Herb-Drug Interactions: Melilot

2011

Melilotus offidnalis (L.) Pall. (Fabaceae)

Synonym(s) and related species

King’s clover, Sweet clover, Ribbed melilot, Yellow melilot, Yellow sweet clover.

Melilotus arvensis Wallr.

Pharmacopoeias

Melilot (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4).

Constituents

The main active constituents of melilot are natural coumarin and its derivatives, melilotin, melilotol, dihydrocoumarin, umbelliferone and scopoletin, which are formed on drying from the glycoside melilotoside. If spoilage and subsequent fermentation occur, some coumarin derivatives can be transformed into the potent anticoagulant dicoumarol (bishydroxycoumarin). Other constituents present are flavo-noids (including quercetin) and a number of saponins.

Use and indications

Melilot is used mainly to treat inflammation, oedema and capillary fragility.

Pharmacokinetics

No relevant pharmacokinetic data for melilot found. For information on the pharmacokinetics of individual flavo-noids present in melilot, see under flavonoids.

Interactions overview

Two cases describe bleeding and a raised INR in patients taking a tea and using a topical cream containing melilot, but an interaction has not been established. For information on the interactions of individual flavonoids present in melilot, see under flavonoids.

Melilot + Food

No interactions found.

Melilot + Herbal medicines

No interactions found.

Melilot + Warfarin and related drugs

The INR of a patient taking acenocoumarol was increased after she used a melilot-containing topical cream, and a woman who had been drinking large quantities of a herbal tea containing melilot developed a prolonged prothrombin time.

Clinical evidence

A 66 year old taking acenocoumarol, levothyroxine and prazepam had an increase in her INR after massaging a proprietary topical cream (Cyclo 3) containing melilot and butcher’s broom on her legs three times daily. On the first occasion her INR rose from about 2 to 5.8 after 7 days of use, and on a later occasion it rose to 4.6 after 10 days of use. In another report, a woman with unexplained abnormal menstrual bleeding was found to have a prothrombin time of 53 seconds, and laboratory tests showed that her blood clotting factors were abnormally low. When given parenteral vitamin K her prothrombin time rapidly returned to normal (suggesting that she was taking a vitamin K antagonist of some kind). She strongly denied taking any anticoagulant drugs, but it was eventually discovered that she had been drinking large quantities of a herbal tea containing among other ingredients tonka beans, melilot and sweet woodruff, all of which might contain natural coumarins.

Experimental evidence

No relevant data found.

Mechanism

Unknown. Melilot is known to contain natural coumarins, although these do not possess the minimum structural requirements required for anticoagulant activity. See Natural coumarins + Warfarin and related drugs). It seems that fermentation and spoilage of the melilot by mould are necessary for anticoagulant effects to occur.

Importance and management

Evidence appears to be limited to these isolated cases, which are not established. Many factors influence anticoagulant control, and therefore 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.