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KOOPERATION PHYTOPHARMAKA GbR
Interaction between warfarin and Matricaria chamomilla?
In a case report (Segal and Pilote 2006) a 70-year old woman was hospitalized because of three relative large internal haematomas and a consecutive anaemia. She had a long-term mechanical mitral wave replacement and multiple medications: warfarin (known dose), amiodarone, digoxin, a betablocker, synthroid and others (dosages not given). The patient had a productive bronchitis for several days, since 5 days she was dyspnoeic on exertion and had bilateral pedal oedema. The International Normalized Ratio (INR) was 7.9 (5 days before it had been 3.6). After reduction of warfarin and conventional therapy the bleeding could be stopped.
Further questioning revealed medication with a chamomile-based skin lotion (one teaspoon 4-5 x per day, no further details) for the pedal oedema. Furthermore, she took 4-5 cups of tea per day each made from 1 teaspoon of dried chamomile leaves (no further details) for her sore throat. Both these preparations had already been used before on an regular basis. Dyspnoea was treated with a camphor-containing lotion. The authors attach the increase of INR to an interaction between warfarin and the chamomile lotion and tea, respectively.
The timely relationship between the use of chamomile preparation and the increase of INR
permits - from a formal perspective - an assessment as “possible” and “serious” because of
hospitalisation. The conclusions from this complex context drawn by the authors, however,
are questionable. There do exist further possibilities for explanation which the authors do not
discuss. Clinical aspects:
1. The application (from 1-2 to 4-5 times per day) of a chamomile-based skin lotion
presumably was not responsible for the haematomas.The pharmacodynamic interaction as
postulatred by the authors can be excluded. Minimal structure requirement for the
anticoagulant activity is a 4-hydroxycoumarin which has a nonpolar carbon substituent at the
3 position (e.g. -CH3). Chamomile coumarins (herniarin, umbelliferon), however, are 7-
hydroxy or –methoxy-coumarins, respectively, without substituent at the 3 position.
2. Amiodarone can induce SIADH (syndrome of inadequate ADH secretion). This syndrome
is characterized by hyperhydration which can hardly be influenced. SIADH sometimes is also
observed during more severe pulmonary infections. The decrease of creatinine from 97 to 82
mmol/L within 5 days and the lack of a reactive thrombocytosis after the large drop of
haemoglobin from 117 to 80 g/L may be hints to the existence of a SIADH.
3. Although the nursing daughter denies a change in diet intake, usually a reduced health
status (such as infection, oedema) is accompanied by a decreased quantity of diet intake. This
can enforce the effect of warfarin.
4. Bilateral pedal oedema and exertional dyspnoea may be hints to a progredient failure of the
(right) heart. One consequence is hepatic oedema which can result in a reduced synthesis of
the prothrombin complex and thereby lead to a reduction of spontaneous coagulability.
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In the Canadian publication 4-5 tea spoons of dried chamomile leaves
per day are applied as a
tea against sore throat. Important information on the species is lacking, thus it remains unclear
whether the officinal herbal drug Matricaria recutica (German chamomile) was used. At least
the leaves and not the flowers required by the Pharmacopoeia were used. Thus a transferral of
this case to preparations which correspond to the Pharmacopeia is not permitted. Interactions:
4-5 cups of chamomile tea are a standard daily dose (recommendation of Commission E: 3-4
cups several times a day in inflammations of the mouth and throat mucosa), which never
before has been described to cause bleeding complications.
The authors are of the opinion that a pharmacokinetic interaction cannot be ruled out,
however, they do not believe this was clinically significant in this particular case. In this
context the authors exclude an interaction mediated by inhibition of CYP isoenzymes. The
interaction between amiodarone and warfarin, digoxin and also betablockers by inhibition of
CYP 3A4 which increases the risk of bleeding and the anticoagulative effect of warfarin is
well-known and included in the package leaflets.
Due to multiple therapy the pharmacokinetic and pharmacodynamic context is very complex.
A causal relationship with one of the mentioned products can therefore not be concluded. In
particular, an anticoagulant effect of chamomile coumarins can be excluded due to their
structure. In any case a transferral of this case to preparations corresponding to
pharmacopoeias is not permitted.
Ganzera M, Schneider P, Stuppner H. Inhibitory effects of the essential oil chamomile (Matricaria recutita) L.) and its major constituents on human cytochrome P450 enzymes. Life Sci. 2006, 78:856-61
Majerus, PW, Tollefsen, DM. Oral anticoagulants. In: Hardman JG, Limbird LE, eds. Goodman & Gilman`s. The pharmacological basis of therapeutics. Tenth ed. New York: McGraw-Hill, 2001; 1526-1531
Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla. CMAJ 2006: 174; 1281-1282.
O Objective: To investigate the threshold of transcutaneous oxygen tension (TcPO ) values in predicting ulcer healing in patients with critical limb ischaemia in a prospective study. O Method: 50 patients suffering from critical limb ischaemia with chronic ischemic ulcers or gangrenous toes were enrolled in this study between January and December 2008. Their demographic data and ankle brac
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