What are the concerns of a patient remaining on opioid medication and clonazepam (Klonopin)?

From the Guidelines

Patients taking opioid medication and clonazepam (Klonopin) concurrently should be closely monitored due to the high risk of respiratory depression, overdose, and death, and clinicians should avoid prescribing these medications together whenever possible. The primary concern with this combination is the dangerous risk of respiratory depression, as both medications suppress the central nervous system, which can lead to slowed or stopped breathing, potentially resulting in overdose and death 1. This risk is significantly amplified when these medications are taken together. According to the CDC guideline for prescribing opioids for chronic pain, clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible, with a recommendation category of A and evidence type of 3 1.

Some of the key concerns with this combination include:

• Respirborne depression and overdose risk
• Physical dependence and tolerance, requiring increasing doses over time to achieve the same effect, which further increases overdose risk
• Cognitive impairment, including memory problems, confusion, and impaired judgment
• Paradoxical effects where anxiety or pain actually worsens rather than improves with long-term use
• Severe and potentially life-threatening withdrawal symptoms if either medication is stopped abruptly

Given these risks, it is crucial to regularly reassess the risk-benefit ratio, consider alternative treatments, and have a clear tapering plan in place when appropriate. Clinicians should also check the prescription drug monitoring program (PDMP) for concurrent controlled medications prescribed by other clinicians and consider involving pharmacists and pain specialists as part of the management team when opioids are co-prescribed with other central nervous system depressants 1. If tapering is necessary, it may be safer and more practical to taper opioids first, and benzodiazepines should be tapered gradually to avoid abrupt withdrawal symptoms 1.

From the FDA Drug Label

Warnings Risks from Concomitant Use with Opioids: Concomitant use of benzodiazepines, including clonazepam, and opioids may result in profound sedation, respiratory depression, coma, and death. The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites, and opioids interact primarily at mu receptors When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation

The concerns of a patient remaining on opioid medication and clonazepam (Klonopin) include:

• Respiratory depression: The combination of opioids and benzodiazepines can increase the risk of respiratory depression, which can be life-threatening.
• Sedation: The concomitant use of opioids and benzodiazepines can cause profound sedation, which can impair cognitive and motor function.
• Coma and death: The combination of opioids and benzodiazepines can increase the risk of coma and death.
• Abuse, misuse, and addiction: The use of benzodiazepines, including clonazepam, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose and death.
• Dependence and withdrawal reactions: The continued use of clonazepam may lead to clinically significant physical dependence, and abrupt discontinuation or rapid dosage reduction can precipitate acute withdrawal reactions, which can be life-threatening. It is recommended to limit dosage and duration of concomitant use of benzodiazepines and opioids, and to follow patients closely for signs and symptoms of respiratory depression and sedation 2.

From the Research

Concerns of Long-Term Opioid and Clonazepam Use

• The concurrent use of opioids and benzodiazepines, such as clonazepam, poses a significant challenge for clinicians managing chronic pain due to the increased risk of fatal or nonfatal overdose and aberrant behaviors 3.
• Patients on chronic opioid therapy with benzodiazepines are at a higher risk for adverse events, overdose, and death, necessitating close monitoring and consideration of treatment adjustments 3, 4.
• The combined use of opioids and benzodiazepines increases the risk of potentially lethal respiratory depression, emphasizing the need for careful management and monitoring 4.
• Long-term opioid use can lead to opioid-induced tolerance and hyperalgesia, requiring increased doses to achieve the same effect and potentially exacerbating pain sensation rather than relieving it 5, 6.
• The development of tolerance and hyperalgesia can be addressed through various strategies, including tailored treatment, interventional techniques, and reducing opioid consumption 6.

Risks and Monitoring

• Ongoing screening for aberrant behavior, monitoring of treatment compliance, and documentation of medical necessity are essential for patients on chronic opioid therapy with benzodiazepines 3.
• Urine drug testing is a crucial tool for therapeutic drug monitoring, helping to ensure patient safety and adherence to the treatment plan 3.
• The risk of harm and benefit of combining opioids and benzodiazepines strongly correlates with the context, and benefits may outweigh the risks in certain situations, such as in hospice settings 4.