Herbal Drug Interactions

Herbal drug interactions occur when a herbal product alters the effect or handling of a conventional medicine taken at the same time, or vice versa. Because herbal preparations contain many constituents and are widely used alongside prescription drugs, such interactions are an important safety concern. They may be pharmacokinetic — changing how a co-administered drug is absorbed, metabolized, or eliminated — or pharmacodynamic — adding to or opposing its effect at the target.

Definition

A herbal drug interaction is a modification of the pharmacokinetics or pharmacodynamics of a conventional medicine (or of a herbal constituent) that results from the concurrent use of a herbal product.

Scope

This entry covers the mechanisms and appraisal of interactions between herbal products and conventional medicines, including enzyme and transporter modulation and pharmacodynamic additivity or antagonism, with St John's wort as a well-studied example. It is reference material on the topic; it gives no dosing advice and is not a basis for managing any individual's medicines.

Core questions

• By what mechanisms can a herbal product alter the effect of a conventional medicine?
• How do herbal constituents induce or inhibit drug-metabolizing enzymes and transporters?
• What distinguishes pharmacokinetic from pharmacodynamic herbal drug interactions?
• How is the evidence for a suspected herbal drug interaction evaluated?

Key concepts

• Pharmacokinetic versus pharmacodynamic interactions
• Cytochrome P450 induction and inhibition
• Drug transporter modulation (e.g., P-glycoprotein)
• Additive or antagonistic pharmacodynamic effects
• Complexity and variability of multi-constituent products
• Causality assessment and evidence quality

Mechanisms

Herbal products can alter a co-administered drug's pharmacokinetics by changing the activity of drug-metabolizing enzymes or transporters. The classic example is St John's wort, which induces cytochrome P450 3A4 and can lower the plasma concentrations of many drugs metabolized by that enzyme (Markowitz et al., 2003). Interactions may also be pharmacodynamic, when a herbal constituent adds to or opposes a drug's effect at a shared target. Because herbal preparations are mixtures whose constituents themselves interact, predicting net effects is difficult (Williamson, 2001), and systematic review of the clinical literature is needed to separate well-documented interactions from weak or anecdotal reports (Izzo & Ernst, 2009).

Clinical relevance

Awareness of herbal drug interactions is part of medication safety and evidence appraisal, since concurrent use of herbal and conventional products is common. This entry describes how such interactions arise and are evaluated in the literature; it provides no dosing or individualized treatment advice, and decisions about a person's medicines belong to qualified clinicians.

History

Reports of interactions between herbal products and prescription drugs accumulated through the 1990s and 2000s, with St John's wort's induction of cytochrome P450 3A4 becoming a defining case (Markowitz et al., 2003). Systematic reviews then sought to organize and weigh the evidence across many herbs and drugs, distinguishing established interactions from poorly supported claims (Izzo & Ernst, 2009).

Debates

How strong is the evidence for many reported herbal drug interactions?

Much of the literature rests on case reports or small studies, and a recurring methodological question is how to grade causality and clinical significance when the herbal product is a variable, multi-constituent mixture.

Key figures

• Angelo A. Izzo
• Edzard Ernst
• John S. Markowitz
• Elizabeth M. Williamson

Seminal works

• izzo-ernst-2009
• markowitz-2003

Frequently asked questions

What is the difference between a pharmacokinetic and a pharmacodynamic herbal drug interaction?

A pharmacokinetic interaction changes how much of a drug is present by altering its absorption, metabolism, or elimination; a pharmacodynamic interaction changes the drug's effect at its target without necessarily changing its concentration.

Why is St John's wort a frequently cited example?

It induces the enzyme cytochrome P450 3A4, which metabolizes many medicines, so it can reduce their blood concentrations and effect when taken together.