From the Guidelines
The combination of carbamazepine and Zyvox (linezolid) should be avoided due to the risk of serotonin syndrome, a potentially life-threatening condition. Carbamazepine is an anticonvulsant medication that can increase serotonin levels, while linezolid is an antibiotic that acts as a monoamine oxidase inhibitor (MAOI), preventing the breakdown of serotonin 1. When used together, excessive serotonin can accumulate in the brain, leading to symptoms such as agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremors, and in severe cases, seizures or death.
The potential for serious CNS reactions, such as serotonin syndrome, is a major concern when combining these medications 1. The risk of adverse events associated with the long-term use of linezolid, including peripheral neuropathy, optic neuritis, anemia, and leukopenia, further supports the need for caution when considering concomitant use with carbamazepine 1.
Key considerations for clinicians include:
- Avoiding concomitant use of other drugs that inhibit monoamine oxidases A or B
- Monitoring for signs of serotonin syndrome, especially during the first few weeks of combined therapy
- Selecting alternative antibiotics without MAOI properties whenever possible
- Choosing non-serotonergic anticonvulsants for patients on linezolid who require seizure control
- Being aware of the potential for adverse events associated with long-term linezolid use.
Given the potential risks, alternative treatment options should be prioritized to minimize the risk of morbidity, mortality, and compromised quality of life.
From the FDA Drug Label
Other strong inducers of hepatic enzymes (e. g. carbamazepine, phenytoin, phenobarbital) could cause a similar or smaller decrease in linezolid exposure The interaction between Carbamazepine and Zyvox (linezolid) may result in a decrease in linezolid exposure due to the strong hepatic enzyme-inducing properties of Carbamazepine.
- This could potentially lead to reduced efficacy of Zyvox.
- The clinical significance of this interaction is unknown 2.
From the Research
Implications of Interaction between Carbamazepine and Zyvox (Linezolid)
- The interaction between Carbamazepine and Zyvox (Linezolid) is not directly addressed in the provided studies, which primarily focus on the interactions between Linezolid and selective serotonin reuptake inhibitors (SSRIs) or other serotonergic agents 3, 4, 5, 6.
- However, it is known that Carbamazepine is a potent inducer of cytochrome P450 enzymes, particularly CYP3A4, which can affect the metabolism of various drugs 7.
- Linezolid, on the other hand, is a weak monoamine oxidase inhibitor and can interact with serotonergic agents to increase the risk of serotonin syndrome 3, 4, 5, 6.
- Although there is no direct evidence of an interaction between Carbamazepine and Linezolid, the concomitant use of these drugs may require careful monitoring due to their potential effects on each other's metabolism and the risk of serotonin syndrome 7.
- Clinicians should be aware of the potential risks and monitor patients closely for signs of serotonin syndrome or other adverse effects when using Carbamazepine and Linezolid together, although the exact implications of this interaction are not well-documented in the provided studies 3, 4, 7, 5, 6.