W

Warfarin

Aceclofenac [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anti-coagulants, such as warfarin

Acenocoumarol, warfarin ---> SmPC of [econazole] of

Patients taking oral anticoagulants, such as warfarin or acenocoumarol, caution should be exercised and the anticoagulant effect should be monitored more frequently.

Acetylsalicylic acid, warfarin

Salicylates may enhance the anticoagulant effect with risk of bleeding

Afamelanotide [1], warfarin ---> SmPC of [1] of EMA

Patients taking substances which reduce coagulation, acetylsalicylic acid and non-steroidal anti-inflammatory drug (NSAIDs) may experience increased bruising or bleeding at the site of implantation.

Albiglutide [1], warfarin ---> SmPC of [1] of EMA

Albiglutide did not significantly alter the pharmacodynamic effects of warfarin as measured by the international normalized ratio (INR). In addition, albiglutide did not significantly alter the pharmacodynamic effects of warfarin as measured by the INR.

Alcohol, warfarin [2] ---> SmPC of [2] of eMC

Acute ingestion of a large amount of alcohol may inhibit the metabolism of warfarin and increase INR. Conversely, chronic heavy alcohol intake may induce the metabolism of warfarin. Moderate alcohol intake can be permitted.

Aliskiren, warfarin ---> SmPC of [aliskiren/amlodipine] of EMA

The effects of aliskiren on warfarin pharmacokinetics have not been evaluated.

Aliskiren/amlodipine [1], warfarin ---> SmPC of [1] of EMA

The effects of aliskiren on warfarin pharmacokinetics have not been evaluated.

Aliskiren/amlodipine/hydrochlorothiazide [1], warfarin ---> SmPC of [1] of EMA

The effects of aliskiren on warfarin pharmacokinetics have not been evaluated.

Aliskiren/hydrochlorothiazide [1], warfarin ---> SmPC of [1] of EMA

The effects of aliskiren on warfarin pharmacokinetics have not been evaluated.

Allopurinol, warfarin [2] ---> SmPC of [2] of eMC

Allopurinol potentiates the effect of warfarin

Alogliptin [1], warfarin ---> SmPC of [1] of EMA

In healthy subjects, alogliptin had no effect on prothrombin time or International Normalised Ratio (INR) when administered concomitantly with warfarin.

Alprazolam, warfarin

It could not be determined if there was any effect on the prothrombin time and the warfarin plasma concentrations

Alteplase, warfarin [2] ---> SmPC of [2] of eMC

Fibrinolytic drugs such as streptokinase and alteplase are contraindicated in patients receiving warfarin.

Ambrisentan [1], warfarin ---> SmPC of [1] of EMA

Ambrisentan had no effects on the steady-state pharmacokinetics and anti-coagulant activity of warfarin in a healthy volunteer study. Warfarin also had no clinically significant effects on the pharmacokinetics of ambrisentan.

Aminoglutethimide, warfarin

The enzymatic inductor may increase the metabolism of warfarin and decrease its plasma levels and the anticoagulant effect

Aminosalicyclic acid, warfarin

The co-administration may enhance the anticoagulant effect

Amiodarone [1], warfarin ---> SmPC of [1] of eMC

Amiodarone, CYP2C9 inhibitor, may increase the plasma concentrations and the risk of bleeding of warfarin

Amlodipine/valsartan [1], warfarin ---> SmPC of [1] of EMA

In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin or ciclosporin.

Amobarbital, warfarin [2] ---> SmPC of [2] of eMC

Barbiturates antagonise the effect of warfarin

Amoxicillin, warfarin ---> SmPC of [amoxicillin/clavulanic acid] of eMC

In the literature there are cases of increased international normalised ratio in patients maintained on warfarin and prescribed a course of amoxicillin.

Amoxicillin/clavulanic acid [1], warfarin ---> SmPC of [1] of eMC

In the literature there are cases of increased international normalised ratio in patients maintained on warfarin and prescribed a course of amoxicillin.

Amprenavir [1], warfarin ---> SmPC of [1] of EMA

A reinforced monitoring of the International Normalised Ratio is recommended in case of administration of Amprenavir with warfarin or other oral anticoagulants, due to a possible decrease or increase of their antithrombotic effect

Anagrelide [1], warfarin ---> SmPC of [1] of EMA

In vivo interaction studies in humans have demonstrated that digoxin and warfarin do not affect the pharmacokinetic properties of anagrelide.

Anakinra [1], warfarin ---> SmPC of [1] of EMA

It may be expected that for an IL-1 receptor antagonist, such as anakinra, the formation of CYP450 enzymes could be normalized during treatment. This would be clinically relevant for CYP450 substrates with a narrow therapeutic index (e.g. warfarin and phenytoin).

Antibiotics, warfarin ---> SmPC of [imipenem/cilastatin] of eMC

There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents.

Antiestrogens [1], warfarin ---> SmPC of [1] of EMA

There is a known interaction between anti-estrogens and warfarin-type anticoagulants leading to a seriously increased bleeding time. Therefore, the concomitant use of toremifene with such drugs should be avoided.

Apixaban [1], warfarin ---> SmPC of [1] of EMA

Due to an increased bleeding risk, concomitant treatment of apixaban with any other anticoagulants is contraindicated

Aprepitant [1], warfarin ---> SmPC of [1] of EMA

As a mild inducer of CYP2C9, CYP3A4 and glucuronidation, aprepitant can decrease plasma concentrations of substrates eliminated by these routes within 2 weeks following initiation and treatment.

Aripiprazole [1], warfarin ---> SmPC of [1] of EMA

When aripiprazole was administered concomitantly with warfarin, there was no clinically important change in concentrations of warfarin. Thus, no dosage adjustment is required

Ascorbic acid, warfarin

Vitamin C in high doses can decrease the anticoagulant effect

Atazanavir [1], warfarin ---> SmPC of [1] of EMA

Possible increased or decreased of the INR. It is recommended that the INR be monitored carefully during treatment

Atazanavir/cobicistat [1], warfarin ---> SmPC of [1] of EMA

Co-administration with EVOTAZ has the potential to increase warfarin plasma concentrations. The mechanism of interaction is CYP3A4 inhibition by atazanavir and cobicistat. It is recommended that the INR be monitored.

Atorvastatin [1], warfarin ---> SmPC of [1] of eMC

Prothrombin time should be determined before starting atorvastatin in patients taking coumarin anticoagulants and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs.

Atovaquone/proguanil [1], warfarin ---> SmPC of [1] of eMC

Proguanil may potentiate the effect of warfarin and other coumarin based anticoagulants which may lead to an increase in the risk of haemorrhage.

Azathioprine [1], warfarin ---> SmPC of [1] of eMC

Inhibition of the anticoagulant effect of warfarin and acenocoumarol has been reported when co-administered with azathioprine. Coagulation tests should be closely monitored when anticoagulants are coadministered with azathioprine.

Azilsartan medoxomil [1], warfarin ---> SmPC of [1] of EMA

No clinically significant interactions have been reported in studies of azilsartan medoxomil or azilsartan given with amlodipine, antacids, chlortalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin, and warfarin.

Azithromycin [1], warfarin ---> SmPC of [1] of eMC

Potentiation of the anticoagulant effect. Careful monitor the prothrombin time

Azole antifungals, warfarin [2] ---> SmPC of [2] of eMC

Azole antifungals potentiate the effect of warfarin

Barbiturates, warfarin [2] ---> SmPC of [2] of eMC

Barbiturates antagonise the effect of warfarin

Bazedoxifene, warfarin ---> SmPC of [conjugated oestrogens/bazedoxifene] of EMA

Based on in vitro bazedoxifene plasma protein-binding characteristics, interactions with warfarin, digoxin or diazepam are unlikely.

Benzbromarone, warfarin

Benzbromarone may enhance the effect and/or toxicity of warfarin

Benziodarone, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Beta interferon, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Beta-lactam antibiotics, warfarin ---> SmPC of [imipenem/cilastatin] of eMC

There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents.

