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Pharmacy Services | Therapeutic Notes
Benzodiazepines and opioids: A combination to avoid
   Opioid analgesics and benzodiazepines are two very commonly prescribed classes of medications within the United States. Opioid analgesics, such as morphine, hydromorphone, hydrocodone, codeine, and oxycodone, are often used for relief of pain and cough. Benzodiazepines, such as alprazolam, lorazepam, and diazepam, are frequently used for anxiety, insomnia, and seizures. The number of prescriptions issued for opioid medications has approximately tripled in the last fifteen years and overdoses and deaths from opioids have increased as well. Significant side effects of opioid medications include drowsiness, dizziness, constipation, and respiratory depression which can be life- threatening. Benzodiazepines also have side effects that include drowsiness and respiratory depression, therefore patients who take both classes of medications concomitantly are at an increased risk of respiratory depression, overdoses, and emergency room visits. In 2004, the number of emergency room visits associated with opioid and benzodiazepine use was 11 per 100,000 visits and increased to 34.2 per 100,000 visits by 2011. About 30% of overdoses from opioid medications occur in patients also taking benzodiazepines. It has been estimated that avoiding concomitant use of both benzodiazepines and opioids could decrease the risk of opioid overdoses that require medical attention by 15%.
Unfortunately, rates of prescribing opioids and benzodiazepines together have increased over the last several years. A recent study assessing more than 300,000 privately insured patients noted that there was an 80% relative increase in patients who were prescribed both benzodiazepines and opioids, either intermittently or chronically, from 2001 to 2013. Another study analyzing over 400,000 veterans, who had received opioids and healthcare from the Veterans Health Administration (VHA), discovered that 27% of these patients were also prescribed benzodiazepines simultaneously. These studies found that when patients use both opioids and benzodiazepines there is an increased risk of overdose and death.
The U.S. Food and Drug Administration (FDA) released a statement in August 2016 warning against the use of both of these classes of medications. Additionally, manufacturers were required to make adjustments to drug labeling information in order to help increase awareness of potentially dangerous effects of using these classes of medications. However, if patients are taking buprenorphine or methadone for medical management of opioid addiction, the FDA does recommend that they continue these agents even if they are taking benzodiazepines. It was recognized that discontinuing medication- assisted treatment for opioid addiction could lead to relapse with opioid use and present other dangers to the patient. The FDA still recommends that health care providers educate patients on possible risks of using these agents with benzodiazepines and attempt to minimize the amount of time that treatment overlaps with both of these agents if possible.
Educational efforts targeted to prescribers and patients can help decrease prescribing and use of these medications together. This has been illustrated by initiatives such as the VHA Opioid Safety Initiative which audited opioid prescriptions and then gave prescribers feedback based on these prescriptions and how they compared to national trends. This ultimately led to a 10% decrease in the number of patients who received opioid prescriptions and a 21% reduction in those that received opioids and benzodiazepines together. The availability of Narcan (naloxone) within the community without a patient specific prescription is another initiative that can help reduce death from overdoses with opioids. Naloxone is an opioid antagonist and has the strongest attachment to opioid receptors, so when administered it will remove opioid medications from these receptors and reverse the opioid medication’s effects. It is available for administration as an injection and as a nasal spray. In Delaware and many other states, naloxone injection has been available and the nasal spray has more recently become available to purchase directly from an outpatient pharmacy without a patient-specific prescription. C O N T I N U E D
Rachel Lynch, PharmD
Key Takeaways:
1. Use of opioid medications with benzodiazepines can lead to increased risk of dangerous side effects including respiratory depression and death and is attributed to approximately 30% of opioid overdoses.
3.Naloxone nasal spray can be used to reverse opioid overdose and is now available for purchase directly from a community pharmacist without a patient- specific prescription.
Rates of prescribing these medications together has increased; warranting FDA action and ongoing intervention to curb the prescribing and use of opioids and benzodiazepines.

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