Clonazepam with Difenoxin Interaction Details
Brand Names Associated with Clonazepam
- Clonazepam
- Klonopin®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 12, 2023
Interaction Effect
Increased risk of respiratory and CNS depression
Interaction Summary
Concomitant use of benzodiazepines, including clonazepam, and opioids may result in profound sedation, respiratory depression, coma, and death. Observational studies demonstrated coadministration of opioids and benzodiazepines increases the risk of drug-related mortality compared to opioids alone. Reserve concomitant use for patients for whom alterative treatment options are inadequate. Limit dosages and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation, and consider prescribing naloxone for the emergency treatment of opioid overdose . Cessation of benzodiazepines is preferred over concomitant use with the opioid class. Monitoring in a higher level of care or taper may be appropriate; gradually tapering a patient off a prescribed benzodiazepine or decreasing to the lowest effective dose may also be appropriate. Consider using alternative options for the treatment of anxiety or insomnia .
Severity
Major
Onset
Unspecified
Evidence
Theoretical
How To Manage Interaction
Concomitant use of benzodiazepines, including clonazepam, and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alterative treatment options are inadequate. Limit dosages and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose . Cessation of benzodiazepines is preferred over concomitant use with the opioid class. In some cases, monitoring in a higher level of care or taper may be appropriate. In others, gradually tapering a patient off a prescribed benzodiazepine or decreasing to the lowest effective dose may be appropriate. Consider using alternative options for the treatment of anxiety or insomnia .
Mechanism Of Interaction
Additive CNS depression
Literature Reports
A) The rate of emergency department visits involving non-medical use of concomitant benzodiazepines and opioid analgesics increased significantly over the period from 2004 to 2011, from 11 visits per 100,000 population to 34.2 visits per 100,000 population. Also, deaths from drug overdose involving concomitant benzodiazepines and opioid analgesics (including both prescribed doses and doses greater than prescribed) increased from 0.6 per 100,000 population to 1.7 per 100,000 population. The proportion of opioid overdose deaths for which benzodiazepines were also implicated increased from 18% to 31% .
B) In a prospective cohort study performed in North Carolina, overdose deaths in patients who were dispensed both opioids and benzodiazepines were 10-fold greater than those dispensed opioids alone (7 per 10,000 person-years vs 0.7 per 10,000 person-years). A case-cohort study in the Veterans Health Administration demonstrated that patients taking opioids with a benzodiazepine prescription history or current benzodiazepine prescriptions had an increased risk of death due to overdose compared with patients taking opioids without a history of benzodiazepine prescription, risk increased 2.33- to 3.86-fold in patient with current or historical prescriptions for benzodiazepines. As daily benzodiazepine doses increased, risk of death due to drug overdose increased as well .
C) Observational studies demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone .
Clonazepam Overview
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Clonazepam is used alone or in combination with other medications to control certain types of seizures. It is also used to relieve panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Clonazepam is in a class of medications called benzodiazepines. It works by decreasing abnormal electrical activity in the brain.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.