Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

Galgani, Alessandro; Palleria, Caterina; Iannone, Luigi Francesco; Sarro, Giovambattista De; Giorgi, Filippo Sean; Maschio, Marta; Russo, Emilio

doi:10.3389/fneur.2018.01067

Cited by 64 publications

(54 citation statements)

References 76 publications

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“…A more complex issue concerns the new oral anticoagulants because their clinical effects cannot be easily monitored and several DDIs with ASMs may occur. 81 Noteworthy, in a recent guideline, the combination of some new anticoagulants not only with old‐generation EI‐ASMs but also with levetiracetam, oxcarbazepine, topiramate, and VPA has been contraindicated 82 …”

Section: Resultsmentioning

confidence: 99%

Drug treatments in patients with cardiac diseases and epilepsy

et al. 2020

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Objective: Comorbidity between epilepsy and heart diseases is frequent.Methods: All drugs classified within the group of drugs for cardiovascular system according to the Anatomical Therapeutic Chemical (ATC) classification system were reviewed for their effects on seizures or epilepsy. Results: Several agents showed antiseizure properties in animal models of seizures and/or in patients with epilepsy and only few were proconvulsant. Drugs with anticonvulsant effects include mecamylamine and guanfacine (antihypertensive drugs), indapamide, amiloride, furosemide and bumetanide (diuretics), fasudil (peripheral vasodilator), bioflavonoids (vasoprotective drug), propranolol (beta blocking agent), isradipine, nimodipine, verapamil and diltiazem (calcium channel blockers: CCBs), fosinopril and zofenopril (agents acting on the renin-angiotensin system), several statins, and fenofibrate (lipid-modifying agents). Drugs with proconvulsant properties in experimental models or in patients include reserpine, buflomedil, naftidrofuryl, and clonidine and propranolol at high doses. Drug-drug interactions (DDI) between antiseizure medications (ASMs) and drugs for cardiovascular system were also searched in two leading publicly accessible drug compendia. The most important DDIs occur between enzyme-inducing (EI) ASMs and ivabradine, ranolazine, macitenan and between EI-ASMs and the CCBs felodipine, nicardipine, nisoldipine, and verapamil. Simvastatin and atorvastatin are the lipid-modifying agents with more DDIs with EI-ASMs. Several pharmacodynamic interactions have been also documented. Discussion and conclusions: Available data show that the treatment of patients with epilepsy and vascular comorbidities is challenging and requires the appropriate knowledge of pharmacological properties of drugs and drug interactions. K E Y W O R D S antiepileptic drugs, antihypertensive drugs, antiseizure medications, comorbidity, diuretics, drug interactions, statins

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Section: Resultsmentioning

confidence: 99%

Drug treatments in patients with cardiac diseases and epilepsy

et al. 2020

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“…Rivaroxaban is not a pro-drug and has a rapid bioavailability [2]. Rivaroxaban is lipophilic and has a limited aqueous solubility, which can explain its increased bioavailability with a fed state for doses at 20 mg.…”

Section: Rivaroxaban's Absorption and Distributionmentioning

confidence: 99%

“…Dialysis is not expected to remove rivaroxaban [15] because of its binding to plasma proteins. Serum albumin is the most significant protein binding for rivaroxaban [2,5,9,15].…”

Section: Rivaroxaban's Absorption and Distributionmentioning

confidence: 99%

“…They could be co-administrated [2]. But again, the author states that an effect on CYP has not been shown but, since this AED may induce Pg-p activity, and is a substrate itself of this transporter, its safety in patients taking DOACs still needs to be demonstrated [2].…”

Section: Drugs Used In Neurologymentioning

confidence: 99%

“…Rivaroxaban belongs to the Direct Oral Anticoagulant (DOAC) group, also known as non-vitamin K oral anticoagulants (NOACs), which includes factor Xa inhibitors: Apixaban (Eliquis®), Edoxaban (Savaysa, Lixiana), and rivaroxaban (Xarelto), and direct thrombin inhibitors: Dabigatran (Pradaxa®) and argatroban [2]. Rivaroxaban (Xarelto; Bayer HealthCare) became the first direct inhibitor of factor Xa to be approved for clinical use in 2008 [3].…”

Section: Introductionmentioning

confidence: 99%

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Developing Deep Venous Thrombosis while on Rivaroxaban: A Review of Rivaroxaban

Al-Khafaji¹

2020

Clin Case Rep

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Rivaroxaban is a Direct Oral Anticoagulant (DOAC), which has six licensed indications, including the use for prevention of stroke and systemic embolism with non-valvular Atrial Fibrillation (AF) and the treatment of Venous Thromboembolism (VTE). The pharmacokinetics and the pharmacogenetics of rivaroxaban are reviewed by the author because of a previously reported case of a 43-year-old Caucasian female, who was diagnosed with popliteal and calf Deep Venous Thrombosis (DVT) while on anticoagulation treatment in the form of rivaroxaban 20 mg PO daily. This treatment was started because of a previously verified bilateral Pulmonary Embolism (PE) 5 months earlier. Rivaroxaban is more frequently used in clinical practice, and many physicians are aware that rivaroxaban requires adaptation mainly on the patient's renal function. However, there is still a need to increase awareness of rivaroxaban's interactions with drugs that share its pathways when the hepatic CYP450 and/or P-gp/BCRP are involved. These pathways are utilized by several medications, which are used in cardiovascular and neurological diseases, and the treatment of infections. These interactions can result in under or overexposure to rivaroxaban, which both effects can be detrimental. The author makes several cautious suggestions to decrease the incidence of under/overexposure of rivaroxaban. Physicians, including primary care physicians, could receive a clinical course focusing on DOACs for anticoagulation treatment or direct clinical training within a short-term Anticoagulation Team (ACT) stewardship program concerning adequate prescriptions of rivaroxaban/DOAC as well as their interactions. Also, patients who are elderly and/or with polypharmacy while taking rivaroxaban require more frequent controls. Furthermore, research exploring the effects of ABCG1, ABCG2, CYP3A4, CYP3A5, and Drug-Drug Interactions (DDI), is warranted. Finally, there is a need to identify a validated method for measuring rivaroxaban in primary care.

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Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding

Rahman,

Platt,

Beradid

et al. 2024

JAMA Netw Open

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ImportanceSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized.ObjectivesTo assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk.Design, Setting, and ParticipantsA population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration.ExposuresConcomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone.Main Outcomes and MeasuresThe main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding.ResultsThere were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47).Conclusions and RelevanceThis study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.

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Pharmacokinetic Interactions of Clinical Interest Between Direct Oral Anticoagulants and Antiepileptic Drugs

Cited by 64 publications

References 76 publications

Drug treatments in patients with cardiac diseases and epilepsy

Drug treatments in patients with cardiac diseases and epilepsy

Developing Deep Venous Thrombosis while on Rivaroxaban: A Review of Rivaroxaban

Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding

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