Addiction, Abuse, and Misuse; Life -Threatening Respiratory Depression;  Risk Evaluation And Mitigation Strategy (REMS); Neonatal Opioid Withdrawal Syndrome; Cytoshrome P450 3A4 interaction; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants; and Monoamine Oxidase (MOA) Inhibitors Interactions; Risk Evaluation and Strategy (REMS)

Addiction, Abuse, and Misuse

• Meperidine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing Meperidine, and monitor all patients regularly for the development of these behaviors and conditions.
• Patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose. 

Life-Threatening Respiratory Depression

• Serious, life-threatening, or fatal respiratory depression may occur with use of Meperidine. Monitor for respiratory depression, especially during initiation of Meperidine or following a dose increase.
• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

Neonatal Opioid Withdrawal Syndrome

• Prolonged use of Meperidine during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Cytochrome P450 3A4 Interaction

• The concomitant use of Meperidine with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in meperidine plasma concentration. Monitor patients receiving Meperidine and any CYP3A4 inhibitor or inducer.

Risks From Concomitant Use with Benzodiazepines Or Other CNS Depressants

• Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
  Reserve concomitant prescribing of Meperidine and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
  Limit dosage and duration to the minimum required.
  Follow patients for signs and symptoms of respiratory depression and sedation.

Concomitant Use of Meperidine with Monoamine Oxidase (MAO) Inhibitors

• Concomitant use of Meperidine with monoamine oxidase (MAO) inhibitors can result in coma, severe respiratory depression, cyanosis, and hypotension. Use of Meperidine with MAO inhibitors within last 14 days is contraindicated.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to:

• complete a REMS-compliant education program,
• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• consider other tools to improve patient, household, and community safety.