Hydrocodone is primarily used to treat severe chronic pain that requires opioid analgesia and is not effectively treated by nonopioid alternatives. Hydrocodone is used in combination formulations to treat nonproductive cough in adults and has antitussive properties. Hydrocodone functions as an opioid receptor agonist and activates mu-opioid receptors to produce analgesic effects. In addition, hydrocodone activates delta- and kappa-opioid receptors as the plasma drug concentration increases beyond the starting doses. This activity focuses on single-ingredient hydrocodone for pain relief. This activity outlines the indications, mechanism of action, significant adverse effects, contraindications, monitoring, toxicity, and other critical elements of hydrocodone therapy in the clinical setting. These details are essential for the interprofessional healthcare teams responsible for managing the care of patients with pain and related conditions and sequelae.

Objectives:

• Identify appropriate indications for hydrocodone therapy, distinguishing between its use in severe chronic pain and nonproductive cough in adults.
• Assess patients for pain relief while monitoring both the effectiveness of hydrocodone and any potential adverse effects, signs of misuse, or addiction.
• Select the most appropriate formulation and strength of hydrocodone based on the patient's pain intensity, duration, and individual needs, considering factors such as age, renal or hepatic impairment, and potential drug interactions.
• Collaborate with an interprofessional healthcare team, including physicians, pharmacists, mental health counselors, pain management specialists, and addiction specialists, to optimize patient outcomes and ensure comprehensive care.

Adverse Effects

The most common adverse effects of hydrocodone include frequent constipation and nausea. Additional adverse effects of hydrocodone include the following:

• Respiratory: Severe respiratory depression, shortness of breath, respiratory tract infection 
• Cardiovascular: Hypotension, bradycardia, and peripheral edema 
• Neurologic: Headache, chills, anxiety, sedation, insomnia, dizziness, drowsiness, and fatigue 
• Dermatologic: Pruritus, diaphoresis, and rash
• Gastrointestinal: Vomiting, dyspepsia, gastroenteritis, constipation, and abdominal pain Genitourinary: Urinary tract infection and urinary retention associated with prostatic hypertrophy 
• Otic: Tinnitus and sensorineural hearing loss (SNHL)
• Endocrine: Secondary adrenal insufficiency

Drug-Drug Interactions

• Concurrent use of hydrocodone with central nervous system depressants, such as alcohol, benzodiazepines, barbiturates, or other opioids, can result in profound sedation and respiratory depression; therefore, these combinations must be avoided.

• Medications that induce (eg, rifampin, phenytoin, and carbamazepine) or inhibit (eg, cimetidine, fluoxetine, and ritonavir) cytochrome enzymes should be closely monitored. This can result in significant variations in hydrocodone plasma concentrations.

• The combination of hydrocodone and acetaminophen poses a potential drug interaction with warfarin, causing an elevated international normalized ratio (INR) and an increased risk of bleeding.

• Concurrent use of hydrocodone with CYP3A4 inhibitors or discontinuation of CYP3A4 inducers can result in a fatal overdose of hydrocodone. Consequently, it is crucial to avoid this combination.

Contraindications

Contraindications to hydrocodone use include:

• Hypersensitivity to hydrocodone or any component of the formulation
• Bronchial asthma in an unmonitored setting
• Known or suspected gastrointestinal obstruction, including paralytic ileus [
• Significant respiratory depression 
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• Monitoring

Legal Considerations

Owing to widespread abuse and misuse concerns, the Drug Enforcement Agency (DEA) reclassified hydrocodone combination products from Schedule III to Schedule II drugs in October 2014. A study indicates that this rescheduling is associated with a substantial decrease in hydrocodone overdose rates