Bicalutamide [1], warfarin ---> SmPC of [1] of eMC

Bicalutamide can displace the coumarin anticoagulant, warfarin, from its protein binding site. It is recommended that prothrombin time is closely monitored if bicalutamide is started in patients who are already receiving coumarin anticoagulants.

Bivalirudin [1], warfarin ---> SmPC of [1] of EMA

Combined use of anti-coagulant medicinal products can be expected to increase the risk of bleeding.

Blinatumomab [1], warfarin ---> SmPC of [1] of EMA

Patients who are receiving medicinal products that are CYP450 and transporter substrates with a narrow therapeutic index should be monitored for adverse effects (e.g. warfarin) or drug concentrations (e.g. cyclosporine) during this time.

Bosentan [1], warfarin ---> SmPC of [1] of EMA

Decreased plasma concentrations of warfarin

Breast-feeding, warfarin [2] ---> SmPC of [2] of eMC

Warfarin is excreted in breast milk in small amounts. However, at therapeutic doses of warfarin no effects on the breast-feeding child are anticipated. Warfarin can be used during breast-feeding.

Brexpiprazole [1], warfarin ---> SmPC of [1] of EMA

Based on results of in vitro studies brexpiprazole protein binding is not affected by warfarin, diazepam, and digitoxin.

Buspirone, warfarin

Reports of increased prothrombin time have been received in patients treated with buspirone and warfarin

Butabarbital, warfarin

The co-administration may decrease the anticoagulant effect

Capecitabine [1], warfarin ---> SmPC of [1] of EMA

Altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin and phenprocoumon.

Carbamazepine, warfarin [2] ---> SmPC of [2] of eMC

Carbamazepine antagonises the effect of warfarin

Carnitine, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Cefazolin, warfarin

Cefazolin may enhance the anticoagulant effect

Ceftriaxone, warfarin

Ceftriaxone may enhance the anticoagulant effect

Celecoxib [1], warfarin ---> SmPC of [1] of EMA

Anticoagulant activity should be monitored in patients taking warfarin or other anticoagulants

Ceritinib [1], warfarin ---> SmPC of [1] of EMA

Co-administration of ceritinib with CYP2C9 substrates known to have narrow therapeutic indices (e.g. phenytoin and warfarin) should be avoided.

Cerivastatin, warfarin

Cerivastatin can enhance the anticoagulant effect

Chloramphenicol, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Chlordiazepoxide, warfarin

The co-administration may decrease the anticoagulant effect

Chlortalidone, warfarin

The co-administration may decrease the anticoagulant effect

Cholestyramine [1], warfarin ---> SmPC of [1] of eMC

Cholestyramine may delay or reduce the absorption of warfarin. Patients should take other drugs at least 1 hour before or 4-6 hours after colestyramine to minimize possible interference with their absorption.

Cilostazol [1], warfarin ---> SmPC of [1] of EMA

Caution is advised in patients receiving both cilostazol and any anticoagulant agent and is contraindicated with 2 or more additional antiplatelet/anticoagulant agents

Cimetidine, warfarin [2] ---> SmPC of [2] of eMC

Cimetidine, enzyme inhibitor, may increase the plasma levels of coumarine and prolong the prothrombin time

Cinacalcet [1], warfarin ---> SmPC of [1] of EMA

Multiple oral doses of cinacalcet did not affect the pharmacokinetics or pharmacodynamics (as measured by prothrombin time and clotting factor VII) of warfarin.

Ciprofloxacin [1], warfarin ---> SmPC of [1] of eMC

Simultaneous administration of ciprofloxacin with a vitamin K antagonist may augment its anti-coagulant effects.

Cisapride, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Clarithromycin [1], warfarin ---> SmPC of [1] of eMC

There is a risk of serious haemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin.

Clindamycin, warfarin

Clindamycin may increase the anticoagulant activity

Clofibrate, warfarin

Clofibrate may enhance the anticoagulant activity

Clopidogrel [1], warfarin ---> SmPC of [1] of EMA

Coadministration of clopidogrel with warfarin increases the risk of bleeding because of independent effects on hemostasis.

Clopidogrel/acetylsalicylic acid [1], warfarin ---> SmPC of [1] of EMA

The co-administration is not recommended since it may increase the intensity of bleedings

Clozapine [1], warfarin ---> SmPC of [1] of eMC

Clozapine may increase the plasma concentration of warfarin due to displacement from plasma proteins

Cobicistat [1], warfarin ---> SmPC of [1] of EMA

Concentrations of warfarin may be affected upon co-administration with cobicistat.

Colesevelam [1], warfarin ---> SmPC of [1] of EMA

Anticoagulant therapy should be monitored closely in patients receiving warfarin or similar agents, since bile acid sequestrants have been shown to reduce absorption of vitamin K and therefore interfere with warfarin's anticoagulant effect.

Conjugated oestrogens/bazedoxifene [1], warfarin ---> SmPC of [1] of EMA

Based on in vitro bazedoxifene plasma protein-binding characteristics, interactions with warfarin, digoxin or diazepam are unlikely.

Corticotropin, warfarin

The co-administration may decrease the anticoagulant effect

Cortisone, warfarin

The co-administration may decrease the anticoagulant effect

Cotrimoxazole [1], warfarin ---> SmPC of [1] of eMC

Effects of warfarin enhanced.

Cyclophosphamide, warfarin

The co-administration may increase or decrease the warfarin effect

CYP3A4 and CYP2C9 inhibitors, warfarin

The inhibition of CYP2C9, CYP3A4 may increase the plasma concentrations of warfarin and therefore may cause an increase in prothrombin time

Dabigatran etexilate [1], warfarin ---> SmPC of [1] of EMA

Concomitant treatment of dabigatran with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter

Dabigatran [1], warfarin ---> SmPC of [1] of EMA

The co-administration may increase the risk of bleeding

Dabrafenib [1], warfarin ---> SmPC of [1] of EMA

Concomitant administration of dabrafenib with warfarin results in decreased warfarin exposure. Caution should be exercised and additional International Normalized Ratio (INR) monitoring is recommended

Daclatasvir [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment of daclatasvir or warfarin is required.

Danazol, warfarin [2] ---> SmPC of [2] of eMC

Danazol can potentiate the action of warfarin.

Dapoxetine [1], warfarin ---> SmPC of [1] of eMC

There have been reports of bleeding abnormalities with SSRIs. Caution is advised in patients taking dapoxetine, particularly in concomitant use anticoagulants (e.g., warfarin)

Daptomycin [1], warfarin ---> SmPC of [1] of EMA

Anticoagulant activity should be monitored for the first several days

Darifenacin [1], warfarin ---> SmPC of [1] of EMA

Standard therapeutic prothrombin time monitoring for warfarin should be continued. The effect of warfarin on prothrombin time was not altered when co-administered with darifenacin.

Darunavir/cobicistat [1], warfarin ---> SmPC of [1] of EMA

Based on theoretical considerations REZOLSTA may alter warfarin plasma concentrations. It is recommended that the international normalised ratio (INR) be monitored when warfarin is co-administered with REZOLSTA.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], warfarin ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI may alter warfarin plasma concentrations. It is recommended that the international normalised ratio (INR) be monitored when warfarin is co-administered with Symtuza.

Darunavir/ritonavir, warfarin ---> SmPC of [darunavir] of EMA

Warfarin concentrations may be affected when co-administered with boosted darunavir. It is recommended that the international normalised ratio (INR) be monitored when warfarin is combined with boosted darunavir.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, warfarin ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EMA

Ombitasvir/paritaprevir/ritonavir administered with or without dasabuvir did not affect the exposures of the CYP2C9 substrate, warfarin. Other CYP2C9 substrates are not expected to require dose adjustments.

Defibrotide [1], warfarin ---> SmPC of [1] of EMA

Concomitant systemic anticoagulant therapy, except for routine maintenance or reopening of central venous line, requires careful monitoring.

Dexibuprofen [1], warfarin ---> SmPC of [1] of eMC

The effects of anticoagulants on bleeding time can be potentiated by NSAIDs.

Dexketoprofen [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anti-coagulants, such as warfarin, due to the high plasma protein binding of dexketoprofen and the inhibition of platelet function and damage to the gastroduodenal mucosa.

