Clinically relevant drug interactions between newer antidepressants and oral anticoagulants

Spina, Edoardo; Cicala, Giuseppe; Bruno, Antonio; Leon, José de

doi:10.1080/17425255.2020.1700952

Cited by 33 publications

(29 citation statements)

References 96 publications

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“…Bleeding is a common complication of warfarin therapy and its hepatic metabolism and synergism are the most common underlying mechanisms for the occurrence of drug-drug interactions. The co-administration of these types of drugs requires great caution since it may result in serious ADRs, as it has been previously reported by other authors ( Blix et al, 2004 ; Mirosevic Skvrce et al, 2011 ; Spina et al, 2020 ). In patients starting therapy with warfarin, physicians should consider using an alternative medication with a more limited potential for interactions and provide recommendations for the timing of INR monitoring.…”

Section: Discussionmentioning

confidence: 79%

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database

et al. 2021

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Background: Drug-drug interactions (DDIs) are an important cause of adverse drug reactions (ADRs). In literature most of studies focus only on potential DDIs, while detailed data on serious ADRs associated with DDIs are limited. Our aim is to identify and characterize serious ADRs caused by DDIs using a spontaneous reporting database.Methods: All serious ADR reports, not related to vaccines and with a “definite”, “probable” or “possible” causality assessment, inserted into the National Pharmacovigilance database from Veneto Region (January 1, 2015 to May 31, 2020) were analyzed. A list of drug pairs was created by selecting the reports containing at least two suspected or concomitant drugs. We verified which drug pairs potentially interacted according to the online version of DRUGDEX® system. For each potential DDI we controlled whether the ADR description in the report corresponded to the interaction effect as described in Micromedex. A detailed characterization of all serious reports containing an occurring DDI was performed.Results: In the study period a total of 31,604 reports of suspected ADRs from the Veneto Region were identified, of which 2,195 serious reports (6.9% of all ADR reports) containing at least two suspected or concomitant drugs were analyzed. We identified 1,208 ADR reports with at least one potential DDI (55.0% of 2,195) and 381 reports (17.4% of 2,195 reports) with an occurring ADR associated with a DDI. The median age of patients and the number of contraindicated or major DDIs were significantly higher in reports with an occurring DDI. Warfarin was the most frequently reported interacting drug and the most common ADRs were gastrointestinal or cerebral hemorrhagic events. The proton pump inhibitors/warfarin, followed by platelet aggregation inhibitors/warfarin were the drug-drug combinations most frequently involved in ADRs caused by DDIs. The highest proportion of fatal reports was observed with platelet aggregation inhibitors/warfarin and antidepressants/warfarin.Conclusion: Our findings showed that about one-third of patients exposed to a potential DDI actually experienced a serious ADR. Furthermore, our study confirms that a spontaneous reporting database could be a valuable resource for identifying and characterizing ADRs caused by DDIs and the drugs leading to serious ADRs and deaths.

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Section: Discussionmentioning

confidence: 79%

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database

et al. 2021

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“…Previous studies have reported the association of antidepressant use with bleeding risk in OAC users. SSRI use has been associated with an increased risk of bleeding among OAC users in some studies [26,27], but not others [28][29][30]. The findings could potentially be explained by SSRIs' interference with hepatic cytochrome P-450 isoenzyme metabolic pathways, which are responsible for warfarin metabolism [31].…”

Section: Discussionmentioning

confidence: 99%

Association of Type of Antidepressant Initiation with Bleeding Risk in Atrial Fibrillation Patients Taking Oral Anticoagulants

Shao

Claxton

Lutsey

et al. 2021

Drugs - Real World Outcomes

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Background Inconsistent evidence suggests that use of certain antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), in patients using oral anticoagulants (OACs) might be associated with an elevated risk of bleeding. Objective This study aims to investigate the risk of bleeding associated with initiation of different types of antidepressants among atrial fibrillation (AF) patients on OAC therapy. Patients and methods A total of 30,336 AF patients (mean age 72.2 years; 54% female) on OAC therapy that started antidepressant treatment were identified from the Truven Health Analytics MarketScan Commercial and Medicare Databases for the period 2007-2015. Exposure was defined as filling a prescription for antidepressant, and categorized as SSRI, serotonin/ norepinephrine reuptake inhibitors (SNRIs), serotonin reuptake inhibitors (SRIs), tricyclic antidepressants (TCAs), or other antidepressants. The primary outcome was incident hospitalized bleeding. Associations of antidepressant type with bleeding were assessed calculating hazard ratios (HRs) and 95% confidence intervals (CIs) with adjusted Cox models in pairwise propensity score-matched cohorts. Results During a mean follow-up of 21 months, we identified 1612 bleeding episodes. In pairwise comparisons, SSRI use was associated with an increased risk of bleeding when compared to most other antidepressants (HR 1.22, 95% CI 0.96-1.54 vs SNRI; HR 1.10, 95% CI 0.90-1.35 vs SRI; HR 1.03, 95% CI 0.82-1.30 vs TCA). SNRI use was associated with the lowest bleeding risk. Results did not differ by OAC type, age, and sex. Conclusions Among AF patients on OAC initiating antidepressants, risk of bleeding varied across antidepressant type. This information can inform treatment choices among patients receiving OAC.

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“…Recently, Anderson et al [126] hypothesized that fluvoxamine might also exert beneficial effects in COVID patients through its well-characterized ability to substantially increase nighttime plasma levels of melatonin. Fluvoxamine and fluoxetine may substantially increase the bleeding risk associated with warfarin (a CYP2C9 substrate) through the inhibition of the CYP2C9mediated oxidative metabolism of the more biologically active (S)-enantiomer of warfarin, especially in elderly patients [127]. Also, SSRIs that inhibit CYP2C19, such as fluvoxamine and fluoxetine, can reduce the conversion of clopidogrel to its active metabolite, thereby reducing the concentration of the active antiplatelet agent in the blood [128].…”

Section: Drug-drug Interactionsmentioning

confidence: 99%

Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives?

Pashaei

2021

Journal of Clinical Neuroscience

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Clinically relevant drug interactions between newer antidepressants and oral anticoagulants

Cited by 33 publications

References 96 publications

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database

Identifying and Characterizing Serious Adverse Drug Reactions Associated With Drug-Drug Interactions in a Spontaneous Reporting Database

Association of Type of Antidepressant Initiation with Bleeding Risk in Atrial Fibrillation Patients Taking Oral Anticoagulants

Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives?

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