyzing 401 Veterans Administration patients with chronic noncancer pain, 20–56% tried either acupuncture, massage or chiropractic care to relieve pain prior to the study with >80% willing to try the therapies during the study.[50] Utilizing these, nondrug therapies can potentially reduce the number of prescriptions a patient is written and thus reduce the risk associated with polypharmacy and DDEs. It should be noted that some pharmacologic CAM therapies (e.g., St John's Wort or other herbal medicines) can be metabolized through CYP450 and may potentially contribute to DDEs if index opioids are consumed concomitantly.

To support the knowledge and awareness of physicians and pharmacists, electronic prescribing systems offer a unique advantage toward the fight to prevent DDEs and DDIs. Many pharmacy chains and hospital pharmacies are integrating computer systems into their prescribing routine.[51] Some systems include features beyond that of just identifying a DDI. These may include alerts related to issues such as drug–disease (78%), drug–age (67%) and inappropriate dosage (79%), as well as laboratory and pediatric dosing recommendations.[52] Though many pharmacies are incorporating such software, the ability to identify DDIs is not perfect. In one study analyzing 64 pharmacies with integrated DDI alert systems in the state of Arizona, only 28% of the pharmacies were able to identify interactions.[53] In addition, many of these systems do not incorporate over the counter CAM therapies, thus limiting these systems even further. However, these systems are not optimized and physicians and pharmacists should use them to supplement their own knowledge and not as a complete replacement. Patients should consider going to the same pharmacy/pharmacist and ones that have integrated, prescribing/dispensing information systems. Current clinical decision support software in pharmacies is supported by physicians and pharmacists, but improvements are still warranted to increase their clinical utility.[54] Other DDI alerting systems are currently being developed and tested, but their effectiveness has been documented to be minimal.[55] As the increase in our knowledge of DDIs occurs, databases should be updated accordingly.