Licorice: Significant Interactions

2010

Controlled trials exist that have identified drug interactions. However, in most cases, the interactions are based on evidence of pharmacological activity, case reports or theoretical reasoning. The deglycyrrhizinated licorice form is considered safer and less likely to result in drug interactions.

ANTICOAGULANTS

Isoliquiritigenin inhibits platelet aggregation and glycyrrhizin inhibits prothrombin according to in vitro and in vivo tests. Whether the effect is clinically significant for licorice remains to be determined — use high doses with caution.

ANTIHYPERTENSIVES

High-dose glycyrrhizin taken long term can lead to increased blood pressure, thereby reducing drug efficacy. Caution — monitor blood pressure when high-dose licorice preparations are taken for longer than 2 weeks.

CHEMOTHERAPY (PACLITAXEL AND VINBLASTINE)

A constituent of licorice has demonstrated significant potentiation of paclitaxel and vinblastine chemotherapy in vitro. Observe — beneficial interaction is theoretically possible under medical supervision.

CORTICOSTEROIDS

Concurrent use of licorice preparations potentiates the effects of topical and oral corticosteroids (e.g. prednisolone). Some practitioners employ licorice to minimise requirements for or aid in withdrawal from corticosteroid medications. Beneficial interaction is possible under professional supervision, but patients should be monitored closely for corticosteroid excess.

DIGOXIN

Hypokalaemia increases sensitivity to cardiac glycoside drugs, therefore increased digoxin toxicity is possible when licorice is used in high doses for more than 2 weeks. A case report exists of congestive heart failure caused by digitalis toxicity in an elderly man taking a licorice-containing Chinese herbal laxative. Avoid long-term use of high-dose licorice preparations and digoxin concurrently.

ORAL CONTRACEPTIVE PILL

An increased risk of side-effects such as hypokalaemia, fluid retention and elevated blood pressure due to increased mineralocorticoid effect exists. This has been demonstrated in case reports — use this combination with caution when licorice is used in high dose or for more than 2 weeks and observe patients closely.

DIURETICS (INCLUDING LOOP, THIAZIDE AND POTASSIUM-SPARING)

Case reports exist in which patients experience hypokalaemia and hypertension with concomitant use of licorice and diuretics due to increased potassium excretion. Avoid long-term use of licorice and diuretics concurrently unless under professional supervision. Monitor potassium levels.

TESTOSTERONE

Licorice may decrease testosterone levels, although clinical tests have produced conflicting results. Observe and monitor patients for reduced testosterone effects.

DICLOFENAC SODIUM (NSAID)

In vitro studies have shown that the addition of GL enhanced the topical absorption of diclofenac sodium, which may be a beneficial interaction.

POTASSIUM

Licorice may reduce the effect of potassium supplementation. A case report exists of a 69-year-old female developing hypokalaemia while taking potassium supplements and a mouth freshener containing licorice concurrently. The daily intake of GA was estimated at 6-10 mg/day. In many cases potassium supplementation may be beneficial in reducing the hypokalaemic side-effects of licorice.

DRUGS METABOLISED BY LIVER ENZYMES CYP3A4, 2B6, 2C9, 2E1 OR 1A1

Licorice inhibits CYP3A4 in vitro, the glabridin constituent inhibits CYP2B6, 2C9 and 3A4 in vitro, GA inhibits expression of CYP2E1 in animal studies and glycyrrhizin enhances the detoxifying activity of CYP1A1. Until testing in humans can establish whether the effects are clinically significant and relevant to licorice in therapeutic doses, caution is advised if licorice is administered with drugs chiefly metabolised by these enzymes. (See chapter on Interactions for more information.)