Meperidine was synthetically derived in 1939 as an anticholinergic agent, but was discovered to possess analgesic properties shortly after. Although it’s a weak agonist at the mu opioid receptor, anecdotal evidence suggested it was a good alternative to morphine because it circumvented morphine’s most common adverse effects, specifically respiratory depression and chemical dependency. However, clinical experience has taught us differently. 
 
A quick search of the current literature revealed the fostered benefits of meperidine, including inducing less spasm on the sphincter of Oddi and the biliary tract, were simply false. Meperidine has never been studied in specific populations through randomized, controlled trials, so its purported benefits over other opioids have fallen short. 
 
As a matter of fact, meperidine brings a set of various disadvantages, including short duration of action (half-life ~2-3 hours) and subpar analgesic effects. At common doses (25-50 mg every 4-6 hours), serum levels were found to be suboptimal, making it a poor choice for acute or chronic pain. 
 
Morphine is the gold standard therapy in acute pain management, with hydromorphone being the second alternative. Equianalgesic doses of 10 mg of morphine equals 75 mg of meperidine and 1.5 mg of hydromorphone. Through a simple cross-multiply calculation, you can see 25-50 mg of meperidine equal 3-6 mg of morphine. Nevertheless, when we take opioid potency and the 24-hour total dose into account to calculate equivalencies, it’s clear meperidine won’t be the best choice for pain control.
 
Meperidine’s metabolism brings an additional set of challenges. It’s metabolized by 2 distinctive pathways, but the most clinically significant one occurs through the cytochrome P450 system that produces the nonopioid active metabolite, normeperidine. Normeperidine acts as a very weak analgesic and is also a neurotoxin that increases the risk of seizures, delirium, and restlessness, among other adverse effects.
 
Normeperidine’s main route of elimination is renal, and in normal patients, its half-life is very long (14-21 hours). On the other hand, the half-life of this metabolite can extend up to 35 hours in patients with acute or chronic renal failure, meaning a normal patient will reach significant accumulation of the metabolite way before the parent drug reaches steady state. Imagine how this can turn out in a chronic kidney disease patient.
 
Additionally, the opioid antagonist naloxone has no effect on normeperidine’s actions in the central nervous system. Moreover, meperidine has serotonergic and noradrenergic properties, so one concern that can’t be dismissed is the potential to induce serotonin syndrome in patients who take antidepressants like selective serotonin reuptake inhibitors and monoamine oxidase inhibitors. 
 
According to the Agency for Healthcare Research and Quality, Institute of Safe Medication Practices, and Joint Commission, meperidine should be reserved for only brief use (<48 hours) in moderate to severe pain in patients with normal renal function. Other short-term indications include preprocedural analgesia, postanesthesia shivering, and blood product-induced rigors. Many health systems have achieved control through meperidine use, including the Veterans Affairs Administration.
 
Overall, appropriate pain management is often overlooked by many institutions across the United States and its territories. For example, there are still many hospitals in Puerto Rico where meperidine is a first-line analgesic in the emergency department. Research also shows the elderly population has longer lengths of stay and constitutes the majority of hospital admissions, and with that comes more complicated medication regimens. Furthermore, the Beers Criteria lists meperidine as an inappropriate medication for individuals older than 65 years. Thus, meperidine use should be discouraged in this population. 
 
One of the cornerstones of pain management is being knowledgeable of dose equivalencies, but pharmacists should also strive to offer the safest alternatives for our aging population. Thorough evaluation of past medical history and current medication therapy is key to assess the risk-benefit ratio for choosing the best opioid.
 
Reducing meperidine use can be a challenging task, but it must be given the priority it needs. Our most vulnerable patients depend on us to help them avoid this drug’s serious adverse effects.