Quantity and quality of potential drug interactions with coumarin anticoagulants in the Netherlands

Abstract

Objective Coumarin anticoagulants are prone to potentially life-threatening drug-drug interactions due to a combination of unfavorable properties. However, real life data on the actual occurrence are scarce. The aim of this study was to quantify and qualify potential drug interactions with coumarin anticoagulants in daily practice. Methods A cohort study including all users of phenprocoumon or acenocoumarol during the period 1991-2003 in the PHARMO Record Linkage System. All 24 individual drugs and 11 drug groups interacting with coumarins according to central database used in the Dutch pharmacies were considered. Main outcome measure Frequency and type of potential drug interactions during anticoagulant therapy with coumarins. Results 48,627 out of 76,455 mainly acenocoumarol-users (64%) were dispensed at least one potentially interacting drug (PID) during anticoagulant therapy. About 35% of these cases were dispensed a (very) strongly interacting drug, whereas 3% were dispensed a contraindicated drug. Antibacterial drugs and NSAIDs (39% and 37% of all users, respectively) were the most frequently dispensed PIDs. Conclusion Potential drug interactions with coumarins frequently occur in daily practice, confronting two-thirds of patients with an increased risk of bleeding. To a large part, this is attributable to commonly prescribed medication like antibacterial drugs and NSAIDs. This situation substantiates the need for proper monitoring or new anticoagulants with less drug-drug interactions.

Identification and weighting of the most critical “real-life” drug–drug interactions with acenocoumarol in a tertiary care hospital

“…DDIs between NSAIDs, including COX-2 inhibitors, and oral anticoagulants are clearly documented in the literature and are frequently highlighted in studies on interactions and oral anticoagulants [12,41].…”

“…NSAIDs and antibacterial drugs were the most frequently interacting drugs. In this study, 24 individual drugs and 11 drug groups interacting with VKAs according to the central database used in Dutch pharmacies were taken into account [12]. The same authors, using the same methodology, but including new users of phenprocoumone or acenocoumarol, subsequently identified the main comedications associated with major bleeding episodes during anticoagulant therapy as antibacterial drugs, NSAIDs, antithrombotic drugs and tramadol [58].…”

“…tobacco, weight, sex, age and single nucleotide polymorphisms) influence the response to acenocoumarol treatment [5,11]. Drug-drug interactions (DDIs) are an additional factor affecting the variability of anticoagulation and the occurrence of serious ADRs [4,[12][13][14][15]. These DDIs are well described in the literature, but their respective importance in clinical practice is difficult to determine, especially those involving acenocoumarol since most of the studies published to date have focused on warfarin.…”

Warfarin‐associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

“…Observational studies indicate that antiplatelet and anticoagulant combinations, with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), selective serotonin re-uptake inhibitors (SSRIs) or antibacterial drugs increase bleeding risk [11,[13][14][15][16][17]. Up to 80% of anticoagulant users are described as using potentially hazardous combinations of medicines [18,19]. Studies of anticoagulant-related bleeding events from spontaneous reporting systems also show frequent use of interacting medicines, but the types of interacting medicines have not been described in detail [1,3].…”

Acompanhamento Farmacoterapêutico De Pacientes Em Uso De Varfarina: Uma Revisão Da Literatura

“…Além das interações com medicamentos, a atividade anticoagulante depende do consumo de determinados grupos de alimentos, com destaque aos ricos em vitamina K (PENNING- VAN et al, 2007;ELHATTON, 2009;ASSIS et al, 2012). Diante desses fatores de risco, Timi (1988) destaca que a varfarina tem sido vista como um desafio, justificado pela baixa adesão ao tratamento, agravado nos casos em que existe dificuldade geográfica de acesso ao local de atendimento.…”