Addition, Abuse, and Misuse; Life-Threatening Respiratory Depression; Accidental Ingestion; Neonatal Opioid Withdrawal Syndrome; Interaction with Alcohol; and Cytochrome P450 3A4 Interaction; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants; Risk Evaluation and Mitigation Strategy (REMS)

Addiction, Abuse, and Misuse

• Hydrocodone bitatrate ER 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 Hydrocodone bitatrate ER and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1)].
• 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 Hydrocodone bitatrate ER. Monitor for respiratory depression, especially during initiation of Hydrocodone bitatrate ER or following a dose increase. Instruct patients to swallow Hydrocodone bitatrate ER capsules whole; crushing, chewing, or dissolving Hydrocodone bitatrate ER  can cause rapid release and absorption of a potentially fatal dose of hydrocodone [see Warningsand Precautions (5.2)].
• 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.

Accidental Ingestion

• Accidental ingestion of even one dose of Hydrocodone bitatrate ER , especially by children, can result in a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome

• Prolonged use of Hydrocodone bitatrate ER  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 [see Warnings and Precautions (5.3)].

Interaction with Alcohol

• Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking Hydrocodone bitatrate ER . The co-ingestion of alcohol with Hydrocodone bitatrate ER  may result in increased plasma levels and a potentially fatal overdose of hydrocodone [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3)].

Cytochrome P450 3A4 Interaction

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

Risk From Concomitant Use with Benzodiazepines or Other CNS Depressants

• Concomitant use of opioids with benzodiazepine or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

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.