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Hydrocodone is a potent analgesic commonly prescribed for moderate-to-severe pain management in postoperative settings, trauma patients, and individuals with cancer. When combined with acetaminophen, hydrocodone demonstrates increased efficacy without significantly altering the adverse effect profile, as evidenced by randomized studies. This combination is also frequently used as an antitussive agent. This activity reviews the indications, mechanism of action, pharmacokinetics, methods of administration, and potential adverse effects of hydrocodone/acetaminophen. Additionally, it outlines important precautions, contraindications, monitoring guidelines, and toxicity risks associated with this drug combination. By improving the interprofessional team’s understanding of hydrocodone/acetaminophen, this program aims to optimize patient care and safety in pain management. Objectives: Identify the mechanism of action of hydrocodone/acetaminophen. Determine the FDA-approved uses for initiating hydrocodone/acetaminophen therapy. Assess the adverse event profile and contraindications to using hydrocodone/acetaminophen. Communicate interprofessional team strategies for improving care coordination to advance hydrocodone/acetaminophen therapy, improve outcomes, and minimize adverse events and misuse, especially in light of the ongoing opioid crisis. Access free multiple choice questions on this topic.

Acetaminophen may cause fatal hepatic necrosis in patients taking more than 4 g per day. Furthermore, large doses may cause difficulty breathing. During an overdose, activated charcoal should be the first attempted intervention before N-acetylcysteine (NAC). The serum acetaminophen level should be obtained promptly for patients presenting 4 hours or longer after the ingestion.[13] For more information, please refer to StatPearls' companion resource, Acetaminophen Toxicity. Hydrocodone intake may lead to life-threatening respiratory depression, especially if taken together with benzodiazepines or other CNS depressants. During an overdose, the priority is to protect the airways. Patients may require invasive ventilation. The opioid antagonists nalmefene and naloxone are antidotes that should be readily available for patients with respiratory depression. Opioid antagonists should be avoided in the absence of clinically significant respiratory or circulatory depression. Additionally, there is a high risk of precipitating acute opioid withdrawal in a patient who is physically dependent on opioids.

Without proper barriers and monitoring for the detrimental effects of hydrocodone and acetaminophen intoxication, the morbidity and mortality of patients using opioids can be quite significant. The drug information sheet from the manufacturer emphasizes the importance of warning patients about the misuse of and addiction to hydrocodone and acetaminophen, which can lead to overdose and death. Multiple efforts point toward reducing prescription abuse and misuse. The mitigation of opioid overdose and misuse risk starts from the system-level intervention by clinicians prescribing narcotics. In addition, the Prescription Drug Monitoring Program and Medicaid managed care lock-in program require that patients receive all scripts from a single prescriber. Although over 55% dropped from the program, the proportion of stable patients (ie, patients exclusively filled with 1 prescriber) increased from 31% to 78% at 36 months.[14] Pharmacists should use formulary management tools to address both opioid overprescribing and overdose. One example is a prior authorization requirement placed by the insurance companies to verify the necessary medication. Cochran et al conducted a retrospective cohort study evaluating the effects of prior authorization on the rate of abuse and overdose of patients enrolled in the Pennsylvania Medicaid program from 2010 to 2012. The study demonstrated that plans with prior authorization requirements had lower rates of use disorder and overdose.[15]