Hydrocodone Bitartrate and Acetaminophen

WARNING: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Risk of Medication Errors

Ensure accuracy when prescribing, dispensing, and administering Hydrocodone Bitartrate and Acetaminophen Oral Solution. Dosing errors due to confusion between mg and mL, and other Hydrocodone Bitartrate and Acetaminophen Oral Solutions of different concentrations can result in accidental overdose and death [see WARNINGS, DOSAGE AND ADMINISTRATION].

Addiction, Abuse, and Misuse

Hydrocodone Bitartrate and Acetaminophen Oral Solution 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 Bitartrate and Acetaminophen Oral Solution, and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS ].

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 [see WARNINGS]. 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.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of Hydrocodone Bitartrate and Acetaminophen Oral Solution. Follow patients for signs of respiratory depression, especially during initiation of Hydrocodone Bitartrate and Acetaminophen Oral Solution or following a dose increase [see WARNINGS].

Accidental Ingestion

Accidental ingestion of Hydrocodone Bitartrate and Acetaminophen Oral Solution, especially by children, can result in a fatal overdose of Hydrocodone Bitartrate and Acetaminophen Oral Solution [see WARNINGS].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of Hydrocodone Bitartrate and Acetaminophen Oral Solution 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].

Cytochrome P450 3A4 Interaction

The concomitant use of Hydrocodone Bitartrate and Acetaminophen Oral Solution with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which 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. Follow patients receiving Hydrocodone Bitartrate and Acetaminophen Oral Solution and any Cytochrome P450 3A4 inhibitor or inducer for signs and symptoms of respiratory depression and sedation [see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS; Drug Interactions].

Hepatotoxicity

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [see WARNINGS, OVERDOSAGE].

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 [see WARNINGS, PRECAUTIONS; Drug Interactions].

• Reserve concomitant prescribing of Hydrocodone Bitartrate and Acetaminophen Oral Solution and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.