Dextran, warfarin

The co-administration may enhance the anticoagulant effect

Dextropropoxyphene, warfarin

Enhancement of anticoagulant effect and increase of prothrombin time

Diazoxide, warfarin

The co-administration may enhance the anticoagulant effect

Diclofenac, warfarin [2] ---> SmPC of [2] of eMC

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Dicloxacillin, warfarin

Dicloxacillin may decrease the anticoagulant effect

Dicoumarol, warfarin

The co-administration may enhance the anticoagulant effect

Dipyridamole [1], warfarin ---> SmPC of [1] of eMC

When dipyridamole was administered concomitantly with warfarin, bleeding was no greater in frequency or severity than that observed when warfarin was administered alone.

Disopyramide [1], warfarin ---> SmPC of [1] of eMC

When prescribing a drug metabolised by CYP3A it should be kept in mind that disopyramide is probably also a substrate of this isozyme and thus competitive inhibition of metabolism might occur, possibly increasing serum levels of these drugs.

Disulfiram, warfarin [2] ---> SmPC of [2] of eMC

Disulfiram potentiates the effect of warfarin

Doxorubicine, warfarin

Interactions with doxorubicin have been reported for warfarin

Doxycycline [1], warfarin ---> SmPC of [1] of eMC

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline.

Dronedarone [1], warfarin ---> SmPC of [1] of EMA

Clinically significant INR elevations (≥5) usually within 1 week after starting dronedarone were reported in patients taking oral anticoagulants.

Drugs with high protein binding, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Dulaglutide [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment of warfarin is necessary when administered with dulaglutide.

Duloxetine [1], warfarin ---> SmPC of [1] of EMA

Increases in INR values have been reported when duloxetine was co-administered to patients treated with warfarin.

Econazole [1], warfarin ---> SmPC of [1] of eMC

Patients taking oral anticoagulants, such as warfarin or acenocoumarol, caution should be exercised and the anticoagulant effect should be monitored more frequently.

Efavirenz [1], warfarin ---> SmPC of [1] of EMA

Increased/decreased plasma concentrations of warfarin

Efavirenz/emtricitabine/tenofovir disoproxil [1], warfarin ---> SmPC of [1] of EMA

Interaction not studied. Plasma concentrations and effects of warfarin or acenocoumarol are potentially increased or decreased by efavirenz. Dose adjustment of warfarin or acenocoumarol may be required when co-administered with Atripla.

Elvitegravir [1], warfarin ---> SmPC of [1] of EMA

Elvitegravir, CYP2C9 inductor, may decrease the plasma levels of warfarin

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], warfarin ---> SmPC of [1] of EMA

Concentrations of warfarin may be affected upon co-administration with Genvoya. It is recommended that the international normalised ratio (INR) be monitored upon co-administration of Genvoya.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], warfarin ---> SmPC of [1] of EMA

Concentrations of warfarin may be affected upon co-administration with cobicistat.

Entacapone [1], warfarin ---> SmPC of [1] of EMA

The control of INR is recommended when entacapone treatment is initiated for patients receiving warfarin.

Enzalutamide [1], warfarin ---> SmPC of [1] of EMA

Enzalutamide, CYP2C9 inductor, may decrease the AUC of warfarin

Enzyme inductors, warfarin

The enzymatic inductor may increase the metabolism of warfarin and decrease its plasma levels and the anticoagulant effect

Enzyme inhibitors, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Eplerenone [1], warfarin ---> SmPC of [1] of eMC

No clinically significant pharmacokinetic interactions have been observed with warfarin. Caution is warranted when warfarin is dosed near the upper limit of therapeutic range.

Eptifibatide [1], warfarin ---> SmPC of [1] of EMA

Eptifibatid did not appear to increase the risk of major and minor bleeding associated with concomitant use of warfarin

Erlotinib [1], warfarin ---> SmPC of [1] of EMA

Interaction with coumarin-derived anticoagulants including warfarin leading to increased International Normalized Ratio (INR) and bleeding events, which in some cases were fatal, have been reported in patients receiving erlotinib.

Erythromycin, warfarin [2] ---> SmPC of [2] of eMC

Erythromycin potentiates the effect of warfarin

Eslicarbazepine [1], warfarin ---> SmPC of [1] of EMA

Co-administration of eslicarbazepine acetate with warfarin showed a small but statistically significant decrease in exposure to S-warfarin.

Esmolol [1], warfarin ---> SmPC of [1] of eMC

Data from an interaction study between esmolol and warfarin showed that concomitant administration does not alter warfarin plasma levels. Esmolol concentrations, however, were equivocally higher when given with warfarin.

Esomeprazole [1], warfarin ---> SmPC of [1] of EMA

Esomeprazole inhibits CYP2C19, the major esomeprazole metabolising enzyme. Thus, when esomeprazole is combined with medicinal products metabolised by CYP2C19, the plasma concentrations of these medicinal products may be increased

Ethacrynic acid, warfarin

The co-administration may enhance the anticoagulant effect

Ethchlorvynol, warfarin

The enzymatic inductor may increase the metabolism of warfarin and decrease its plasma levels and the anticoagulant effect

Ethinyl estradiol, warfarin

Ethinylestradiol may decrease the anticoagulant effect

Etidronate [1], warfarin ---> SmPC of [1] of eMC

There have been isolated reports of patients experiencing changes in their prothrombin times when etidronate was added to warfarin therapy.

Etidronic acid, warfarin [2] ---> SmPC of [2] of eMC

There have been isolated reports of patients experiencing changes in their prothrombin times when etidronate was added to warfarin therapy.

Etoricoxib [1], warfarin ---> SmPC of [1] of eMC

Patients receiving oral anticoagulants should be closely monitored for their prothrombin time INR, particularly in the first few days when therapy with etoricoxib is initiated or the dose of etoricoxib is changed

Etravirine [1], warfarin ---> SmPC of [1] of EMA

Etravirine is expected to increase plasma concentrations of warfarin. It is recommended that the international normalised ratio (INR)be monitored when warfarin is combined with etravirine.

Exenatide [1], warfarin ---> SmPC of [1] of EMA

Increased INR has been spontaneously reported during concomitant use of warfarin and prolonged-release exenatide. INR should be monitored during initiation of prolonged-release exenatide therapy in patients on warfarin and/or cumarol derivatives

Ezetimibe [1], warfarin ---> SmPC of [1] of eMC

There have been post-marketing reports of increased INR in patients who had ezetimibe added to warfarin or fluindione. If ezetimibe is added to coumarin anticoagulant, or fluindione, INR should be appropriately monitored

Ezetimibe/atorvastatin, warfarin

If ATOZET is added to warfarin, another coumarin anticoagulant, or fluindione, INR should be appropriately monitored

Ezetimibe/simvastatine [1], warfarin ---> SmPC of [1] of eMC

There have been post-marketing reports of increased INR in patients who had ezetimibe added to warfarin or fluindione. If ezetimibe is added to coumarin anticoagulant, or fluindione, INR should be appropriately monitored

Febuxostat [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment is necessary for warfarin when administered with febuxostat.

Felodipine [1], warfarin ---> SmPC of [1] of eMC

The high degree of plasma protein binding of felodipine does not appear to affect the unbound fraction of other extensively plasma protein bound drugs

Felodipine/metoprolol, warfarin ---> SmPC of [felodipine] of eMC

The high degree of plasma protein binding of felodipine does not appear to affect the unbound fraction of other extensively plasma protein bound drugs

Fenoprofen, warfarin

The co-administration may enhance the anticoagulant effect

Feprazone, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Fesoterodine [1], warfarin ---> SmPC of [1] of EMA

A clinical study in healthy volunteers has shown that fesoterodine 8 mg once daily has no significant effect on the pharmacokinetics or the anticoagulant activity of a single dose of warfarin.

Fibrates, warfarin [2] ---> SmPC of [2] of eMC

Fibrates potentiate the effect of warfarin

Fluconazole [1], warfarin ---> SmPC of [1] of eMC

During concomitant treatment with fluconazole and warfarin the prothrombin time was prolonged up to 2-fold, probably due to an inhibition of the warfarin metabolism through CYP2C9.

