From the Guidelines
Norco (hydrocodone and acetaminophen) is not typically associated with a high risk of serotonin syndrome.
Risk of Serotonin Syndrome
- The risk of serotonin syndrome is more commonly associated with opioids that have serotonin reuptake inhibitory activity, such as tramadol, tapentadol, and fentanyl 1.
- Hydrocodone, the opioid component of Norco, does not have significant serotonin reuptake inhibitory activity, and therefore, the risk of serotonin syndrome is lower compared to other opioids 1.
- However, it is still important to exercise caution when co-administering Norco with other medications that affect serotonin levels, such as monoamine oxidase inhibitors, SSRIs, SNRIs, and triptans, as the risk of serotonin syndrome cannot be entirely ruled out 1.
- The risk of serotonin syndrome can be mitigated by careful patient selection, dosing, and monitoring, as well as avoiding co-administration with other serotonergic medications whenever possible 1.
From the FDA Drug Label
Inform patients that hydrocodone bitartrate and acetaminophen tablets could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see PRECAUTIONS; Drug Interactions].
The risk of serotonin syndrome is associated with the concomitant administration of serotonergic drugs with hydrocodone and acetaminophen tablets. Patients should be warned of the symptoms of serotonin syndrome and instructed to seek medical attention immediately if symptoms develop. Patients should also inform their physicians if they are taking or plan to take serotonergic medications 2.
- Key points:
- Concomitant administration of serotonergic drugs increases the risk of serotonin syndrome
- Patients should be warned of the symptoms of serotonin syndrome
- Patients should seek medical attention immediately if symptoms develop
- Patients should inform their physicians of any serotonergic medications they are taking or plan to take
From the Research
Risk of Serotonin Syndrome with Norco (Hydrocodone and Acetaminophen)
- The risk of serotonin syndrome associated with Norco (hydrocodone and acetaminophen) is not directly stated in the provided studies, but it can be inferred that the combination of hydrocodone with certain serotonergic drugs may increase the risk of serotonin syndrome 3, 4.
- Hydrocodone is an opioid that may inhibit the serotonin transporter (SERT) and contribute to serotonergic toxicity, although its potency is not as high as other opioids such as tramadol and methadone 4.
- The combination of hydrocodone with cyclobenzaprine, a muscle relaxant with serotonergic properties, has been reported to cause serotonin syndrome in a patient with cerebral palsy 3.
- Other opioids, such as fentanyl, oxycodone, and methadone, have been associated with a higher risk of serotonin syndrome, especially when combined with selective serotonin reuptake inhibitors (SSRIs) or other serotonergic agents 5, 6, 4, 7.
- The clinical manifestations of serotonin syndrome include altered mental status, neuromuscular abnormalities, and autonomic dysfunction, and can be life-threatening if not recognized and treated promptly 5, 6, 7.