Revisiting the Significance of Warfarin Protein-Binding Displacement Interactions

Sands, Charles D.; Chan, Edwina S; Welty, Timothy E.

doi:10.1345/aph.1a208

Cited by 19 publications

(6 citation statements)

References 25 publications

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“…These are mainly for drugs without much first-pass liver metabolism. The principal plasma proteins for drug binding are[11]:…”

Section: Mechanismsmentioning

confidence: 99%

Drug Interaction and Pharmacist

Ansari

2010

Journal of Young Pharmacists

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The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy.

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“…These are mainly for drugs without much first-pass liver metabolism. The principal plasma proteins for drug binding are[11]:…”

Section: Mechanismsmentioning

confidence: 99%

Drug Interaction and Pharmacist

Ansari

2010

Journal of Young Pharmacists

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“…The second mechanism involves displacement of highly protein-bound drugs such as warfarin (~99% protein-bound), with the addition of other highly protein-bound drugs such as tizoxanide resulting in the displacement of warfarin, an increase in the unbound (free) fraction, and an increase in pharmacodynamic response. 18 , 42 , 43 However, these effects are likely to be short-lived and of limited clinical significance since the metabolism of the displaced drug usually increases, which offsets the increase in the unbound drug fraction. 18 , 42 …”

Section: Drug–drug Interactionsmentioning

confidence: 99%

“… 18 , 42 , 43 However, these effects are likely to be short-lived and of limited clinical significance since the metabolism of the displaced drug usually increases, which offsets the increase in the unbound drug fraction. 18 , 42 …”

Section: Drug–drug Interactionsmentioning

confidence: 99%

Drug–Drug–Gene Interactions in Cardiovascular Medicine

Asiimwe¹,

Pirmohamed²

2022

PGPM

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Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug–drug interactions, DDIs) and genomic factors (drug–gene interactions, DGIs) can influence cardiovascular drug-related efficacy and safety outcomes. Although thousands of DDI and DGI (aka pharmacogenomic) studies have been published to date, the literature on drug–drug–gene interactions (DDGIs, cumulative effects of DDIs and DGIs) remains scarce. Moreover, multimorbidity is common in cardiovascular disease patients and is often associated with polypharmacy, which increases the likelihood of clinically relevant drug-related interactions. These, in turn, can lead to reduced drug efficacy, medication-related harm (adverse drug reactions, longer hospitalizations, mortality) and increased healthcare costs. To examine the extent to which DDGIs and other interactions influence efficacy and safety outcomes in the field of cardiovascular medicine, we review current evidence in the field. We describe the different categories of DDIs and DGIs before illustrating how these two interact to produce DDGIs and other complex interactions. We provide examples of studies that have reported the prevalence of clinically relevant interactions and the most implicated cardiovascular medicines before outlining the challenges associated with dealing with these interactions in clinical practice. Finally, we provide recommendations on how to manage the challenges including but not limited to expanding the scope of drug information compendia, interaction databases and clinical implementation guidelines (to include clinically relevant DDGIs and other complex interactions) and work towards their harmonization; better use of electronic decision support tools; using big data and novel computational techniques; using clinically relevant endpoints, preemptive genotyping; ensuring ethnic diversity; and upskilling of clinicians in pharmacogenomics and personalized medicine.

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“…The pharmacodynamic activity of warfarin is strongly related to the fractions of free (unbound) drug. Therefore drugs that alter the plasma protein binding of warfarin, including valproic acid and non-steroidal anti-inflammatory drugs (NSAIDs), can potentiate the anticoagulant effects of warfarin 22. In addition, drugs such as NSAIDs that possess antiplatelet activity can produce additive anticoagulant effects on concurrent administration with warfarin 23…”

Section: Introductionmentioning

confidence: 99%

Comparative evaluation of warfarin utilisation in two primary healthcare clinics in the Cape Town area : cardiovascular topics

Njovane

Fasinu

Rosenkranz

2013

CVJA

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BackgroundAlthough warfarin remains the anticoagulant drug of choice in a wide range of patients, its narrow therapeutic window makes patients susceptible to a high risk of bleeding complications or failure to prevent clotting. This has necessitated therapeutic monitoring in warfarinised patients. Factors that could be responsible for the fluctuating responses to warfarin vary from pharmacogenetic to concomitant morbidity, diet and medication. In order to assess the quality of management of warfarin treatment in a local primary-care setting, the current study evaluated warfarin utilisation and monitoring records in two hospitals with different patient groups.MethodsA retrospective study was undertaken in the specialised warfarin clinics at Wesfleur and Gugulethu hospitals (Western Cape, South Africa) covering all warfarin-related therapy records over a 12-month period. Data extracted from the patients’ folders included age, gender, race, weight, address, concurrent chronic illnesses, treatment and medication, indication for warfarin and INR history.ResultsA total of 119 patients’ folders were analysed. Attendance at the clinics reflects the demographics and racial distribution of the host location of the hospitals. While all the patients were maintained above the minimum international normalised ratio (INR) value of 2, about 50% had at least one record of INR above the cut-off value of 3.5. However, over a third of the patients (32.2%) had at least one record of INR greater than 3.5 in Gugulethu Hospital, compared to over half (58.3%) in Wesfleur Hospital.In total, atrial fibrillation was the most common indication for warfarinisation while hypertension was the most common concurrent chronic condition in warfarinised patients. All patients who received quinolone antibiotics had INR values above the cut-off point of 3.5 within the same month of the initiation of antibiotic therapy, suggesting drug-induced warfarin potentiation. Other co-medications, including beta-lactam antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and anti-ulcer drugs appeare to alter warfarin responses as measured by recorded INR values.ConclusionThe study found inter-individual variability in the response to warfarin therapy, which cut across racial classifications. It also confirms the possible influence of concomitant morbidity on patient response to anticoagulant therapy.

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Revisiting the Significance of Warfarin Protein-Binding Displacement Interactions

Cited by 19 publications

References 25 publications

Drug Interaction and Pharmacist

Drug Interaction and Pharmacist

Drug–Drug–Gene Interactions in Cardiovascular Medicine

Comparative evaluation of warfarin utilisation in two primary healthcare clinics in the Cape Town area : cardiovascular topics

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