Opioids

Clarissa Chan, PharmD

Chronic pain is common in the U.S. population and one of the main reasons patients seek medical care. Between 10% to 60% of adults 18 years and older report experiencing chronic pain or persistent pain lasting at least three to six months, according to a November 2021 study by Michaud and colleagues published in the Journal of Personalized Medicine.

According to the study, more than 65% of patients who take an opioid for chronic pain also take at least one other medication concomitantly, increasing the likelihood that patients will experience drug–drug interactions (DDIs).

Opioid-related drug interaction classifications

Mark Garofoli, PharmD, MBA, BCGP, CPE, a clinical assistant professor at WVU School of Pharmacy, said he usually classifies opioid interactions into these categories: metabolic (CYP-450/Transporters), QTc interval prolongation, serotonergic, sedatives, pharmacogenomics, gender, and age.

Opioids like codeine, hydrocodone, oxycodone, and tramadol are metabolized in the body by the cytochrome P450 (CYP) enzymatic system, specifically the CYP2D6 isoenzyme, to activate the prodrug (inactive substrate) resulting in pain relief from the active metabolites morphine, hydromorphone, oxymorphone, and O-desmethyl-tramadol, respectively.

Issues arise when other coadministered drugs interact to inhibit or have a greater affinity for the CYP2D6 isoenzyme, thereby interfering with the activation process of these opioids.

“When it comes to metabolic and pharmacogenomic opioid interactions, CYP2D6 and CYP3A4 are the main players,” said Garofoli, who was not involved with the study. He said therapy selection and dosage changes are most common in regard to CYP2D6 (e.g., tramadol and codeine).

Since these DDIs are associated with decreased concentrations of the active opioid metabolites, which results in inadequate analgesic effects, variable effectiveness, safety concerns, Michaud and colleagues conducted a retrospective, observational cohort analysis examining drug claims data to investigate the effects of opioid use and DDIs on health care costs.

They found that patients who took opioids with interacting drugs tended to be at higher risk for adverse drug events, higher overall yearly drug costs, and had a greater average daily intake of opioids than patients who took opioids with no interacting drugs.

To identify and evaluate opioid-related drug issues from pharmacogenomic data, the research team used a clinical decision support software from Tabula Rasa HealthCare called MedWise Science.

Sedative interactions

Patients taking opioids and other drugs with sedative properties like benzodiazepines risk respiratory depression, cognitive impairment, and even death from overdose.

“If you’re a licensed health care professional with a pulse, you obviously know of the major concern for opioid and benzodiazepine interactions.

“The question, however, is what you do about it for each and every patient,” said Garofoli.

CDC recommends clinicians avoid prescribing benzodiazepines concurrently with opioids whenever possible to prevent potential dangers.

Pharmacists should also recommend patients have naloxone on hand in case of accidental opioid overdose.

According to NIH, common signs of an opioid overdose include unconsciousness, very small pupils, slow or shallow breathing, vomiting, an inability to speak, faint heartbeat, limp arms and legs, pale skin, and purple lips and fingernails.

Serotonergic interactions

Many medications have serotonergic effects that can interact with serotonergic pain management opioids, such as methadone, meperidine, levorphanol, and tramadol, yet how pharmacists explain potential interactions to patients and colleagues goes a long way, said Garofoli.

Pharmacists should advise patients not to wait to contact their health care provider if they feel ill, he said. He advises pharmacists use a very direct, yet conversational manner to approach the topic.

“Approaching opioid interactions while striving for safe and effective pain management for patients is often like driving on a highway with one side stating that the right lane closes in 1 mile and another sign reading that the left lane closes in 2 miles; we’re often left wondering what lane, or what treatment option to utilize,” said Garofoli. ■