380 Lettres à la rédaction

of concomitantly administered drugs (enalapril 20mg, furose-

Garlic Interaction mide 40mg, pravastatin 20mg) were unmodified. In November
with Fluindione: 2000, his INR suddenly dropped below its normal range (2.5) and
stayed below 2 for 12 consecutive days, despite an increase in
A Case Report the OAC dosage. The patient had not altered any of his habits,
and no factor known to decrease the effectiveness of OACs could
Interaction entre ail et fluindione be identified. The only change was an intake of garlic tablets (600
mg/day) for the previous 12 days. This patient told us that he was
Atul Pathak,1 Philippe Léger,2 Haleh taking garlic to improve his quality of life. Cessation of the garlic
Bagheri,1 Jean-Michel Senard,1 Henri intake normalised the INR within 4 days (table I). According to
Boccalon2 and Jean-Louis Montastruc1 the French method of causality assessment,[4] the imputability
was evaluated as ‘possible’ (C2S2).
1 Service de Pharmacologie Clinique, Centre
Midi-Pyrénées de Pharmacovigilance, de
Pharmacoépidémiologie et d’Informations sur le Discussion
Médicament, CHU de Toulouse, Toulouse, France
2 Service de Médecine Vasculaire, CHU de Toulouse, Despite the widespread use of dietary supplements in the US
Faculté de Médecine, Toulouse, France and Europe, no case reports of an interaction between garlic (A.
sativum) and fluindione have been identified.[5] The use of garlic
Texte reçu le 5 novembre 2002 ; accepté le 6 mars 2003 has been associated with decreased platelet aggregation and pro-
Cas déclaré au CRPV de Toulouse, le 6 décembre 2000 longed bleeding episodes.[2] However, the ability of garlic to de-
Keywords: garlic, fluindione, drug interaction crease the effectiveness of OACs has never been reported.
Mots clés : ail, fluindione, interaction médicamenteuse
This case report describes abnormal INR values in a patient
receiving fluindione. The fact that assays were always performed
Introduction
in the same laboratory enabled us to ascertain that the abnormal
Potential and documented interactions between alternative values were significantly different from the other values.
therapeutic agents (i.e. herbs and plants) and conventional drugs Changes in the anticoagulant activity of fluindione could be
have been described. Garlic (Allium sativum) is believed to pro- due to an interaction between the anticoagulant drugs and the
vide several cardiovascular benefits, such as a decrease in blood recently prescribed garlic. The chronology of the appearance and
pressure or plasma lipid levels[1] as well as having antioxidant disappearance of the biological alteration (i.e. INR modifica-
properties. However, a major safety concern remains regarding tions) suggests that this effect can be imputed to garlic.
an interaction with drugs with a narrow therapeutic index, such The mechanism of such an interaction could be located at
as oral anticoagulants (OACs). different levels of the fluindione pharmacokinetics. Since it is
The effect of garlic on OACs mainly results in increased known that garlic is able to inhibit some cytochrome P450
bleeding, which is partly mediated by garlic-induced platelet dys- isoforms,[6] this agent could putatively increase fluindione meta-
function.[2] Although in vitro studies have provided some evi- bolism, thereby acting as an enzymatic inducer. Another mecha-
dence for this effect, clinical studies have not confirmed this ob-
servation.[2] Most of the available information relates to studies Table I. Evolution of the patient’s international normalised ratio (INR)
with warfarin and less is known about a garlic interaction with Date INR Mean dose of
fluindione (mg)
fluindione.[3]
October 23, 2000 (without garlic) 2.4 5.0
November 8, 2000 (with garlic) 1.5 6.6
Case Report November 9, 2000 (with garlic) 1.7 6.6
November 13, 2000 (with garlic) 1.2 10.0
The current report describes an interaction between garlic
November 20, 2000 (after 12 days 1.8 10.0
and fluindione in an 82-year old man. He received fluindione in with garlic)
November 1999 to prevent cardioembolic complications associ- November 27, 2000 ( 7 days after 2.8 6.6
ated with chronic atrial fibrillation. Past medical history in- stopping garlic)
cluded arterial hypertension, and hypercholesterolaemia. December 14, 2000 2.5 6.6
From November 1999 to November 2000, the patient’s inter- January 23, 2001 2.5 6.6
national normalised ratio (INR) was between 2 and 3. Dosages February 13, 2001 2.3 6.6

 2003 Société Française de Pharmacologie Thérapie 2003 Juil-Août; 58 (4)

Lettres à la rédaction 381

nism could be inhibition of fluindione binding to plasma proteins.

