What this means in practice
Anyone on tacrolimus should not start St John's Wort, and should tell the transplant team if they already have. Stopping matters as much as starting: levels drift back up over the following weeks, so a dose set while on the herb becomes too high once it is out.
What people say
Herbal, over the counter, and not a real medicine, so it does not need mentioning at a transplant clinic appointment.
What the evidence supports
In 10 stable kidney transplant patients, two weeks of St John's Wort cut dose-corrected tacrolimus exposure from 180 to 75.9 nanograms per millilitre per hour and forced the median daily dose from 4.5 mg up to 8.0 mg to hold therapeutic levels. Two weeks after stopping the herb the dose was still at 6.5 mg, above where it started (Mai 2003). The US prescribing information for tacrolimus lists St John's Wort with rifampin and the enzyme-inducing epilepsy drugs as a strong CYP3A inducer that increases the risk of rejection, and instructs prescribers to raise the dose and monitor blood levels (Prograf, SPL version 30).
How it is supposed to work
Tacrolimus is cleared almost entirely by CYP3A4, which hyperforin switches on. Clearance rises, blood levels fall, and the dose has to go up to compensate. The effect does not stop the day the herb does, because the extra enzyme takes time to disappear.
Which way it runs
One-directional. St John's Wort lowers tacrolimus levels; the reverse does not happen. Mycophenolic acid, the drug given alongside tacrolimus in most transplant regimens, was measured in the same study and was unaffected, so this is specific to tacrolimus rather than general to immunosuppressants.
What is still missing
Calling it not a real medicine gets the pharmacology exactly backwards. The FDA groups it with rifampin, one of the most powerful enzyme inducers in the pharmacy, and the measured effect in patients was a near doubling of the dose needed.
Sources
- Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patientsMai I, Stormer E, Bauer S, Kruger H, Budde K, Roots I, 2003
- PROGRAF (tacrolimus) capsules, injection and granules: US FDA prescribing informationAstellas Pharma US, Inc., SPL version 30
- Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observationsBorrelli F, Izzo AA, 2009