CMS Issues Education Regarding Concurrent Use of Opioids and Benzodiazepines

CMS, Medicare Set-Aside Blog, Opioids, Rx/Pharmacy on September 24, 2019
Posted by Leah King, PharmD, JD, Independent Pharmacy Consultant

On July 1st, CMS issued a Medicare Learning Network (MLN) article regarding the potential dangers associated with the concurrent use of opioids and benzodiazepines. This combination of drugs has always been prescribed cautiously in light of the depressive effect that both drugs can have on a patient’s ability to breathe. When used together, the resulting respiratory depression can be life threatening and possibly fatal. Additionally, the simultaneous use of both drugs can cause an increase in sedation as a side effect. Both opioids and benzodiazepines independently have the potential for addiction. Opioids are generally classified as schedule II controlled substances, which represents the highest rating for addiction potential. Benzodiazepines are generally classified as schedule III controlled substances, which represents a lower level of addiction potential relative to schedule II but nonetheless poses significant risk. 

Since as early as the 1970’s, a concerning trend emerged regarding the use of opioids and benzodiazepines as one that was more likely to result in overdose and the need for emergency medical treatment. Benzodiazepines have been noted to enhance the effect of opioids and unfortunately in some cases, patients intentionally mix these drugs to produce a greater feeling of euphoria.

It is estimated that more than 30% of opioid overdoses involve the use of benzodiazepines.[1] Between 1996 and 2013, there was a 67% increase in benzodiazepine prescriptions filled, from 8.1 million to 13.5 million.[2] 

In August of 2016, the FDA issued a black box labeling requirement for manufacturers of opioids and benzodiazepines. A black box warning, which is quite literally a warning that appears in bold text within a box near the top of the drug’s label, is the strongest warning that the FDA can require. In this case, the FDA required manufacturers to detail that the drugs can be fatal when used together.

More recently, CMS published more specific guidelines on how to avoid the use of this combination via the MLN publication. The article advises of potential negative consequences that result from the concurrent use of benzodiazepines and opioids, such as:

  • Higher risk of overdose deaths
  • Higher risk of suicide
  • Worse treatment outcomes; and
  • Increased health service use

The MLN publication discusses five principles for prescribers to consider when utilizing opioids and benzodiazepines. Many of the principles are focused on reducing and/or eliminating the use of one or both drugs. The principles are:

  1. Avoid the initial combination by offering alternative approaches. CMS warns against the use of benzodiazepines as a treatment for chronic pain, citing a lack of efficacy. The MLN publication features a table which lists several alternatives to both benzodiazepines and opioids. Alternatives to benzodiazepines include psychotherapy, relaxation techniques, alternative drug categories and others. Alternatives to opioids include topical medications, trigger point injections, a TENS unit and others. For additional alternatives, please refer to the full publication, which can be found here:
  2. If new prescriptions are needed, limit the dose and duration.  CMS recommends therapy of seven days or fewer but no more than two weeks. When using opioids and benzodiazepines in combination, even for a short duration, patients must be educated about the warning signs of adverse reactions. Prescribers need to have clear expectations regarding the benefit of treatment and a plan to taper and/or discontinue therapy when appropriate.
  3. Taper long-standing medications gradually and, when possible, discontinue. CMS cautions against abrupt discontinuation of benzodiazepines for patients who have been long-term users, due to the risks of severe withdrawal, increase in suicidal thoughts, sleep disturbances and symptom recurrence. One method of benzodiazepine taper discussed in the MLN publication is to convert patients to a long-acting benzodiazepine and reduce the total daily dose by 10 to 25 percent every one to two weeks. The process of tapering a benzodiazepine requires patient buy-in and generally occurs very slowly over the course of months or even years. In order to taper opioid medications, CMS suggests utilizing the recommendations previously published by the Centers for Disease Control. Those recommendations can be accessed via this link:
  4. Continue long-term co-prescribing only when necessary and monitor closely. The continued use of opioids and benzodiazepines involves a risk-benefit analysis on the part of the prescriber, based on the patient’s unique clinical circumstances. In patients where long-term use of both medications is deemed to be clinically appropriate, prescribers should be sure to discuss with patients the risks and benefits of continued use. One potential risk is the development of tolerance to one or both medications, which can lead to the need for higher doses in order to maintain the same therapeutic effect. Adherence monitoring is a way that prescribers can ensure medication compliance and guard against misuse of the drugs. Patients utilizing both medication classes on a long-term basis should be evaluated in the prescriber’s office at least every three to six months. More frequent monitoring may be necessary. 
  5. Provide rescue medication (for example, naloxone) to high-risk patients and their caregivers.  When prescribers deem naloxone to be appropriate, this should be discussed with patients and caregivers. Prescribers should ensure that patients and caregivers are able to recognize an overdose situation and know how to administer naloxone. Patients are often unable to self-administer naloxone and as a result, caregiver education is imperative. Many states permit pharmacists to dispense naloxone without a prescription, which helps to increase the availability of this potentially life-saving medication.

Here on our blog, we’ve discussed the many methods our federal government has undertaken to help reverse the problematic opioid trend. We are hopeful that the MLN publication will serve as a resource in educating prescribers about ways to avoid the potentially deadly combination of opioid and benzodiazepine drug therapies.

It is important to note, that the concurrent use of opioids and benzodiazepines can occur in workers’ compensation cases and as a result, this represents a unique drug utilization assessment opportunity for the carrier. MEDVAL is uniquely positioned to help facilitate cost-savings associated with optimizing drug therapy. If you would like to discuss a potential drug utilization assessment as it relates to opioids, benzodiazepines, or other medications, please contact us at

[1] NIH National Institute on Drug Abuse: Benzodiazepines and Opioids. Updated March 2018.

[2] Ibid.