Table 4: Hydrocodone Drug-Drug Interactions
| Interacting Drug | Interaction | Recommendation | Clinical Significance Level |
|---|---|---|---|
| anticholinergics (e.g., antidiarrheals) | co-administration may lead increased risk of urination retention, severe constipation, including paralytic ileus, especially with chronic use, and CNS depression due to additive anticholinergic effects | observe for chronic constipation, urinary retention, and CNS depression; adjust doses and/or discontinue therapy as needed | 2-major (CP) |
| CYP3A4 inducers (e.g., rifampin, barbiturates) | adjunctive use may result in decreased hydrocodone plasma levels/reduced therapeutic effects, including withdrawal, as hydrocodone is CYP3A4 substrate | monitor for effective therapeutic effects; modify doses as necessary | major (DrugReax) 3-moderate (CP) |
| CYP3A4 inhibitors | concurrent administration with CY3A4 inhibitors may result in increased hydrocodone serum levels and the potential for enhanced pharmacologic/ adverse effects through inhibition of CYP3A4-mediated hydrocodone metabolism | monitor for effective analgesia and signs/symptoms of adverse effects (e.g., enhanced sedation, respiratory depression); modify doses as necessary | major (DrugReax) 2-major (CP) |
| gabapentin | potential for decreased hydrocodone peak concentrations and AUC with concomitant gabapentin-hydrocodone administration in dose-dependent fashion; minor increases in gabapentin AUC | observe patients for decreased hydrocodone efficacy or additive drowsiness | minor (DrugReax) 3-moderate (CP) |
| monoamine oxidase inhibitors (MAOIs) | combined administration may result in severe, unpredictable additive effects | although no specific adverse interactions have been reported with the hydrocodone-MAOI combination, hydrocodone should not be administered in patients who have received MAOIs within 14 days | major (DrugReax) 2-major (CP) |
| opiate agonist/ antagonists (OAAs) (e.g., buprenorphine, pentazocine) | concomitant administration may result in partial blockade of hydrocodone pharmacologic effects and may precipitate a withdrawal syndrome in some patients requiring chronic hydrocodone therapy; antagonist effects are more likely to occur when OAAs used concurrently with low to moderate doses of a pure opioid agonist; adjunctive therapy may be required in some instances, which may result in additive CNS depressant, respiratory, and hypotensive effects | patients requiring concurrent therapy with hydrocodone and a mixed OAA should be monitored for enhanced or attenuated pharmacologic effects, which may necessitate hydrocodone dosage adjustments and/or pharmacotherapy modifications | major (DrugReax) 2-major (CP) |
| opiate agonists (OAs) | concurrent administration of pure OAs and narcotic analgesics like hydrocodone, or administration of OAs within 7 to 10 days of narcotic analgesic therapy may induce an acute abstinence syndrome | unless clinically significant respiratory depression is present, OAs should not be administered concurrently with hydrocodone | contraindicated (DrugReax) 2-major (CP) |
Legend:
- *CP = Clinical Pharmacology
- AUC = area under the curve
- CNS = central nervous system