St. John's Wort and Carbamazepine Interaction
Yes, St. John's Wort interacts with carbamazepine, but the interaction is clinically distinct from most other drugs—St. John's Wort may actually decrease carbamazepine levels rather than enhance them, potentially leading to loss of seizure control. 1
Mechanism of Interaction
St. John's Wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), which accelerates the metabolism and elimination of substrate drugs, thereby reducing their therapeutic effectiveness. 2, 1
Carbamazepine is metabolized through the CYP450 system, making it susceptible to enzyme induction by St. John's Wort. 1
This contrasts with enzyme inhibitors (like grapefruit juice), which increase drug levels—St. John's Wort does the opposite by speeding up drug clearance. 1
Clinical Significance
The American Academy of Neurology notes that St. John's Wort may decrease levels of anticonvulsants including carbamazepine, phenytoin, and phenobarbital. 1
One major pharmacokinetic study found that St. John's Wort did not significantly alter carbamazepine pharmacokinetics in controlled settings. 3
However, the unpredictable degree of enzyme induction due to variable quality and quantity of constituents in St. John's Wort preparations makes this interaction clinically concerning. 4
Critical Management Considerations
Patients taking carbamazepine should avoid St. John's Wort or, if already taking both, require more frequent monitoring:
Monitor carbamazepine serum levels more frequently if St. John's Wort is initiated or discontinued. 1
Watch for breakthrough seizures or loss of seizure control, which may indicate subtherapeutic carbamazepine levels. 1
If St. John's Wort must be discontinued in a patient stabilized on both agents, carbamazepine levels may rise, requiring dose adjustment to prevent toxicity. 4
Additional Safety Concerns
St. John's Wort is not regulated by the FDA, and there is no standardization of content or potency, making the magnitude of any interaction unpredictable between different preparations. 2, 1
The American College of Cardiology and American Heart Association recommend avoiding St. John's Wort with medications metabolized by CYP3A4 and P-gp, which includes carbamazepine. 2, 1
Patients should always disclose St. John's Wort use to healthcare providers, particularly when taking anticonvulsants. 1
Common Pitfalls to Avoid
Do not assume all herbal supplements are safe with anticonvulsants—St. John's Wort has documented enzyme-inducing properties that can compromise seizure control. 1, 4
Do not rely on patient-reported "stable" medication regimens without specifically asking about herbal supplements, as patients often do not consider these "real medications." 1
Quality control issues with herbal preparations lack standardization, making interactions unpredictable even with the same brand over time. 5, 4