Addiction, Abuse, and Misuse:  Life-threatening Respiratory Depression; Accidental Ingestion; Neonatal Opioid Withdrawal Syndrome; and Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants; Risk Evaluation and Mitigation Strategy (REMS)

Addiction, Abuse, and Misuse

• Morphine 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 Morphine, and monitor all patients regularly for the development of these behaviors or 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 Morphine. Monitor for respiratory depression, especially during initiation of Morphine or following a dose increase. Instruct patients to swallow [Tradename] (formulation; e.g., tablets, capsules) whole; crushing, chewing, or dissolving Morphine (formulation) can cause rapid release and absorption of a potentially fatal dose of (active opioid).
• 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.
• Morphine Sulfate Oral Solution 20 mg/ml is for use onlu in opioid-tolerant adult patients. The safety and effectiveness of Morphine Sulfate Oral Solution 20 mg/mL have not been established in pediatric patients.

Accidental Exposure

• Accidental [ingestion/exposure] of even one dose of [Tradename], especially by children, can result in a fatal overdose of (active opioid).

Neonatal Opioid Withdrawal Syndrome

• Prolonged use of Morphine 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.

Interaction with Alcohol (This subheading and text should be included in the boxed warning only for products that have an interaction with alcohol.)

• Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking Morphine. The co-ingestion of alcohol with Morphine may result in increased plasma levels and a potentially fatal overdose of (active opioid).

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.

THIS IS AN EXAMPLE OF BOX WARNING DATA FOR MORPHINE SULFATE PRODUCTS. REFER TO SPECIFIC PRODUCT PACKAGE INSERT FOR SPECIFIC DETAILS