What are the risks of concurrent use of opioids and clonazepam (benzodiazepine)?

From the Guidelines

The concurrent use of opioids and clonazepam should be avoided whenever possible due to the significant risk of respiratory depression, excessive sedation, and potentially fatal overdose. This combination of medications can have devastating consequences, including difficulty breathing, extreme drowsiness, confusion, impaired coordination, and the possibility of falling into a coma 1. The effects of these medications multiply rather than simply add together, making this drug interaction responsible for many preventable deaths each year.

Key Risks and Considerations

• Respiratory depression: The combination of opioids and clonazepam can lead to decreased respiratory drive, increasing the risk of respiratory failure 1.
• Excessive sedation: Patients taking both medications may experience extreme drowsiness, impaired coordination, and confusion, increasing the risk of accidents and injuries 1.
• Potentially fatal overdose: The concurrent use of opioids and clonazepam can increase the risk of overdose, which can be fatal if not recognized and treated promptly 1.

Patient Education and Management

• Patients should be educated about the serious risks associated with taking opioids and clonazepam together and advised to never adjust doses on their own 1.
• Patients should be cautioned to avoid alcohol completely while on these medications, as it can exacerbate the risks 1.
• Patients and their family members should be taught to recognize overdose signs, such as very slow or irregular breathing, blue-tinged lips, and inability to wake up, and to call 911 immediately if these occur 1.
• Clinicians should carefully weigh the benefits against the serious risks and consider alternative treatment options before prescribing both medications concurrently 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. Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for use in patients for whom alternative treatment options are inadequate Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone If a decision is made to prescribe clonazepam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation Advise both patients and caregivers about the risks of respiratory depression and sedation when clonazepam is used with opioids

The risks of concurrent use of opioids and clonazepam include:

• Profound sedation
• Respiratory depression
• Coma
• Death It is recommended to:
• Reserve concomitant prescribing for patients with no alternative treatment options
• Use the lowest effective dosages and minimum durations of concomitant use
• Closely monitor patients for signs and symptoms of respiratory depression and sedation 2

From the Research

Risks of Concurrent Use of Opioids and Clonazepam (Benzodiazepine)

The concurrent use of opioids and clonazepam (benzodiazepine) poses significant risks to patients, including:

• Increased risk of potentially lethal respiratory depression 3
• Higher risk of mortality and severe adverse respiratory events 3
• Increased risk of overdose or serious opioid-induced respiratory depression, particularly in patients receiving ongoing opioid therapy 4
• Risk of severe respiratory depression, especially when opioids are used in combination with other central nervous system depressants, such as benzodiazepines 5, 6

Mechanisms of Risk

The mechanisms underlying these risks include:

• Pharmacodynamic interactions between opioids and benzodiazepines, which can result in additive or synergistic effects on respiratory depression 6
• Pharmacokinetic interactions between opioids and benzodiazepines, which can affect the metabolism and clearance of these drugs 6
• Decreased sensitivity of peripheral chemoreceptors to carbon dioxide and decreased activity in the central respiratory centers, leading to respiratory depression 5

Clinical Implications

The concurrent use of opioids and clonazepam (benzodiazepine) requires careful consideration of the potential risks and benefits, particularly in patients with a history of substance abuse or those receiving high doses of these medications. Clinicians should be aware of the potential for respiratory depression and take steps to mitigate this risk, such as:

• Monitoring patients closely for signs of respiratory depression 3, 4
• Using naloxone or other opioid antagonists to reverse opioid-induced respiratory depression, although this may not be effective in cases of buprenorphine-induced respiratory depression 4, 6
• Considering alternative treatments or adjusting the doses of opioids and benzodiazepines to minimize the risk of respiratory depression 3, 4