Common Medications that Interact with Opioids 

Drug interactions are a leading cause of morbidity and mortality worldwide [2]. Polypharmacy, or the simultaneous use of more than one drug, is a common phenomenon in medicine. Whether a patient has multiple diagnoses or one diagnosis, it is often likely they will be taking more than one medication. An important role of the physician when prescribing any medication is to ensure there is no drug-drug interaction with other drugs a patient may be taking. This helps to avoid adverse reactions and prevent detrimental clinical consequences. Opioids are frequently used to manage pain during and after surgery, but drug interactions can be particularly negative, and there are a number of common medications that can interact with opioids or heighten stress on the body. 

Opioid analgesics can interact with other drugs through various mechanisms. Like many drugs, opioid elimination in the body largely relies on metabolism by the liver. Thus, the primary mechanism of opioid-drug interactions involves the liver through effects on enzyme metabolism, drug transporters, or the absorption of drugs [3]. Another mechanism is a pharmacodynamic interaction that can occur when two drugs combine in a synergistic or additive way to increase drug effects and toxicity levels. They can also have an oppositional effect where the drug’s effect is muted or the drug is metabolized quicker.  

When thinking about common medications that can interact with opioids, it is important to think in terms of which medications have a strong effect on the liver and liver metabolism. Antibiotics such as clarithromycin, telithromycin, ketoconazole, and antivirals such as atazanavir or indinavir are strong liver enzyme inhibitors [1,3]. Erythromycin, fluconazole, diltiazem, verapamil and even grapefruit juice are moderate liver enzyme inhibitors. With metabolism inhibited, opioids are more widely available in the body and the drug effect is stronger and acts longer in duration. This can be very dangerous and high doses can lead to overdose and sedation. 

Cimetidine, a commonly used antiacid for heartburn, stomach ulcers, and reflux, is a weak inhibitor but can nonetheless increase the duration of action of opioids [1]. As a provider, this is important to keep in mind as even prescribing an antiacid can affect a patient’s opioid dosing. More severely, the use of two sedating analgesics together such as opioids and benzodiazepines, like alprazolam, can cause death due to over-sedation of the central nervous system leading to diminished breathing [4]. Other groups of medications for which to be wary of concomitant use with opioids include antihistamines, anti-seizure medications, stimulants such as those used for ADHD, anti-anxiolytics, antidepressants, and antipsychotics [3].  

In summary, physicians must be cautious of existing medications and comorbidities when prescribing opioids, due to the potential for opioids to interact with many common drugs. For patients who have HIV and are taking antiretroviral (ARV) medication, extra caution should be used. Further, for patients with chronic pain who are on long-acting opioids such as methadone and buprenorphine, administering medications that could induce opioid metabolism by the liver can precipitate withdrawal symptoms [3]. Involving pharmacists and those who have a good understanding of drug-drug interactions is important when caring for patients with polypharmaceutical use, and especially when opioid medications are prescribed.  

References 

1. Maurer, Philip M., and Richard R. Bartkowski. “Drug Interactions of Clinical Significance with Opioid Analgesics.” Drug Safety, vol. 8, no. 1, Jan. 1993, pp. 30–48, 10.2165/00002018-199308010-00005. 

2. Lepakhin VK. Safety of medicines: a guide to detecting and reporting adverse drug reactions. World Health Organization Web site. 2002 Available at: http://whqlibdoc.who.int/hq/2002/WHO_EDM_QSM_2002.2.pdf 

3. McCance-Katz, Elinore F., et al. “Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and Other Frequently Prescribed Medications: A Review.” American Journal on Addictions, vol. 19, no. 1, Jan. 2010, pp. 4–16, 10.1111/j.1521-0391.2009.00005.x. 

4. Obadia, Yolande, et al. “Injecting Misuse of Buprenorphine among French Drug Users.” Addiction, vol. 96, no. 2, Feb. 2001, pp. 267–272, 10.1046/j.1360-0443.2001.96226710.x.