Fluorouracil, warfarin [2] ---> SmPC of [2] of eMC

Marked elevations of prothrombin time and INR have been reported in a few patients stabilised on warfarin therapy following initiation of fluorouracil regimes.

Fluoxetine [1], warfarin ---> SmPC of [1] of eMC

Altered anti-coagulant effects (laboratory values and/or clinical signs and symptoms), with no consistent pattern, but including increased bleeding, have been reported uncommonly when fluoxetine is co-administered with oral anticoagulants.

Flurbiprofen [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anticoagulants such as warfarin

Flutamide, warfarin

Flutamide may increase the prothrombin time

Fluvastatin, warfarin [2] ---> SmPC of [2] of eMC

Isolated incidences of bleeding episodes and/or increases prothrombin times have been reported very rarely in patients on fluvastatin receiving concomitant warfarin or other coumarin derivatives.

Fluvoxamine [1], warfarin ---> SmPC of [1] of eMC

When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin times prolonged.

Fosamprenavir/ritonavir, warfarin ---> SmPC of [fosamprenavir] of EMA

A reinforced monitoring of the International Normalised Ratio is recommended in case of administration of Amprenavir with warfarin or other oral anticoagulants, due to a possible decrease or increase of their antithrombotic effect

Fosaprepitant [1], warfarin ---> SmPC of [1] of EMA

Coadministration of oral aprepitant with warfarin (CYP2C9 substrate) decreased prothrombin time. In patients on chronic warfarin therapy, the INR should be monitored closely for 14 days following the use of fosaprepitant

Fosphenytoin [1], warfarin ---> SmPC of [1] of eMC

Blood levels and/or effects of anticoagulants (warfarin) may be altered by phenytoin

Furosemide, warfarin

The co-administration may enhance the anticoagulant effect

Gadofosveset [1], warfarin ---> SmPC of [1] of EMA

Gadofosveset demonstrated no adverse interaction at clinically relevant concentrations.

Galantamine [1], warfarin ---> SmPC of [1] of eMC

Therapeutic doses of galantamine 24 mg/day had no effect on the kinetics and prothrombin time of warfarin.

Gefitinib [1], warfarin ---> SmPC of [1] of EMA

INR elevations and/or bleeding events have been reported in some patients concomitantly taking warfarin

Gemfibrozil, warfarin [2] ---> SmPC of [2] of eMC

Gemfibrozil may potentiate the effects of oral anticoagulants, which necessitates careful monitoring of the anticoagulant dosing

Gentamicin, warfarin

Gentamicin potentiates the anticoagulant effect

Ginseng, warfarin

The co-administration of ginseng with anti-coagulant effect of coumarin drugs may potentiate the anti-coagulant effect

Gliclazide [1], warfarin ---> SmPC of [1] of eMC

Sulphonylureas may lead to potentiation of anticoagulation during concurrent treatment. Adjustment of the anticoagulant may be necessary.

Glucagon [1], warfarin ---> SmPC of [1] of eMC

Glucagon may increase the anticoagulant effect of warfarin.

Glucosamine, warfarin

The co-administration may enhance the effect of coumarin anticoagulant

Glutethimide, warfarin

The enzymatic inductor may increase the metabolism of warfarin and decrease its plasma levels and the anticoagulant effect

Green tea, warfarin

The co-administration may decrease the anticoagulant effect

Griseofulvin, warfarin [2] ---> SmPC of [2] of eMC

Griseofulvin antagonises the effect of warfarin

Halothane, warfarin

The co-administration may enhance the anticoagulant effect

Ibrutinib [1], warfarin ---> SmPC of [1] of EMA

Warfarin or other vitamin K antagonists should not be administered concomitantly with IMBRUVICA.

Ibuprofen, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Idelalisib [1], warfarin ---> SmPC of [1] of EMA

The co-administration of idelalisib with warfarin may increase the serum concentrations of warfarin. It is recommended that the INR be monitored upon co-administration and following ceasing treatment with idelalisib.

Ifosfamide, warfarin

The co-administration of ifosfamide and warfarin may strongly decrease the blood coagulation and increase the risk of bleeding

Imatinib [1], warfarin ---> SmPC of [1] of EMA

Because of known increased risks of bleeding in conjunction with the use of imatinib (e.g. haemorrhage), patients who require anticoagulation should receive low-molecular-weight or standard heparin, instead of coumarin derivatives such as warfarin.

Imipenem/cilastatin [1], warfarin ---> SmPC of [1] of eMC

There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant agents, including warfarin in patients who are concomitantly receiving antibacterial agents.

Indinavir [1], warfarin ---> SmPC of [1] of EMA

Combined administration may result in increased warfarin levels. Dose adjustment of warfarin may be required.

Indinavir/ritonavir, warfarin ---> SmPC of [indinavir] of EMA

Ritonavir, inductor of CYP1A2 and CYP2C9, may decrease the levels of R warfarin. Monitoring the anticoagulation parameters.

Indometacin, warfarin

The co-administration may enhance the anticoagulant effect

Insulin degludec/liraglutide [1], warfarin ---> SmPC of [1] of EMA

Upon initiation of liraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent monitoring of INR (International Normalised Ratio) is recommended.

Insulin glargine/lixisenatide [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment for warfarin is required when co-administered with lixisenatide; however, frequent monitoring of INR in patients on warfarin and/or coumarin derivatives is recommended at the time of initiation or ending of lixisenatide treatment.

Interferon alfa, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Irbesartan [1], warfarin ---> SmPC of [1] of EMA

Irbesartan is mainly metabolised by CYP2C9 and to a lesser extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was coadministered with warfarin, a medicinal product metabolised by CYP2C9

Isavuconazole [1], warfarin ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Warfarin (CYP2C9 substrate): no dose adjustment required

Isoniazid, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Itraconazol, warfarin [2] ---> SmPC of [2] of eMC

Itraconazole may increase the plasma concentrations of warfarin

Ivabradine [1], warfarin ---> SmPC of [1] of EMA

Specific drug-drug interaction studies have shown no clinically significant effect of the warfarin on pharmacokinetics and pharmacodynamics of ivabradine

Ivacaftor [1], warfarin ---> SmPC of [1] of EMA

Ivacaftor may inhibit CYP2C9. Therefore, monitoring of the INR during co-administration with warfarin is recommended.

Ketoconazole [1], warfarin ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of warfarin. Careful monitoring. INR (international normalised ratio) monitoring recommended.

Ketoprofen, warfarin

Increased risk of bleeding

Ketorolac, warfarin

Ketorolac is contraindicated in combination with anti-coagulants, such as warfarin since co-administration of NSAIDs and anti-coagulants may cause an enhanced anti-coagulant effect

Lacosamide [1], warfarin ---> SmPC of [1] of EMA

Co-administration of warfarin with lacosamide does not result in a clinically relevant change in the pharmacokinetics and pharmacodynamics of warfarin.

Leflunomide [1], warfarin ---> SmPC of [1] of EMA

There have been case reports of increased prothrombin time, when leflunomide and warfarin were co-administered. Therefore, when warfarin or another coumarin anticoagulant is co-administered, close INR follow-up and monitoring is recommended.

Lenalidomide [1], warfarin ---> SmPC of [1] of EMA

Close monitoring of warfarin concentration is advised during the treatment.

Lercanidipine [1], warfarin ---> SmPC of [1] of eMC

The co-administration of 20 mg lercanidipine to healthy volunteers given fasted did not alter the pharmacokinetics of warfarin.

Lesinurad [1], warfarin ---> SmPC of [1] of EMA

Lesinurad led to a decrease in exposure of R-warfarin (the less active enantiomer) and had no effect on the exposure of S-warfarin (the more active enantiomer).

Letermovir [1], warfarin ---> SmPC of [1] of EMA

Letermovir has the potential to decrease the exposure of CYP2C9 and/or CYP2C19 substrates potentially resulting in subtherapeutic levels.

Levamisole, warfarin

The co-administration may enhance the anticoagulant effect

Levetiracetam [1], warfarin ---> SmPC of [1] of EMA

Co-administration with digoxin, oral contraceptives and warfarin did not influence the pharmacokinetics of levetiracetam.

