Herb-Drug Interactions: German Chamomile

Matricaria recutita L. (Asteraceae)

Synonym(s) and related species

ChamomiUa, Hungarian chamomile, Matricaria flower, Scented mayweed, Single chamomile, Sweet false chamomile, Wild chamomile.

ChamomiUa recutita (L.) Rauschert, ChamomiUa vulgaris SF Gray, Matricaria chamomilla L.

Pharmacopoeias

Chamomile (The United States Ph 32).

Constituents

The flowerheads of German chamomile contain essential oil composed mainly of (-)-alpha-bisabolol. Sesquiterpenes and proazulenes (e.g. matricarin and matricin) are also present. Chamazulene (1 to 15%), another volatile oil found in chamomile, is formed from matricin during steam distillation of the oil. Other constituents present in chamomile include flavonoids (apigenin, luteolin, quercetin, rutin), and the natural coumarins umbelliferone and its methyl ether, heniarin.

Use and indications

German chamomile is used for dyspepsia, flatulence and travel sickness, especially when the gastrointestinal disturbance is associated with nervous disorders. It is also used for nasal catarrh and restlessness. German chamomile is widely used in babies and children as a mild sedative, and to treat colic and teething pain. It has been used topically for haemorrhoids, mastitis and leg ulcers.

Pharmacokinetics

In vitro studies have found that a commercial ethanolic extract of Matricaria chamomilla and a crude Matricaria recutita essential oil extract inhibited the cytochrome P450 isoenzyme CYP3A4. However, the effects were weak when compared with the known potent CYP3A4 inhibitor ketoconazole.

A crude Matricaria recutita essential oil extract has also been found to moderately inhibit CYP1A2 in vitro.Similarly, a study using liver microsomes from rats pretreated with chamomile tea 2% for 4 weeks (Vita Fit Nutrition, made from the dried flower heads of Matricaria chamomilla and Matricaria recutita) found that CYP1A2 activity was reduced to 39%, when compared with the control group.

A crude Matricaria recutita essential oil extract had no significant effect on the cytochrome P450 isoenzymes CYP2C9 and CYP2D6.

For information on the pharmacokinetics of individual flavonoids present in German chamomile, see under flavonoids.

Interactions overview

An isolated case of bleeding in a patient taking warfarin and using chamomile products has been reported. No other relevant drug interactions have been found for German chamomile. For information on the interactions of individual flavonoids present in German chamomile, see under flavonoids.

German Chamomile + Food

No interactions found.

German Chamomile + Herbal medicines

No interactions found.

German Chamomile + Iron compounds

Chamomile tea (an infusion of Matricaria chamomilla) does not appear to affect iron absorption.

Evidence, mechanism, importance and management

A study in 13 healthy subjects found that chamomile tea (an infusion of Matricaria chamomilla) sweetened with panela (an unrefined cane sugar sweetener containing fructose) did not affect the absorption of iron from an iron-fortified bread, when compared with the absorption of iron from the bread alone. The tannin content of the chamomile tea was reported to be 24.5 mg in 100 mL. This is much less than the tannin content of black tea, which is known to reduce iron absorption. See Tea + Iron compounds. This level of tannins did not appear to affect iron absorption in this particular study and it would therefore appear that chamomile tea may be taken without impairing iron absorption.

German Chamomile + Warfarin

A single case report describes a woman stabilised on warfarin who developed a marked increase in her INR with bleeding complications 5 days after she started using two chamomile products.

Clinical evidence

A 70-year-old woman stabilised on warfarin with an INR of 3.6 started drinking 4 to 5 cups of chamomile tea (an infusion of Matricaria chamomilla) daily for chest congestion, and using a chamomile-based skin lotion 4 to 5 times daily for foot oedema. About 5 days later she developed ecchymoses and was found to have an INR of 7.9, a retroperitoneal haematoma and other internal haemorrhages.

Experimental evidence

No relevant data found.

Mechanism

German chamomile contains the natural coumarin compounds, umbelliferone and heniarin, However, these compounds do not possess the minimum structural requirements (a C-4 hydroxyl substituent and a C-3 non-polar carbon substituent) required for anticoagulant activity. German chamomile essential oil extracts do not appear to significantly affect the cytochrome P450 isoenzyme CYP2C9, the main isoenzyme involved in the metabolism of warfarin, but the effects of chamomile tea do not appear to have been studied.

Importance and management

This appears to be the first report of an interaction between warfarin and German chamomile. There seem to be no reports of German chamomile alone causing anticoagulation, and the natural coumarin constituents of German chamomile do not appear to possess anticoagulant activity, which might suggest that the risk of an additive effect is small. Furthermore, a pharmacokinetic basis for this interaction has not been established. Because of the many other factors influencing anticoagulant control, it is not possible to reliably ascribe a change in INR specifically to a drug interaction in a single case report without other supporting evidence. It may be better to advise patients to discuss the use of any herbal products that they wish to try, and to increase monitoring if this is thought advisable. Cases of uneventful use should be reported, as they are as useful as possible cases of adverse effects.