warfarin (Rx)

Brand and Other Names:Coumadin, Jantoven
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

powder for injection

  • 5mg/vial (discontinued)

tablet

  • 1mg
  • 2mg
  • 2.5mg
  • 3mg
  • 4mg
  • 5mg
  • 6mg
  • 7.5mg
  • 10mg

Venous Thrombosis

Prophylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE)

Initial dose: 2-5 mg PO/IV qDay for 2 days, OR 10 mg PO for 2 days in healthy individuals

Initiate warfarin on day 1 or 2 of LMWH or unfractionated heparin therapy and overlap until desired INR, THEN discontinue heparin

Check INR after 2 days and adjust dose according to results

Typical maintenance dose ranges between 2 and 10 mg/day

Consider dosage based on genotype (see Genomic Considerations)

DVT and PE treatment

  • Initiate warfarin on day 1 or 2 of parenteral anticoagulation therapy (eg, LMWH or unfractionated heparin)
  • Overlap warfarin and parenteral anticoagulant for at least 5 days until desired INR (>2.0) maintained for 24 hours, then discontinue parenteral therapy

INR range and treatment duration

  • Maintain an INR of 2.0-3.0
  • Surgery-provoked DVT or PE: Treatment duration of 3 months
  • Transient (reversible) risk factor-induced DVT or PE: Treatment duration of 3 months
  • First unprovoked proximal DVT or PE with low or moderate bleeding risk: Extended treatment consideration with periodic (ie, annual) risk-benefit analysis
  • First unprovoked proximal DVT or PE with high bleeding risk: Treatment duration of 3 months
  • First unprovoked distal DVT regardless of bleeding risk: Treatment duration of 3 months
  • Second unprovoked DVT or PE with low or moderate bleeding risk: Extended treatment
  • Second unprovoked DVT or PE with high bleeding risk: Treatment duration of 3 months
  • DVT/PE and active cancer: Extended treatment, with periodic risk-benefit analysis (ACCP recommends LMWH over vitamin K antagonist therapy)
  • Prevention of venous thromboembolism for total knee arthroplasty, total hip arthroplasty, and hip fracture surgery: Minimum treatment duration of 10-14 days, with a recommendation to extend outpatient therapy to 35 days (ACCP recommends LMWH over vitamin K antagonist therapy)

Stroke & Thromboembolism

Prophylaxis and treatment of systemic embolic complications (eg, stroke) associated with atrial fibrillation (AF)

Initial dose: 2-5 mg PO/IV qDay × 2 days, OR 10 mg PO × 2 days in healthy individuals

Check INR after 2 days and adjust dose according to results

Typical maintenance dose ranges between 2-10 mg/day

Consider dosage based on genotype (see Genomic Considerations)

ACCP guidelines recommend dabigatran 150 mg PO BID over adjusted-dose warfarin therapy for AF unless both AF and mitral stenosis are present

INR range and treatment duration

  • Nonvalvular AF: Maintain an INR of 2.0-3.0
  • AF and stable CAD: Adjusted-dose warfarin therapy (INR 2.0-3.0) without aspirin
  • AF with high stroke risk and placement of stent: Triple therapy of dose-adjusted warfarin (INR 2.0-3.0), clopidogrel, and aspirin; for 1 month if bare metal stent; for 3-6 months for drug-eluting stent
  • AF with intermediate to high stroke risk without stent placement: 12 months of warfarin therapy (INR 2.0-3.0) with single antiplatelet regimen
  • AF for more than 48 hours to undergo cardioversion: Warfarin therapy (INR 2.0-3.0) for 3 weeks prior to and 4 weeks after cardioversion

Indications for indefinite treatment duration

  • Persistent or paroxysmal nonvalvular AF in patients with a high risk of stroke: Ie, patients who have risk factors for stroke, such as prior ischemic stroke, transient ischemic attack, or systemic embolism or who have 2 of the following risk factors--age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus
  • Persistent or paroxysmal nonvalvular AF in patients with an intermediate risk of ischemic stroke: Ie, patients who have 1 of the following risk factors--age >75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitus
  • AF and mitral stenosis
  • ≥2 episodes of documented DVT or PE

Cardiac Valve Replacement

Prophylaxis and treatment of thromboembolic complications associated with cardiac valve replacement

Initial dose: 2-5 mg PO/IV qDay × 2 days, OR 10 mg PO × 2 days in healthy individuals

Check INR after 2 days and adjust dose according to results

Typical maintenance dose ranges between 2 and 10 mg/day

Consider dosage based on genotype (see Genomic Considerations)

