Herb-Drug Interactions: Hawthorn

Crataegus laevigata (Poir.) DC, Crataegus monogyna Jacq. (Rosaceae)

Synonym(s) and related species

Crataegus, Haw, May, Weissdorn, Whitethorn.

Crataegus oxyacantha auct, Crataegus oxyacanthoides Thuill.

Pharmacopoeias

Hawthorn Berries (British Ph 2009, European Ph 2008); Hawthorn Leaf and Flower (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4); Hawthorn Leaf and Flower Dry Extract (British Ph 2009, European Ph 2008); Hawthorn Leaf with Flower (US Ph 32); Quantified Hawthorn Leaf and Flower Liquid Extract (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4).

Constituents

The leaves and flowers of hawthorn are usually standardised to their flavonoid content, and the berries may be standardised to their procyanidin content. Other flavonoids present include quercetin, isoquercetin and their glycosides, and rutin. Other constituents include catechins and epicatechin dimers, polyphenolic acid derivatives including chlorogenic and caffeic acids, phenethylamine, dopamine, and ursolic and oleanolic acid triterpenenoid derivatives.

Use and indications

Hawthorn extracts are used as a cardiotonic, mild anti-hypertensive and antisclerotic.

Pharmacokinetics

No relevant pharmacokinetic data found. For information on the pharmacokinetics of individual flavonoids present in hawthorn, see under flavonoids.

Interactions overview

The safety of hawthorn extracts was investigated in a comprehensive systematic review, which included data up to January 2005 from the WHO, relevant medical journals and conference proceedings. The investigators found that 166 adverse events were reported in 5577 patients from 24 clinical studies, and 18 cases of adverse events were reported via the WHO spontaneous reporting scheme. None of these involved drug interactions. In the clinical studies assessed, the daily dose and duration of treatment with hawthorn preparations ranged from 160 to 1800mg and from 3 to 24 weeks, and the extracts most used contained leaves and flowers and were WS 1442 (standardised to 18.75% oligomeric procyanidins) and LI 132 (standardised to 2.25% flavonoids). Other studies do not appear to have identified any clinically significant drug interactions.

For information on the interactions of individual flavonoids present in hawthorn, see under flavonoids.

Hawthorn + Antidiabetics

Hawthorn does not appear to affect the glycaemic control in patients taking conventional antidiabetic drugs.

Clinical evidence

In a randomised study, 80 patients with type 2 diabetes taking antidiabetics (including metformin, gliclazide and/or low-dose insulin) with or without antihypertensives were given hawthorn extract 600 mg twice daily, or placebo, for 16 weeks. There was no difference between the two groups in measures of glycaemic control (fasting glucose, glycosylated haemoglobin and fructosamine) at 16 weeks. The hawthorn extract used in this study, LI 132, contained dried flowering tops and was standardised to 2.2% flavonoids.

Experimental evidence

No relevant data found.

Mechanism

No mechanism expected.

Importance and management

Evidence is limited to this one study. However, as no alteration in glycaemic control was reported, no interventions are deemed necessary in patients taking antidiabetics and hawthorn extract.

Hawthorn + Antihypertensives

Limited evidence suggests that there may be additive blood pressure-lowering effects if hawthorn is taken with conventional antihypertensives, but the effects are small.

Clinical evidence

In a randomised study, 80 patients with type 2 diabetes, of whom 71% were taking antihypertensives (including ACE inhibitors, calcium-channel blockers, beta blockers and/or diuretics), were given hawthorn extract 600 mg twice daily or placebo for 16 weeks. The group given hawthorn extract (39 of 40 patients assessed) had a small additional 2.6mmHg reduction in diastolic blood pressure compared with no change in the placebo group. The 3.6mmHg decline in systolic blood pressure in the hawthorn group was not statistically significant. The hawthorn extract used in this study, LI 132, contained dried flowering tops and was standardised to 2.2% flavonoids.

Experimental evidence

No relevant data found.

Mechanism

Little known. Additive blood pressure-lowering effects might occur.

Importance and management

Evidence appears to be limited to this one clinical study. Although hawthorn extract caused a reduction in diastolic blood pressure in patients, many of whom were taking antihypertensives, the effect was small. As such, it is unlikely that clinically important hypotension would occur if hawthorn is added to existing antihypertensive treatment.

Hawthorn + Digoxin

Hawthorn does not appear to affect digoxin levels.

Clinical evidence

In a randomised, crossover study, 8 healthy subjects were given hawthorn extract 450 mg twice daily with digoxin 250 micrograms daily for 21 days, or digoxin 250 micrograms alone daily for 10 days. While digoxin levels tended to be lower when hawthorn was given (the biggest difference being a 23% reduction in the trough level), these reductions were not statistically significant. There was no change in ECG effects or heart rate, and the combination was well tolerated. The hawthorn extract used in this study, WS 1442, contained an extract of leaves with flowers standardised to 84.3 mg of oligomeric procyanidines.

Experimental evidence

No relevant data found.

Mechanism

Little known. It was thought that flavonoids in hawthorn might have an effect on P-glycoprotein, of which digoxin is a substrate. In addition, it is possible that the cardioactive constituents of hawthorn might increase the effect of digoxin on cardiac contractility.

Importance and management

This study appears to be the only evidence reported. It suggests that, despite theoretical concerns that hawthorn may affect treatment with digoxin, in practice there appears to be no clinically relevant alteration in digoxin levels or effects. It therefore appears that hawthorn can be given to patients taking digoxin without the need for further monitoring.

Hawthorn + Food

No interactions found.

Hawthorn + Herbal medicines

No interactions found.