From the Guidelines
Medications that inhibit CYP2D6, such as certain antidepressants or antipsychotics, can decrease the efficacy of codeine as an analgesic and/or antitussive (cough suppressant). Codeine is a prodrug that requires metabolism by CYP2D6 to active metabolites, such as morphine, in order to be effective as an analgesic and antitussive 1. The addition of medications that inhibit CYP2D6 can reduce the amount of prodrug that is converted to active drug, resulting in inadequate analgesia 1. This is because the inhibition of CYP2D6 slows down the conversion of codeine to its active metabolite, morphine, leading to reduced efficacy as a pain reliever and cough suppressant. Patients taking codeine and a CYP2D6 inhibitor concurrently may require closer monitoring for adequate symptom control or consideration of alternative analgesics not affected by enzyme inhibition 1.
Some key points to consider when prescribing codeine to patients include:
- Codeine and tramadol are prodrugs that require metabolism by CYP2D6 to active metabolites in order to be effective analgesics 1
- The addition of medications that inhibit CYP2D6 in the perioperative period can reduce the amount of prodrug that is converted to active drug, resulting in inadequate analgesia 1
- Patients receiving long-term opioid therapy will likely need higher than usual opioid dosing to achieve pain control or will need adjunctive nonopioid analgesia perioperatively 1
- Avoid meperidine, codeine, and morphine (due to active metabolites and accumulation) in renal insufficiency (GFR <30 mL/min/1.73 m2) and ESRD 1
It is essential to carefully evaluate the medication list of patients taking codeine and consider potential interactions with CYP2D6 inhibitors to ensure optimal pain management and minimize the risk of inadequate analgesia 1.
From the Research
Medications that Decrease the Efficacy of Codeine
- Certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs), can decrease the efficacy of codeine as an analgesic and/or antitussive (cough suppressant) by inhibiting the cytochrome 2D6 enzyme, which is necessary for codeine to be metabolized into morphine 2.
- Other medications that inhibit the cytochrome 2D6 enzyme may also decrease the efficacy of codeine, although specific examples are not provided in the available evidence.
Mechanism of Interaction
- The interaction between codeine and certain medications, such as antidepressants, occurs through the inhibition of the cytochrome 2D6 enzyme, which is necessary for the bioactivation of codeine into morphine 2.
- This inhibition can lead to inadequate analgesia and reduced efficacy of codeine as a cough suppressant.
Clinical Implications
- The concomitant prescription of codeine and medications that inhibit the cytochrome 2D6 enzyme, such as certain antidepressants, should be avoided 2.
- Healthcare professionals should be aware of the potential interactions between codeine and other medications and take steps to prevent problematic occurrences of concomitant prescription administration 2.