What this means in practice
Digoxin has a narrow safe range and is monitored by blood test, so the practical point is timing. A level checked in the first few days of starting St John's Wort will look normal and mean nothing; the same is true in reverse when stopping. Tell whoever manages the digoxin, on both occasions.
What people say
If a herb were going to interfere with a heart drug, you would notice something on the first day. It either does something or it does not.
What the evidence supports
The first dose of St John's Wort changed digoxin levels not at all. By day 10 of continuous use, exposure over 24 hours had fallen by 25%, trough levels by 33% and peak levels by 26%, and the effect was still growing (Johne 1999). In a 96-volunteer study of ten different St John's Wort products, the size of the drop tracked hyperforin content: hyperforin-rich extract cut exposure by 24.8%, while tea, juice, oil and hyperforin-free extract produced no significant change at all (Mueller 2004). A separate study measured a 1.4-fold rise in the P-glycoprotein pump in gut tissue after two weeks (Durr 2000).
How it is supposed to work
P-glycoprotein is a pump in the gut wall that throws absorbed drug back into the intestine. Hyperforin increases how much of that pump is present, so less digoxin is absorbed and blood levels fall.
Which way it runs
One-directional. St John's Wort lowers digoxin levels. Digoxin is barely metabolised by CYP3A4, so this interaction runs almost entirely through the P-glycoprotein pump rather than through the liver enzyme, which makes digoxin the cleanest human readout of that half of the mechanism.
What is still missing
The first day is exactly when nothing happens, and that is the trap. The interaction is built rather than triggered: the body has to manufacture more pump before anything changes, so a week of feeling fine is what the interaction looks like while it is forming.
Sources
- Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum)Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I, 1999
- Effect of St John's wort dose and preparations on the pharmacokinetics of digoxinMueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B, 2004
- St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4Durr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K, 2000
- St John's wort (Hypericum perforatum): drug interactions and clinical outcomesHenderson L, Yue QY, Bergquist C, Gerden B, Arlett P, 2002