Levodopa/carbidopa/entacapone [1], warfarin ---> SmPC of [1] of EMA

The control of INR is recommended when entacapone treatment is initiated for patients receiving warfarin.

Levofloxacin [1], warfarin ---> SmPC of [1] of EMA

Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin).

Levothyroxine [1], warfarin ---> SmPC of [1] of eMC

Levothyroxine increases the effect of anticoagulants and it may be necessary to reduce the anticoagulation dosage if excessive, hypoprothrombinaemia and bleeding are to be avoided.

Linagliptin [1], warfarin ---> SmPC of [1] of EMA

In clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of warfarin

Linagliptin/metformin [1], warfarin ---> SmPC of [1] of EMA

Multiple daily doses of 5 mg linagliptin did not alter the pharmacokinetics of S(-) or R(+) warfarin, a CYP2C9 substrate, administered in a single dose.

Linezolid [1], warfarin ---> SmPC of [1] of eMC

When warfarin was added to linezolid therapy at steady-state, there was a 10% reduction in mean maximum INR on co-administration with a 5% reduction in AUC INR.

Liothyronine [1], warfarin ---> SmPC of [1] of eMC

Liothyronine sodium therapy may potentiate the action of anticoagulants (coumarins and phenindione).

Liraglutide [1], warfarin ---> SmPC of [1] of EMA

Upon initiation of liraglutide treatment in patients on warfarin or other coumarin derivatives, more frequent monitoring of INR (International Normalised Ratio) is recommended.

Lixisenatide [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment for warfarin is required when co-administered with lixisenatide; however, frequent monitoring of INR in patients on warfarin and/or coumarin derivatives is recommended at the time of initiation or ending of lixisenatide treatment.

Lomitapide [1], warfarin ---> SmPC of [1] of EMA

In patients taking coumarins (such as warfarin) and lomitapide concomitantly, INR should be determined before starting lomitapide and monitored regularly with dosage of coumarins adjusted as clinically indicated

Lopinavir/ritonavir [1], warfarin ---> SmPC of [1] of EMA

The induction of CYP2C9 by lopinavir/ritonavir may decrease the plasma concentrations of warfarin. It is recommended that INR be monitored

Lornoxicam, warfarin

The NSAID may enhance the effects of anticoagulant agent

Lovastatine, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Lumacaftor/ivacaftor [1], warfarin ---> SmPC of [1] of EMA

The international normalised ratio (INR) should be monitored when warfarin co-administration with lumacaftor/ivacaftor is required. Lumacaftor/ivacaftor may alter the exposure of warfarin.

Lumiracoxib, warfarin

Caution should be exercised when co-administering lumiracoxib with substrates of CYP2C9 that have a narrow therapeutic index

Macitentan [1], warfarin ---> SmPC of [1] of EMA

The pharmacodynamic effect of warfarin on International Normalized Ratio (INR) was not affected by macitentan. The pharmacokinetics of macitentan and its active metabolite were not affected by warfarin.

Magaldrate, warfarin

Decreased absorption of warfarin. It is recommended to administer the two substances at least 2-3 hours apart.

Mefenamic acid, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Memantin [1], warfarin ---> SmPC of [1] of EMA

Close monitoring of prothrombin time or INR is advisable for patients concomitantly treated with oral anticoagulants.

Meprobamate [1], warfarin ---> SmPC of [1] of eMC

The co-administration may decrease the anticoagulant effect

Mercaptopurine [1], warfarin ---> SmPC of [1] of EMA

Inhibition of the anticoagulant effect of warfarin, when given with 6 -mercaptopurine, has been reported. Monitoring of the INR (International Normalised Ratio) value is recommended during concomitant administration with oral anticoagulants.

Meropenem [1], warfarin ---> SmPC of [1] of eMC

Simultaneous administration of antibiotics with warfarin may augment its anti-coagulant effects.

Mesalazine [1], warfarin ---> SmPC of [1] of eMC

Administration of mesalazine with coumarin-type anticoagulants could result in decreased anticoagulant activity. Prothrombin time should be closely monitored if this combination is essential.

Metamizole, warfarin

The co-administration may enhance or decrease the anticoagulant effect

Methoxsalen, warfarin

The co-administration may displace methoxsalen from its albumin binding and increase the photosensitivity

Methyldopa, warfarin

The co-administration may enhance the anticoagulant effect

Methylphenidate, warfarin [2] ---> SmPC of [2] of eMC

Methylphenidate potentiates the effect of warfarin

Metreleptin [1], warfarin ---> SmPC of [1] of EMA

The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted.

Metronidazole [1], warfarin ---> SmPC of [1] of eMC

Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anticoagulants. Dosage of the latter may require reducing.

Mianserin, warfarin

Mianserin may potentiate the anticoagulant effect of coumarin drug by inhibiting its metabolism by the liver

Midostaurin [1], warfarin ---> SmPC of [1] of EMA

Medicinal products with a narrow therapeutic range that are substrates of CYP2C9 (e.g. warfarin) should be used with caution when administered concomitantly with midostaurin and may need dose adjustment to maintain optimal exposure

Mirtazapine [1], warfarin ---> SmPC of [1] of eMC

Mirtazapine may cause a small but statistically significant increase in the international normalized ratio

Mitotane [1], warfarin ---> SmPC of [1] of EMA

Mitotane, inductor of hepatic microsomal enzymes, accelerates the metabolism of the anticoagulant. Closely monitoring

Modafinil [1], warfarin ---> SmPC of [1] of eMC

Due to possible suppression of CYP2C9 by modafinil the clearance of warfarin may be decreased when modafinil is administered concomitantly.

Nabumetone [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anti-coagulants, such as warfarin; its concomitant administration with nabumetone should be undertaken with caution and overdose signals carefully monitored.

Nalidixic acid, warfarin

Possible increase of plasma concentration and anticoagulant effect of warfarin due to displacement from plasma proteins

Naproxen [1], warfarin ---> SmPC of [1] of eMC

NSAIDs may enhance the effects of anti-coagulants

Nateglinide [1], warfarin ---> SmPC of [1] of EMA

In vivo, nateglinide has no clinically relevant effect on the pharmacokinetics of medicinal products metabolised by CYP2C9 and CYP3A4.

Nebivolol [1], warfarin ---> SmPC of [1] of eMC

Nebivolol does not affect the pharmacokinetics and pharmacodynamics of warfarin.

Nelfinavir [1], warfarin ---> SmPC of [1] of EMA

Coadministration of warfarin and nelfinavir may affect concentrations of warfarin. It is recommended that the international normalized ratio (INR) be monitored carefully during treatment with nelfinavir, especially when commencing therapy.

Nevirapine [1], warfarin ---> SmPC of [1] of EMA

Potentiation or decrease of the anticoagulant effect. Close monitoring of the coagulation

Nilotinib [1], warfarin ---> SmPC of [1] of EMA

Due to lack of steady-state data, control of warfarin pharmacodynamic markers (INR or PT) following initiation of nilotinib therapy (at least during the first 2 weeks) is recommended.

Norfloxacin, warfarin

Quinolone may increase the effect anticoagulant of warfarin

NSAID, warfarin [2] ---> SmPC of [2] of eMC

NSAIDs potentiate the effect of warfarin

Obeticholic acid [1], warfarin ---> SmPC of [1] of EMA

International normalised ratio (INR) is decreased following co-administration of warfarin and obeticholic acid.

Octreotide [1], warfarin ---> SmPC of [1] of eMC

Drugs mainly metabolised by CYP3A4 and which have a low therapeutic index should be only used with octreotide with caution.

Ofloxacin, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Olanzapine [1], warfarin ---> SmPC of [1] of EMA

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism was found

Olmesartan medoxomil [1], warfarin ---> SmPC of [1] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin

Olmesartan medoxomil/amlodipine [1], warfarin ---> SmPC of [1] of eMC

Olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin

Olsalazine [1], warfarin ---> SmPC of [1] of eMC

Increased prothrombin time in patients taking concomitant warfarin has been reported.

