ProDUR Update: Additive Toxicity Alert Now Focused Only On CNS Depressants

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Learning Objectives:

  • Describe the drug safety communications by the U.S. Food and Drug Administration (FDA) regarding the combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS).
  • Review the changes to the additive toxicity (AT) prospective drug utilization review (DUR) alert.
  • Summarize best practices for responsible prescribing of opioid medicines with benzodiazepines or other CNS depressants.

Key Points:

  • On August 31, 2016, the FDA announced that it will require Boxed Warnings added to the drug labeling of prescription opioid pain and cough medications and benzodiazepines due to serious side effects, including slowed or difficult breathing and deaths.
  • Effective June 1, 2018, the Medi-Cal fee-for-service prospective DUR system has been updated to generate an AT alert when a patient reaches a threshold of four active prescriptions within the following therapeutic categories: opioid pain or cough medications, benzodiazepines, skeletal muscle relaxants, other sleep drugs and tranquilizers (non-benzodiazepine), antipsychotic medications, and other selected psychotropic medications with CNS depressant properties. Previously, the AT alert had included all psychotropic and controlled (scheduled) drugs.
  • With the AT alert updated to focus exclusively on CNS polypharmacy, a review of the June 2018 AT alert data found a 17% decrease in AT alerts, when compared to June 2017. This indicates the updated AT alert has already been beneficial.
  • Among the 1,964 beneficiaries that generated an AT alert in June 2018, the vast majority (n = 1,871; 95%) were enrolled in the Medi-Cal fee-for-service program and were under 65 years of age (n = 1,935; 98%), primarily due to the majority of drugs included in the AT alert being covered through Medicare or Managed Care Plans (MCPs). Many of these beneficiaries had additional risk factors for serious adverse events, including co-morbid mental health conditions (n = 1,248; 64%), suicide attempts and/or ideation (n = 174; 9%), and alcohol and/or substance abuse (n = 158; 8%). A total of 307 beneficiaries (16%) had both a paid claim for an opioid medication and a paid claim for a benzodiazepine.
  • If CNS polypharmacy cannot be avoided, health care professionals should work to limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect.
  • Health care professionals should take additional actions and precautions when buprenorphine or methadone is used in combination with benzodiazepines or other CNS depressants, including developing a treatment plan and educating patients about the serious risks of combined use, including overdose and death, that can occur with CNS depressants even when used as prescribed, as well as when used illicitly.

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Posted on July 31st, 2018 and last modified on September 9th, 2022.