A 68 y/o patient with moderate stable CHF (NYHA class III) is currently on a 4 drug cocktail (including furosemide, digoxin, lisinopril, and low-dose metoprolol). He's been stable and doing well on this medication combo for over 6 months. He was relatively asymptomatic during his last visit and his labs were WNL. He's less than happy with the current medical system and his condition.  On his own, he decides to try some herbal and alternative medications available at a local health food store.

During his next visit his serum digoxin level was subtherapeutic and he had been noticing increased swelling of his lower extremities. He claims compliance with his meds and diet. Pills counts appear to confirm his claims.

What do you do? Increase his current meds? Add another agent? Something else?

Most people would do a thorough H&P and physical examlooking for some precipitating physical cause of his worsening heart failure such as MI, sodium/dietary indiscretion, PE, arrythmia, etc. Assuming no precipitating physical cause is found, one should investigate drug compliance, including over-the-counter (OTCs) meds as well as herbal therapies. Routine queries about OTC and herbals should be included in patient histories, esp nowadays with an ever increasing use of herbals and alternative medicine..

Specifically, St John's Wort (Hypericum perforatum) has been shown in one small study to reduce digoxin serum levels from 25 to 33%. A small placebo-controlled parallel study compared the effects of placebo (n=12) vs St John's Wort (n=13) on the pharmacokinetics of digoxin. After 10 days of co-administration of digoxin and St John's Wort, the patients on the combination showed decreased digoxin AUC 0-24hrs by 25%, decreased peak plasma concentration by 26%, decreased trough plasma concentration by 19%, and a 33% decrease in digoxin plasma concentration 24 hours after the last dose.

The exact mechanism for this interaction is unclear. St John's Wort is metabolized via several CYP-450 isoenzymes and this may be responsible for it's interactions with other drugs such as theophylline, cyclosporine, indanivir, etc.

A useful reference website is the Center for Education and Research on Therapeutics (CERT). You can reach this site using several addresses such as www.drug-interactions.com, www.gu-cert.com, or www.georgetowncert.org. A handy pocket card can be printed off of this website too. Check it out soon. This site also has an international registry for drug-induced arrhythmias (www.QTdrugs.org).

References:

- http://www.georgetowncert.org/interactions_article2.html
- Johne A, Brockmöller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharmacokinetic interaction of digoxin with an herbal extract from St. John's wort (Hypericum perforatum). Clin.Pharmacol.Ther. 1999;66:338-45.

- Salphati L, Benet LZ. Metabolism of digoxin and digoxigenin digitoxisides in rat liver microsome: involvement of cytochrome P4503A. Xenobiotica 1999;29:171-85.