Ombitasvir/paritaprevir/ritonavir [1], warfarin ---> SmPC of [1] of EMA

Ombitasvir/paritaprevir/ritonavir administered with or without dasabuvir did not affect the exposures of the CYP2C9 substrate, warfarin. Other CYP2C9 substrates are not expected to require dose adjustments.

Omeprazole [1], warfarin ---> SmPC of [1] of eMC

As omeprazole is metabolised in the liver through cytochrome P450, it can prolong the elimination of warfarin

Opicapone [1], warfarin ---> SmPC of [1] of EMA

Clinical interaction studies conducted with warfarin showed no effect of opicapone on the pharmacodynamics of warfarin, a substrate of CYP2C9.

Oral anticoagulants, warfarin

Increased anticoagulant activity. More frequent monitoring of prothrombin time/INR values should be considered

Oral contraceptives, warfarin [2] ---> SmPC of [2] of eMC

Oral contraceptives antagonise the effect of warfarin

Oritavancin [1], warfarin ---> SmPC of [1] of EMA

Co-administration of oritavancin and warfarin may result in higher exposure of warfarin (resulting in 31% increase in the mean area under the curve (AUC) of warfarin), which may increase the risk of bleeding

Orlistat [1], warfarin ---> SmPC of [1] of EMA

When warfarin or other anticoagulants are given in combination with orlistat, international normalized ratio (INR) values should be monitored

Ospemifene [1], warfarin ---> SmPC of [1] of EMA

Ospemifene did not cause a clinically meaningful change in the exposure to the CYP2C9 substrates, indicating that ospemifene does not affect those enzyme activities in vivo to a clinically significant extent.

Oxaprozin, warfarin

The co-administration may enhance the anticoagulant effect

Oxcarbazepine [1], warfarin ---> SmPC of [1] of eMC

Warfarin had no effect on the pharmacokinetics of MHD.

Pantoprazole [1], warfarin ---> SmPC of [1] of EMA

In patients treated with coumarin anticoagulants monitoring of prothrombin time/INR is recommended after initiation, termination or during irregular use of pantoprazole.

Paracetamol [1], warfarin ---> SmPC of [1] of eMC

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Paraldehyde, warfarin

The co-administration may decrease the anticoagulant effect

Parecoxib [1], warfarin ---> SmPC of [1] of EMA

Anticoagulant therapy should be monitored, particularly during the first few days after initiating parecoxib therapy in patients receiving warfarin or other anticoagulants, since these patients have an increased risk of bleeding complications.

Pazopanib [1], warfarin ---> SmPC of [1] of EMA

Pazopanib does not have a clinically relevant effect on the pharmacokinetics of caffeine (CYP1A2 probe substrate), warfarin (CYP2C9 probe substrate), or omeprazole (CYP2C19 probe substrate) in cancer patients.

Pefloxacine, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Peginterferon alfa-2b [1], warfarin ---> SmPC of [1] of EMA

Elevation of blood concentrations of warfarin has been reported when administered in combination with other interferon preparations and therefore care should be taken. Metabolism of other medicines in the liver may be suppressed.

Pelargonium sidoides, warfarin

Pelargonium sidoides may enhance the effect of anticoagulants. The combination is not recommended

Pentobarbital, warfarin

The co-administration may decrease the anticoagulant effect

Pentosan polysulfate sodium [1], warfarin ---> SmPC of [1] of EMA

A study in healthy subjects revealed no pharmacokinetic or pharmacodynamic interactions between therapeutic doses of warfarin and pentosan polysulfate sodium.

Pergolide, warfarin

Careful monitoring of anticoagulation should be performed, with adjustments of dosage as necessary

Perphenazine [1], warfarin ---> SmPC of [1] of eMC

Perphenazine may affect action of anticoagulants and increase the bleeding time

Phenazone, warfarin

The co-administration of phenazone and warfarin enhances the effect of warfarin

Phenobarbital, warfarin

The enzymatic inductor may increase the metabolism of warfarin and decrease its plasma levels and the anticoagulant effect

Phenylbutazone, warfarin [2] ---> SmPC of [2] of eMC

NSAIDs may enhance the effects of oral anti-coagulants (e.g. warfarin, dicoumarol)

Phenytoin, warfarin [2] ---> SmPC of [2] of eMC

Phenytoin antagonises the effect of warfarin

Pioglitazone [1], warfarin ---> SmPC of [1] of EMA

Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of warfarin

Piperaquine, warfarin

The CYP3A4 inhibition may increase plasma levels of warfarin

Piracetam, warfarin

Piracetam can enhance the anticoagulant effect

Piroxicam [1], warfarin ---> SmPC of [1] of eMC

NSAIDs, including piroxicam, may enhance the effects of anticoagulants, such as warfarin. Therefore, the use of piroxicam with concomitant anticoagulant such as warfarin should be avoided.

Pitavastatin, warfarin

The co-administration may increase the international normalised ratio (INR). Appropriate monitoring of INR is desirable.

Pitolisant [1], warfarin ---> SmPC of [1] of EMA

With other CYP3A4, CYP2B6 (e.g. efavirenz, bupropion), CYP2C (e.g. repaglinide, phenytoin, warfarin), P-gp (e.g. dabigatran, digoxin) and UGT (e.g. morphine, paracetamol, irinotecan) substrates, caution should be made

Pixantrone [1], warfarin ---> SmPC of [1] of EMA

Warfarin is partially metabolised by CYP1A2, therefore, a theoretical concern exists with regard to co-administration of this medicinal product and the effect inhibition of its metabolism might have on its intended action.

Platelet aggregation inhibitors, warfarin [2] ---> SmPC of [2] of eMC

Any concomitant anti-platelet drugs should be used with caution due to an increased risk of bleeding.

Pomalidomide [1], warfarin ---> SmPC of [1] of EMA

The effect of dexamethasone on warfarin is unknown. Close monitoring of warfarin concentration is advised during treatment.

Prasugrel [1], warfarin ---> SmPC of [1] of EMA

Because of the potential for increased risk of bleeding, warfarin (or other coumarin derivatives) and Efient should be co-administered with caution

Pravastatine [1], warfarin ---> SmPC of [1] of eMC

Bioavailability parameters at steady state for pravastatin were not altered following administration with warfarin.

Pregnancy, warfarin [2] ---> SmPC of [2] of eMC

Warfarin is contraindicated in pregnancy in the first and third trimester.

Primidone, warfarin [2] ---> SmPC of [2] of eMC

Primidone therapy may lead to altered pharmacokinetics in concomitantly administered drugs, whose metabolism may be increased and lead to lowered plasma levels and/or a shorter half-life.

Proguanil [1], warfarin ---> SmPC of [1] of eMC

Proguanil may potentiate the effect of warfarin and other coumarin based anticoagulants which may lead to an increase in the risk of haemorrhage.

Propafenone [1], warfarin ---> SmPC of [1] of eMC

Propafenone has been shown to increase the plasma levels of oral anticoagulants (e.g. warfarin), with an accompanying increase in prothrombin time, which may require a reduction in the dose of oral anticoagulants.

Propranolol, warfarin [2] ---> SmPC of [2] of eMC

Propranolol may cause a reduction in clearance and an increase in plasma concentrations of warfarin.

Propylthiouracil, warfarin

The co-administration may enhance or decrease the anticoagulant effect

Proteolytic enzymes enriched in bromelain [1], warfarin ---> SmPC of [1] of EMA

NexoBrid, when absorbed, is an inhibitor of CYP2C8 and CYP2C9. This should be taken into account if it is used in patients receiving CYP2C9 substrates

Pyrimethamine [1], warfarin ---> SmPC of [1] of eMC

The high protein binding exhibited by pyrimethamine may prevent protein binding by other compounds. This could affect the efficacy or toxicity of the concomitant drug depending on the levels of unbound drug.

Quinolones, warfarin ---> SmPC of [norfloxacin] of eMC

Quinolone may increase the effect anticoagulant of warfarin

Raloxifene [1], warfarin ---> SmPC of [1] of EMA

Modest decreases in the prothrombin time. The prothrombin time should be monitored

Ranitidine, warfarin [2] ---> SmPC of [2] of eMC

There have been reports of altered prothrombin time with coumarin anticoagulants. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.

