Co‐Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population‐Based Register Study

Rikala, Maria; Hauta-Aho, Milka; Helin‐Salmivaara, Arja; Lassila, Riitta; Korhonen, Maarit Jaana; Huupponen, Risto

doi:10.1111/bcpt.12373

Cited by 16 publications

(20 citation statements)

References 57 publications

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“…Finally, we did not adjust our analyses for concomitant use of CYP3A4 inhibitors or inducers. However, as reported previously, exposure to these medications was rare in our data (<0.5% of individuals in this cohort at warfarin initiation and ≤0.5% of total person‐time exposed to warfarin in 2010 ).…”

Section: Discussionsupporting

confidence: 71%

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Korhonen

Tiittanen

Kastarinen

et al. 2018

Basic Clin Pharma Tox

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Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

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Section: Discussionsupporting

confidence: 71%

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Korhonen

Tiittanen

Kastarinen

et al. 2018

Basic Clin Pharma Tox

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“…NSAIDs have been among the most common interacting drugs in inpatients and outpatients taking warfarin [3,4,9,27]. This trend seems to have changed and similar results to ours have been recently published in large register-based studies [11,28,29]. These findings may indicate increased awareness of clinicians of the increased bleeding risk associated with concomitant use of NSAIDs with warfarin.…”

Section: Discussionsupporting

confidence: 82%

“…More importantly, the excess risk caused by drug interactions is predictable and often avoidable by choosing alternative medications. Despite this, previous studies show that up to 60-80% of warfarin users, the majority of whom are older people, are exposed to potential drug interactions [9][10][11][12]. However, to our knowledge, there is no existing research on the frequency of warfarin drug interactions in frail patients compared to non-frail patients.…”

Section: Introductionmentioning

confidence: 98%

Frailty and Co-Prescribing of Potentially Interacting Drugs in New Users of Warfarin

et al. 2020

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Background Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known. Objective The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients. Methods We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation. Results In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively. Conclusions The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

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“…Numerous studies have shown that polypharmacy in elderly adults is related to adverse drug events and multiple coexisting impairments. 22) We found that polypharmacy was not solely a problem among elderly adults; polypharmacy was also common among younger adults taking warfarin. Warfarin is used for individuals with high-risk conditions such as AF or venous thromboembolism.…”

Section: Discussionmentioning

confidence: 77%

Adherence and Concomitant Medication Use among Patients on Warfarin Therapy: Insight from a Large Pharmacy Dispensing Database in Japan

Takeuchi

Nakano

Tanaka‐Mizuno

et al. 2019

Biological & Pharmaceutical Bulletin

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Warfarin is a drug used for anticoagulation management, with a narrow therapeutic range and multiple drug-drug interactions. Adherence and proper use of concomitant medication are thus fundamental to the efficacy and safety of warfarin therapy. In 2012, we retrospectively analyzed data from three large-scale pharmacy chains in Japan. We included all adults (≥ 20 years old) with at least one record of warfarin dispensation. We examined patient demographic data, adherence as measured by medication possession ratio (MPR), and co-dispensation focusing on the number of concomitant dispensations and concurrent use of medications that increase bleeding risk. Thresholds of underadherence and overadherence were set at <0.9 and >1.1, considering the narrow therapeutic window. We reviewed 443007 warfarin dispensation records of 71340 individuals (median age, 73 years; 62% male). The MPR was 1.0 (interquartile range: 0.96-1.0), and underadherence and overadherence was found in 16.3 and 1.9% of individuals, respectively. The median number of co-dispensed drugs was eight at each pharmacy encounter, which did not differ by age group. Drugs associated with a high bleeding risk were dispensed in 40.0% of encounters and accounted for 16.4% of all co-dispensed drugs. In summary, we found optimal overall adherence, as assessed by MPR, among our Japanese study population, even when defining a strict cutoff value. However, polypharmacy was common in all age groups and medications with a high bleeding risk profile were often co-dispensed with warfarin. Future research addressing how these dispensation patterns affect patient outcome is warranted.

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Co‐Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population‐Based Register Study

Cited by 16 publications

References 57 publications

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Statins do not Increase the Rate of Bleeding Among Warfarin Users

Frailty and Co-Prescribing of Potentially Interacting Drugs in New Users of Warfarin

Adherence and Concomitant Medication Use among Patients on Warfarin Therapy: Insight from a Large Pharmacy Dispensing Database in Japan

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