INR and treatment duration

  • Mitral bioprosthetic valve: INR 2.0-3.0 for a 3-month treatment duration; if other risk factors for thromboembolism are present (ie, AF, previous thromboembolism, left ventricular dysfunction), a longer duration may be necessary
  • Aortic mechanical valve: INR 2.0-3.0 for indefinite treatment duration
  • Mitral mechanical valve, caged ball or caged disk valve, or both aortic and mitral mechanical valves: INR 2.5-3.5 for indefinite treatment duration
  • Mechanical valves include bileaflet mechanical valves and Medtronic Hall tilting disk valves

Post-Myocardial Infarction

Reduction in the risk of death, recurrent MI, and thromboembolic events (eg, stroke, systemic embolization) after MI

Initial dose: 2-5 mg PO/IV qDay × 2 days, OR 10 mg PO × 2 days in healthy individuals

Check INR after 2 days and adjust dose according to results

Typical maintenance dose ranges between 2 and 10 mg/day

Consider dosage based on genotype (see Genomic Considerations)

INR and treatment duration

  • Maintain INR between 2.0 and 3.0
  • In patients who have not had stenting and who have anterior MI and left ventricular (LV) thrombus or high risk of LV thrombus (ie, ejection fraction <40%, anteroapical wall-motion abnormality), treatment involves dual therapy of warfarin (INR 2.0-3.0) and low-dose aspirin 75-100 mg, daily; treatment duration is 3 months, after which warfarin is discontinued
  • In patients who have had bare-metal stent placement and who have anterior MI and LV thrombus or high risk of LV thrombus (ejection fraction <40%, anteroapical wall-motion abnormality), treatment involves triple therapy of warfarin (INR 2.0-3.0), low-dose aspirin, and clopidogrel 75 mg, daily for 1 month, followed by warfarin (INR 2.0-3.0) and single antiplatelet therapy for second and third month, after which warfarin is discontinued
  • In patients who have had drug-eluting stent placement and who have anterior MI and LV thrombus or high risk of LV thrombus (ejection fraction <40%, anteroapical wall-motion abnormality), treatment involves triple therapy of warfarin (INR 2.0-3.0), low-dose aspirin, and clopidogrel 75 mg, daily for 3-6 months, after which warfarin is discontinued

Rheumatic Valve Disease (Off-label)

Rheumatic valve disease with any of the following: Atrial diameter >55 mm, left atrial thrombus, atrial fibrillation, and previous systemic embolism

Maintain INR 2.0-3.0 indefinitely

Cryptogenic Stroke and Patent Foramen Ovale With DVT (Off-label)

Maintain INR between 2.0 and 3.0 for 3 months

Cardioembolic Stroke or TIA (Off-label)

Maintain INR between 2.0 and 3.0 indefinitely

ACCP guidelines recommend dabigatran 150 mg PO twice daily over dose-adjusted warfarin therapy

Systolic LV Dysfunction (Off-label)

Systolic LV dysfunction without established CAD but with identified acute LV thrombus (eg, Takotsubo cardiomyopathy)

Maintain INR between 2.0 and 3.0 for at least 3 months

Antiphospholipid Antibody Syndrome (Off-label)

Antiphospholipid antibody syndrome with previous arterial or venous thromboembolism

Maintain INR between 2.0 and 3.0 indefinitely

Genomic Considerations

ACCP 2012 guidelines recommend against using pharmacogenetic testing for guiding doses

CYP2C9 and vitamin K epoxide reductase complex, subunit 1 (VKORC1) genotype information can assist in selecting starting dose

If genotype information unavailable, usual starting dose is 2-5 mg/day (modify based on other patient factors)

Range of expected therapeutic doses based on CYP2C9 and VKORC1 genotypes are listed below

VKORC1-GG

  • CYP2C9 *1/*1: 5-7 mg
  • CYP2C9 *1/*2: 5-7 mg
  • CYP2C9 *1/*3: 3-4 mg
  • CYP2C9 *2/*2: 3-4 mg
  • CYP2C9 *2/*3: 3-4 mg
  • CYP2C9 *3/*3: 0.5-2 mg

VKORC1-AG

  • CYP2C9 *1/*1: 5-7 mg
  • CYP2C9 *1/*2: 3-4 mg
  • CYP2C9 *1/*3: 3-4 mg
  • CYP2C9 *2/*2: 3-4 mg
  • CYP2C9 *2/*3: 0.5-2 mg
  • CYP2C9 *3/*3: 0.5-2 mg

VKORC1-AA

  • CYP2C9 *1/*1: 3-4 mg
  • CYP2C9 *1/*2: 3-4 mg
  • CYP2C9 *1/*3: 0.5-2 mg
  • CYP2C9 *2/*2: 0.5-2 mg
  • CYP2C9 *2/*3: 0.5-2 mg
  • CYP2C9 *3/*3: 0.5-2 mg

Dosage Modifications

Hepatic impairment: May potentiate warfarin response because of decreased metabolism and impaired synthesis of clotting factors