Regorafenib [1], warfarin ---> SmPC of [1] of EMA

Blood counts and coagulation parameters should be monitored in patients treated with anticoagulants (e.g. warfarin and phenprocoumon) or other concomitant medicinal products that increase the risk of bleeding.

Retinol, warfarin

Possibly increased anticoagulant effect and risk of bleeding

Rifamicyn, warfarin

The co-administration may decrease the anticoagulant effect

Rifampicin [1], warfarin ---> SmPC of [1] of eMC

Rifampicin is a potent inducer of certain cytochrome P-450 enzymes. Coadministration of rifampicin with drugs that are also metabolised through these cytochrome P-450 enzymes may accelerate the metabolism and reduce the activity of these other drugs.

Riociguat [1], warfarin ---> SmPC of [1] of EMA

Concomitant treatment of riociguat and warfarin did not alter prothrombin time induced by the anticoagulant.

Ritonavir [1], warfarin ---> SmPC of [1] of EMA

Ritonavir, inductor of CYP1A2 and CYP2C9, may decrease the levels of R warfarin and may lead to reduced anticoagulation. Monitoring the anticoagulation parameters.

Rivaroxaban [1], warfarin ---> SmPC of [1] of EMA

Concomitant treatment with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter.

Rivastigmine [1], warfarin ---> SmPC of [1] of EMA

The increase in prothrombin time induced by warfarin is not affected by administration of rivastigmine.

Rofecoxib, warfarin

The co-administration may enhance the anticoagulant effect

Rosuvastatin [1], warfarin ---> SmPC of [1] of eMC

The co-administration may increase the international normalised ratio (INR). Appropriate monitoring of INR is desirable.

Roxithromycin, warfarin

The co-administration may increase the prothrombin time or the international normalized ratio (INR)

Rucaparib [1], warfarin ---> SmPC of [1] of EMA

When co-administering medicinal products that are CYP2C9 substrates with a narrow therapeutic index (e.g., warfarin, phenytoin), dose adjustments may be considered, if clinically indicated.

Rufinamide [1], warfarin ---> SmPC of [1] of EMA

It is recommended that patients treated with substances that are metabolised by the CYP3A4 enzyme system are to be carefully monitored for two weeks at the start of, or after the end of treatment with rufinamide, or after any marked change in the dose.

Salicylates, warfarin

Salicylates may enhance the anticoagulant effect with risk of bleeding

Saquinavir, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Saquinavir/ritonavir, warfarin ---> SmPC of [saquinavir] of EMA

Concentrations of warfarin may be affected when co-administered with Invirase/ritonavir. INR monitoring recommended

Secobarbital, warfarin

The enzymatic inductor may increase the metabolism of warfarin and decrease its plasma levels and the anticoagulant effect

Secukinumab [1], warfarin ---> SmPC of [1] of EMA

Secukinumab, IL-17A inhibitor, may lower exposure of CYP450-metabolised co-medications. Therefore, a clinically relevant effect on CYP450 substrates with a narrow therapeutic index cannot be excluded.

Selexipag [1], warfarin ---> SmPC of [1] of EMA

The pharmacokinetics of selexipag and its active metabolite are not affected by warfarin. Selexipag did not influence the pharmacodynamic effect of warfarin on the international normalised ratio.

Semaglutide [1], warfarin ---> SmPC of [1] of EMA

Upon initiation of semaglutide treatment in patients on warfarin or other coumarin derivatives, frequent monitoring of INR is recommended.

Sertraline [1], warfarin ---> SmPC of [1] of EMA

The co-administration may increase the prothrombin time

Sevelamer carbonate [1], warfarin ---> SmPC of [1] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride, which contains the same active moiety as sevelamer carbonate, had no effect on the bioavailability of digoxin, warfarin, enalapril or metoprolol.

Sevelamer hydrochloride [1], warfarin ---> SmPC of [1] of EMA

In interaction studies in healthy volunteers, sevelamer hydrochloride had no effect on the bioavailability of warfarin

Sildenafil [1], warfarin ---> SmPC of [1] of EMA

Population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin).

Simeprevir [1], warfarin ---> SmPC of [1] of EMA

No dose adjustment is required. However, it is recommended that the international normalised ratio (INR) be monitored.

Simvastatine, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Sitaxentan [1], warfarin ---> SmPC of [1] of EMA

Concomitant treatment with sitaxentan sodium resulted in a 2.4 fold increase in S-warfarin exposure.

Sodium valproate [1], warfarin ---> SmPC of [1] of eMC

The anticoagulant effect of warfarin and other coumarin anticoagulants may be increased following displacement from plasma protein binding sites by valproic acid.

Sodium zirconium cyclosilicate [1], warfarin ---> SmPC of [1] of EMA

In a clinical drug-drug interaction study conducted in healthy subjects co-administration did not result in clinically meaningful drug-drug interactions and no dose adjustments are required.

Solifenacin [1], warfarin ---> SmPC of [1] of eMC

Intake of solifenacin did not alter the pharmacokinetics of R-warfarin or S-warfarin or their effect on prothrombin time.

Sonidegib [1], warfarin ---> SmPC of [1] of EMA

Sonidegib is a competitive inhibitor of CYP2B6 and CYP2C9 in vitro. Substances that are substrates of CYP2B6 and CYP2C9 enzymes with narrow therapeutic range (e.g. warfarin, acenocoumarol, efavirenz, methadone) should be avoided.

Sorafenib [1], warfarin ---> SmPC of [1] of EMA

Should be monitored regularly for changes in prothrombin time, INR or clinical bleeding episodes

Spironolactone, warfarin

The co-administration may decrease the anticoagulant effect

St. John's wort [1], warfarin ---> SmPC of [1] of eMC

Herbal preparations containing St John's Wort (Hypericum perforatum) must not be used whilst taking warfarin due to a proven risk of decreased plasma concentrations and reduced clinical effects of warfarin.

Stanozolol, warfarin

Stanozolol may enhance the risk of bleeding

Statins, warfarin [2] ---> SmPC of [2] of eMC

Statins may potentiate the effect of warfarin

Sucralfate, warfarin [2] ---> SmPC of [2] of eMC

Concomitant administration of sucralfate may reduce the bioavailability of warfarin. The bioavailability may be restored by separating the administration from sucralfate by 2 hours.

Sucroferric oxyhydroxide [1], warfarin ---> SmPC of [1] of EMA

Drug-drug interaction studies have been conducted in healthy subjects with losartan, furosemide, digoxin, warfarin, and omeprazole. Co-administration of Velphoro did not affect the bioavailability of these products as measured by the AUC.

Sulfamethizole, warfarin

The co-administration may enhance the anticoagulant effect

Sulfamethoxazol, warfarin [2] ---> SmPC of [2] of eMC

Sulfamethoxazole potentiates the effect of warfarin

Sulfinpyrazone, warfarin

The co-administration may enhance the anticoagulant effect

Sulfonylureas, warfarin ---> SmPC of [gliclazide] of eMC

Sulphonylureas may lead to potentiation of anticoagulation during concurrent treatment. Adjustment of the anticoagulant may be necessary.

Sultiame, warfarin

The co-administration may increase the plasma levels of warfarin. Adjustment of the dose may be required

Sunitinib [1], warfarin ---> SmPC of [1] of EMA

Periodic monitoring by complete blood counts (platelets), coagulation factors (PT/INR), and physical examination

Tadalafil [1], warfarin ---> SmPC of [1] of EMA

Tadalafil (10 mg and 20 mg) had no clinically significant effect on exposure (AUC) to S-warfarin or R-warfarin (CYP2C9 substrate), nor did tadalafil affect changes in prothrombin time induced by warfarin.

