Drug Safety Alerts

Opioid Medicines with Benzodiazepines MedWatch

08/31/2016

On August 31, 2016, the United States Food and Drug Administration (FDA) issued a MedWatch to announce that a review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths.  Opioids are used to treat pain and cough; benzodiazepines are used to treat anxiety, insomnia, and seizures. In an effort to decrease the use of opioids and benzodiazepines, or opioids and other CNS depressants, together, the FDA is adding Boxed Warnings to the drug labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines.

A list of all approved prescription opioid pain and cough medicines, and benzodiazepines and other CNS depressants is provided here:

The FDA conducted and reviewed several studies showing that serious risks are associated with the combined use of opioids and benzodiazepines, other drugs that depress the CNS, or alcohol. Based on these data, the FDA is requiring several changes to reflect these risks in the opioid and benzodiazepine labeling, and new or revised patient Medication Guides. These changes include the new Boxed Warnings and revisions to the Warnings and Precautions, Drug Interactions, and Patient Counseling Information sections of the labeling.

The FDA is continuing to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy (MAT) drugs used to treat opioid addiction and dependence. The FDA is also evaluating whether labeling changes are needed for other CNS depressants, and will update the public when more information is available. 

The FDA recommends that health care providers should limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate.  If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect.  Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms.  Avoid prescribing prescription opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol.

The FDA has provided the following information for health care providers:

• Concomitant use of opioid pain or cough medicines and benzodiazepines, other central nervous system (CNS) depressants, or alcohol may result in profound sedation, respiratory depression, coma, and/or death.

• Reserve concomitant prescribing of opioid analgesics with benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.

• Avoid use of prescription opioid cough medications in patients on benzodiazepines or other CNS depressants.

• If the decision is made to concomitantly prescribe a benzodiazepine or other CNS depressant for an indication other than epilepsy with an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.

• If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid, and titrate based on clinical response.

• Monitor patients closely for respiratory depression and sedation.

• Advise both patients and caregivers about the risks of respiratory depression and sedation if opioids are used with benzodiazepines, alcohol, or other CNS depressants (including illicit or recreational drugs).

• Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the opioid and benzodiazepine or other CNS depressant have been determined.

• Screen patients for risk of substance-use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants, including alcohol and illicit or recreational drugs.

• Encourage patients to read the Medication Guides or patient information leaflets that come with their filled prescription(s).

• Report adverse events involving opioids, benzodiazepines, or other medicines to the FDA.

CVS Caremark Response: There have been no recalls issued on this product by the manufacturers because of this action. CVS Caremark Mail Service Pharmacy will continue to dispense these products.

For more information about this issue, health care providers may contact the FDA consumer inquiry line at 1-888-INFO-FDA (1-888-463-6332) or visit www.fda.gov.