Fluvoxamine Interaction with Warfarin

Limke, Kristi K; Shelton, Angela R; Elliott, Ellie

doi:10.1345/1542-6270(2002)036<1890:fiww>2.0.co;2

Cited by 10 publications

(15 citation statements)

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“…As only eight cases were exposed to fluvoxamine and six to venlafaxine, the clinical significance of our results should be interpreted cautiously. However, our findings for fluvoxamine are supported by two case reports for INR increase during warfarin treatment [19,22]. In agreement with our results, clinical trials which focused on an interaction of fluoxetine, citalopram or sertraline with warfarin reported no or only very small increases in prothrombin time which were not regarded to be of clinical relevance [32,39,40].…”

Section: Tablesupporting

confidence: 92%

Selective serotonin re‐uptake inhibiting antidepressants and the risk of overanticoagulation during acenocoumarol maintenance treatment

Teichert

Visser

Uitterlinden

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Coumarin anticoagulants and selective serotonin re-uptake inhibitors (SSRIs) have been reported to cause bleeding. Combination of these drug groups might enhance this risk. Case reports showed an increase of prothrombin time for the combination of warfarin with fluvoxamine and fluoxetine. This has not yet been confirmed by population based studies. WHAT THIS STUDY ADDS• Fluvoxamine and venlafaxine increased prothrombin time in users of acenocoumarol above a critical value which is associated with an increased bleeding risk.The other SSRIs had no influence on acenocoumarol effectiveness, however numbers of drug users were low.The combination of fluvoxamine and venlafaxine with acenocoumarol should be monitored by measurements of the international normalized ratio to avoid overanticoagulation. AIMThe aim of this study was to investigate the effects of co-medication with selective serotonin re-uptake inhibitors (SSRIs) on overanticoagulation during acenocoumarol maintenance treatment. METHODSAll subjects from The Rotterdam Study who received acenocoumarol maintenance treatment between April 1 1991 and September 9 2009 were followed for the event of an international normalized ratio (INR) Ն6, until death, end of treatment or end of the study period. With the Andersen-Gill extension of the Cox proportional hazards model, risks for repeated events of overanticoagulation in relation to concomitant SSRI use were calculated. RESULTSThe risk for overanticoagulation during acenocoumarol maintenance treatment was increased in combination with fluvoxamine (HR 2.63, 95% CI 1.49, 4.66) and venlafaxine (HR 2.19, 95% CI 1.21, 3.99). There was no increase in risk for the other SSRIs, but numbers of exposed cases were low for all SSRIs except paroxetine. CONCLUSIONFluvoxamine and venlafaxine were associated with a more than double risk of INR values Ն6 in acenocoumarol treated subjects.

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Section: Tablesupporting

confidence: 92%

Selective serotonin re‐uptake inhibiting antidepressants and the risk of overanticoagulation during acenocoumarol maintenance treatment

Teichert

Visser

Uitterlinden

et al. 2011

Brit J Clinical Pharma

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“…[8][9][10][11] This has been reported for upper GI bleedings as well as for the risk of cerebral haemorrhage. Second, bleeding events in patients with SSRI or other antidepressant therapy who received a coprescription with NOAC were higher than those recorded for co-medication with VKA.…”

Section: Resultsmentioning

confidence: 99%

“…An increased bleeding risk has been described for patients treated with SSRI and VKA compared with patients receiving other antidepressants in previous case reports and studies. [8][9][10][11] This has been reported for upper GI bleedings as well as for the risk of cerebral haemorrhage. 4,11,12 A drug-drug interaction may cause an increased bleeding risk, when anticoagulant and antidepressant medications are combined.…”

Section: Discussionmentioning

confidence: 99%

SSRI co‐medication with NOAC or VKA does not increase hospitalisation for bleeding: A retrospective nationwide cohort study in Austria 2010‐2015

Sheikh

Mittlböck

Reichardt

et al. 2019

Int J Geriat Psychiatry

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Objectives Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are used for the prophylaxis and treatment of thromboembolic events. A potential drug–drug interaction and increased bleeding events have been reported with co‐medication of selective serotonin receptor inhibitors (SSRIs) and VKA. The aim of this study was to investigate the bleeding risk of a coprescription of NOAC or VKA with SSRI. Methods Patients with prescription of NOAC or VKA and an antidepressant drug therapy (ADTx) were selected from the drug reimbursement database of 13 Austrian health insurance funds. For this cohort, hospital discharge diagnoses for gastrointestinal bleeding, cerebral haemorrhage, and bleeding anaemia between 2010 and 2015 were analysed. Results Data were available from 50 196 female and 31 308 male patients. Among these, 892 patients had 987 hospitalisations with bleeding events. The most frequent bleeding cases were gastrointestinal bleedings with 588 events (59.6%), followed by cerebral haemorrhage with 344 (34.8%), and bleeding anaemia with 55 events (5.6%), respectively. The risk of bleeding events was similar between SSRI and other ADTx, when combined with oral anticoagulants (p = 0.51). Concomitant treatment of patients with SSRI or other ADTx and NOAC was associated with an increased bleeding risk compared with cotreatment with VKA (1.21, 95% CI: 1.05‐1.40; p = 0.0097). Conclusion Co‐medication of SSRI with VKA or NOAC has little if any impact on hospital discharge diagnoses for bleeding events compared with cotreatment of those anticoagulants with other antidepressant medications.

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“…Oral anticoagulants. Case reports and literature reviews have suggested that SSRIs, in particular fluvoxamine and fluoxetine, may interact with the oral anticoagulant warfarin to cause bleeding (Woolfrey et al, 1993;Dent and Orrock, 1997;Duncan et al, 1998;Yap and Low, 1999;Sayal et al, 2000;Limke et al, 2002). SSRIs may increase the risk of hemorrhage during warfarin treatment by two mechanisms: first, SSRIs may reduce platelet aggregation by depleting platelet serotonin levels, directly increasing the risk of bleeding, as already mentioned (Dalton et al, 2006), and second, some SSRIs, particularly fluvoxamine and fluoxetine, may inhibit the CYP2C9-mediated oxidative metabolism of the more biologically active (S)-enantiomer of warfarin (Duncan et al, 1998;Sayal et al, 2000).…”

Section: Cardiovascular Drugsmentioning

confidence: 99%