Tamoxifen, warfarin [2] ---> SmPC of [2] of eMC

Tamoxifen potentiates the effect of warfarin

Tamsulosin [1], warfarin ---> SmPC of [1] of eMC

Warfarin may increase the elimination rate of tamsulosin

Tegafur, warfarin

Patients receiving coumarin anticoagulants (e.g. warfarin or acenocoumarol) should be closely monitored for their prothrombin time INR

Telaprevir [1], warfarin ---> SmPC of [1] of EMA

Increased/decreased plasma concentrations of warfarin. It is recommended that the international normalized ratio

Telithromycin [1], warfarin ---> SmPC of [1] of EMA

Although telithromycin has no clinically relevant pharmacokinetic or pharmacodynamic interaction with warfarin after single dose administration, more frequent monitoring of prothrombin time/INR values should be considered during concomitant treatment.

Terbinafine [1], warfarin ---> SmPC of [1] of eMC

Rare cases of changes in INR and/or prothrombin time have been reported in patients receiving terbinafine concomitantly with warfarin.

Teriflunomide [1], warfarin ---> SmPC of [1] of EMA

When warfarin is co-administered with teriflunomide, close INR follow-up and monitoring is recommended.

Tetracyclines, warfarin [2] ---> SmPC of [2] of eMC

Broad spectrum antibiotics may potentiate the effect of warfarin by reducing the gut flora which produce vitamin K.

Tezacaftor/ivacaftor [1], warfarin ---> SmPC of [1] of EMA

Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) is recommended during co-administration of warfarin with Symkevi given in combination with ivacaftor.

Thalidomide [1], warfarin ---> SmPC of [1] of EMA

Close monitoring of INR values is advised during thalidomide-prednisone combination treatment as well as during the first weeks after ending these treatments

Thiazides, warfarin

Thiazides may decrease the anticoagulant effect

Thrombolytics, warfarin [2] ---> SmPC of [2] of eMC

Fibrinolytic drugs such as streptokinase and alteplase are contraindicated in patients receiving warfarin.

Tiagabine [1], warfarin ---> SmPC of [1] of eMC

Tiagabine does not have any clinically significant effect on the plasma concentrations of warfarin

Tiaprofenic acid, warfarin [2] ---> SmPC of [2] of eMC

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding

Tibolone [1], warfarin ---> SmPC of [1] of eMC

Since tibolone may increase blood fibrinolytic activity, it may enhance the effect of anticoagulants. This effect has been demonstrated with warfarin.

Ticagrelor [1], warfarin ---> SmPC of [1] of EMA

Ticagrelor is not a CYP2C9 inhibitor and unlikely to alter the CYP2C9 mediated metabolism of medicinal products like warfarin and tolbutamide.

Ticarcillin, warfarin

The co-administration may enhance the anticoagulant effect

Ticlopidine, warfarin

The co-administration may enhance the anticoagulant effect

Tigecycline [1], warfarin ---> SmPC of [1] of EMA

Since tigecycline may prolong both prothrombin time (PT) and activated partial thromboplastin time (aPTT), the relevant coagulation tests should be closely monitored when tigecycline is co-administered with anticoagulants

Tipranavir/ritonavir, warfarin ---> SmPC of [tipranavir] of EMA

Aptivus, co-administered with low dose ritonavir, when combined with warfarin may be associated with changes in INR (International Normalised Ratio) values, and may affect anticoagulation (thrombogenic effect) or increase the risk of bleeding.

Tirofiban [1], warfarin ---> SmPC of [1] of eMC

The use of platelet aggregation inhibitors with warfarin increases the risk of bleeding

Tissue-type plasminogen activator, warfarin

The co-administration may enhance the anticoagulant effect

Tocilizumab [1], warfarin ---> SmPC of [1] of EMA

When starting or stopping therapy with tocilizumab, patients taking medicinal products which are individually adjusted and are metabolised via CYP450 3A4, 1A2 or 2C9 should be monitored as doses may need to be increased to maintain therapeutic effect.

Tolcapone [1], warfarin ---> SmPC of [1] of EMA

Since clinical information is limited regarding the combination of warfarin and tolcapone, coagulation parameters should be monitored when these drugs are co-administered.

Tolterodine [1], warfarin ---> SmPC of [1] of eMC

Drug interaction studies have shown no interactions with warfarin

Tolvaptan [1], warfarin ---> SmPC of [1] of EMA

In healthy subjects, tolvaptan, a CYP3A4 substrate, had no effect on the plasma concentrations of warfarin

Tramadol [1], warfarin ---> SmPC of [1] of eMC

There have been isolated reports of interaction with coumarin anticoagulants resulting in an increased INR. Care should be taken if treatment with tramadol is started in patients taking anticoagulants.

Trazodone [1], warfarin ---> SmPC of [1] of eMC

There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.

Triflusal, warfarin

The metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid, impairs the serum protein binding of warfarin and increases the plasma levels of warfarin.

Trimethoprim/sulfamethoxazol, warfarin

Co-trimoxazole may inhibit the metabolism of warfarin and increase the anticoagulant effect

Valproic acid [1], warfarin ---> SmPC of [1] of eMC

The anticoagulant effect of warfarin and other coumarin anticoagulants may be increased following displacement from plasma protein binding sites by valproic acid.

Valsartan [1], warfarin ---> SmPC of [1] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and warfarin

Vardenafil [1], warfarin ---> SmPC of [1] of EMA

No significant interactions were shown when warfarin was co-administered with vardenafil

Varenicline [1], warfarin ---> SmPC of [1] of EMA

Varenicline did not alter the pharmacokinetics of warfarin. Smoking cessation itself may result in changes to warfarin pharmacokinetics

Vemurafenib [1], warfarin ---> SmPC of [1] of EMA

When a single dose of warfarin was co-administered after repeat dosing with vemurafenib for 15 days, some patients exhibited increased warfarin (CYP2C9)

Venetoclax [1], warfarin ---> SmPC of [1] of EMA

Because venetoclax was not dosed to steady state, it is recommended that the international normalized ratio (INR) be monitored closely in patients receiving warfarin.

Venlafaxine, warfarin

Possible prolongation of bleeding time. Caution is recommended

Vildagliptin, warfarin ---> SmPC of [vildagliptin/metformin] of EMA

Drug-drug interaction studies with digoxin (P-glycoprotein substrate) and warfarin (CYP2C9 substrate) in healthy subjects have shown no clinically relevant pharmacokinetic interactions after coadministration with vildagliptin.

Vildagliptin/metformin [1], warfarin ---> SmPC of [1] of EMA

Drug-drug interaction studies with digoxin (P-glycoprotein substrate) and warfarin (CYP2C9 substrate) in healthy subjects have shown no clinically relevant pharmacokinetic interactions after coadministration with vildagliptin.

Viloxazine, warfarin

The enzymatic inhibitor may decrease the metabolism of warfarin and increase its plasma levels, the anticoagulant effect and the bleeding risk

Vitamin A, warfarin

Possibly increased anticoagulant effect and risk of bleeding

Vitamin E, warfarin

Potentiation of the anticoagulant effect

Vitamin K, warfarin

The co-administration may decrease or abolish the anticoagulant effect

Vorapaxar [1], warfarin ---> SmPC of [1] of EMA

When vorapaxar was co-administered with warfarin, there were no alterations in the pharmacokinetics/pharmacodynamics of warfarin. The coadministration of vorapaxar with anticoagulants e.g., warfarin and new oral anticoagulants (NOACs), should be avoided.

Voriconazole [1], warfarin ---> SmPC of [1] of EMA

The inhibition of CYP2C9 by voriconazole may increase the plasma concentrations of warfarin. Maximum increase in prothrombin time was approximately 2-fold.

Warfarin, zafirlukast [2] ---> SmPC of [2] of eMC

Co-administration with warfarin results in an increase in maximum prothrombin time by approximately 35%. The interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system.

CONTRAINDICATIONS of Warfarin

- Known hypersensitivity to warfarin or to any of the excipients

- Haemorrhagic stroke (see section 4.4 for further details)

- Clinically significant bleeding

- Within 72 hours of major surgery with risk of severe bleeding (for information on other surgery, see section 4.4)

- Within 48 hours postpartum

- Pregnancy (first and third trimesters, see section 4.6)

- Drugs where interactions may lead to a significantly increased risk of bleeding

http://www.medicines.org.uk/emc/