However, there are no reports in the literature of such properties Intoxication à la
for garlic.
This case report reinforces information about an interaction
propafénone
with fluindione, which remains scarce in the available literature. Propafenone Poisoning
Because of the continuing growth in the use of dietary supple-
ments, there is a concern regarding the potential for particularly Nouredine Sadeg,1 Jacques Richecoeur2
acute and life-threatening interactions with allopathic drugs such et Michel Dumontet1
as fluindione. When patients treated with fluindione start or dis-
continue dietary supplements, it would be advisable to monitor 1 Laboratoire Claude Bernard, Centre Hospitalier
René Dubos, Pontoise, France
INR and bleeding time. Although dietary supplements are not
2 Unité Réanimation Médicale, Centre Hospitalier
considered as drugs with official labelling, they are not innocuous René Dubos, Pontoise, France
and may have the potential to affect the efficacy and safety of
concurrently administered drugs. The true risk of these effects Texte reçu le 22 mars 2002 ; accepté le 1er avril 2003
may be difficult to characterise because of the limited number Cas notifié le 29 octobre 2001 au Centre de Pharmacovigilance
and nature of existing reports. des Laboratoires KNOLL, France

Mots clés : propafénone, intoxication, antiarythmique,

References charbon activé
1. Fugh-Berman A. Herbs and dietary supplements in the prevention and treatment
of cardiovascular disease. Prev Cardiol 2000; 3: 24-32 Keywords: propafenone, poisoning, antiarrhythmic agent,
2. Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis charcoal
1978; 30: 355-60
3. Vaes LPJ, Chyka PA. Interactions of warfarin with garlic, ginger, ginkgo, or gin-
seng: nature of the evidence. Ann Pharmacother 2000; 34: 1478-82
4. Begaud B, Evreux JC, Jouglard J, et al. Imputabilité des effets inattendus ou
toxiques des médicaments : actualisation de la méthode utilisée en France.
Introduction
Thérapie 1985; 40: 111-8
La propafénone est un antiarythmique appartenant à la classe
5. Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355: 134-8
6. Zou L, Harkey MR, Henderson GL. Effects of herbal components on cDNA- Ic de la classification de Vaughan Williams ; il est actif sur les
expressed cytochrome P450 enzyme catalytic activity. Life Sci 2002; 71: troubles du rythme auriculaire, jonctionnel et ventriculaire.[1]
1579-89
Nous rapportons le cas d’un enfant ayant fait une tentative
d’autolyse avec du propafénone (Rythmol®) et ayant développé
Correspondence and offprints: Atul Pathak, Service de Pharmacologie
un tableau clinique gravissime constitué de troubles cardio-
Clinique, Centre Midi-Pyrénées de Pharmacovigilance, 37 allée Jules respiratoires, neurologiques et crises convulsives avec coma.
Guesde, B.P. 7202, 31073 Toulouse Cedex 7, France. Nous avons essayé dans ce manuscrit de démontrer l’intérêt
E-mail: pathak@cict.fr
d’une administration réitérée du charbon activé dans l’arsenal
thérapeutique pour espérer une issue favorable lors d’une into-
xication à la propafénone.

Observation
Un enfant, âgé de 13 ans, est admis aux urgences pour ten-
tative de suicide par la propafénone. La quantité de propafénone
supposée ingérée par l’enfant est de 3 g.
Le patient présente une convulsion avec bradycardie
extrême, une cyanose et une hypotension ; le pouls est imprenable
conduisant à un arrêt cardiorespiratoire. Nous avons mis en
route une réanimation symptomatique associant un massage car-
diaque externe, une intubation et une perfusion d’amines vaso-
pressives et inotropes (adrénaline et dobutamine) avec du lactate
de sodium molaire. Une récupération hémodynamique satis-
faisante est notée avec pouls bien frappé, après 45 minutes. Nous

 2003 Société Française de Pharmacologie Thérapie 2003 Juil-Août; 58 (4)