Dosing Considerations

Indication determines intensity and duration of therapy

Individualized doses and monitoring of PT/INR are necessary

Monitoring frequency should be daily or once every few days until stabilized; once stable, q4-6 weeks or longer may be appropriate (eg, 12 weeks)

Not all factors causing warfarin dose variability are known, but they include age, race, sex, body weight, concomitant medications, and comorbidities, in addition to genetic factors

Lower starting doses (ie, 2-5 mg/day × 2 days) recommended with the elderly, hepatic impairment, poor nutrition, CHF, high bleeding risk, debilitated patients, heart valve replacement, concomitant medications known to increase warfarin effect, or individuals suspected of having genomic variants

Perioperative management recommendations: Hold warfarin therapy approximately 5 days before surgery; resume warfarin 12-24 hr after surgery; bridge anticoagulation during interruption in patients at high thromboembolism risk

Minor procedures and dental procedures: See ACCP guidelines for specific recommendations

Warfarin has no direct effect on an established thrombus, nor does it reverse ischemic tissue damage

Systemic atheroemboli and cholesterol microemboli; some cases have progressed to necrosis or death; discontinue therapy if such emboli occur

Pregnant women with mechanical heart valves: Therapy may cause fetal harm; however, benefits may outweigh the risks

Dosage Forms & Strengths

powder for injection

  • 5mg/vial (discontinued)

tablets

  • 1mg
  • 2mg
  • 2.5mg
  • 3mg
  • 4mg
  • 5mg
  • 6mg
  • 7.5mg
  • 10mg

Thrombosis

Prevention/treatment: If baseline INR is 1.0-1.3, administer loading dose of 0.1-0.2 mg/kg PO qDay × 1 day; check INR on days 2-4 and adjust daily dose to maintain INR between 2.0 and 3.0 (unless valve replacement indicates a higher range)  

Use 0.1 mg/kg to initiate therapy with liver impairment or in patients who have had a Fontan procedure

Typical maintenance dose: 0.09-0.33 mg/kg/day, with infants <12 months old often requiring doses at high end of range

Dosing considerations

  • Consistent anticoagulation in children is difficult and requires close supervision and frequent dose adjustments
  • Refer to ACCP recommendations or institutional protocol for treatment duration dependent on indication
  • Infants and children receiving vitamin K-supplemented nutrition (including infant formulas): May be resistant to warfarin therapy
  • Infants with human-milk diet: May be sensitive to warfarin therapy

Dosing Considerations

Hepatic impairment

  • Hepatic impairment may potentiate warfarin response because of decreased metabolism and impaired synthesis of clotting factors
  • Load: 0.1 mg/kg PO qDay × 2 days
  • Typical maintenance dose: 0.1 mg/kg PO qDay; adjust dose to achieve desired INR
  • Common maintenance dose range: 0.05-0.34 mg/kg PO qDay

Anticoagulation

Lower doses required to produce therapeutic level of anticoagulation

Initial: ≤5 mg PO qDay

Maintenance: 2-5 mg PO qDay

Dosing Considerations

Elderly show greater than expected PT/INR response to anticoagulant effects of warfarin, possibly because of decreased hepatic function resulting in decreased warfarin metabolism and impaired synthesis of clotting factors

Caution should be used in elderly individuals who have increased risk of hemorrhage

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Interactions

Interaction Checker

and warfarin

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            Contraindicated (3)

            • apixaban

              warfarin and apixaban both increase anticoagulation. Contraindicated.

            • defibrotide

              defibrotide increases effects of warfarin by pharmacodynamic synergism. Contraindicated. Coadministration of defibrotide is contraindicated with antithrombotic/fibrinolytic drugs. This does not include use for routine maintenance or reopening of central venous lines.

            • mifepristone

              mifepristone, warfarin. Other (see comment). Contraindicated. Comment: Mifepristone may lead to excessive post abortion bleeding in pts. on anticoagulant therapy.

            Serious - Use Alternative (125)

            • abciximab

              warfarin, abciximab. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • allopurinol

              allopurinol increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • amiodarone

              amiodarone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • amobarbital

              amobarbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • anagrelide

              warfarin, anagrelide. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • antithrombin alfa

              antithrombin alfa and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • antithrombin III

              antithrombin III and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • argatroban

              argatroban and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • azithromycin

              azithromycin increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • bazedoxifene/conjugated estrogens

              bazedoxifene/conjugated estrogens decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • bemiparin

              bemiparin and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • bivalirudin

              bivalirudin and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • bremelanotide

              bremelanotide will decrease the level or effect of warfarin by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • butabarbital

              butabarbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • butalbital

              butalbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • capecitabine

              capecitabine increases effects of warfarin by unspecified interaction mechanism. Avoid or Use Alternate Drug. Monitor INR and prothrombin time.

            • carbamazepine

              carbamazepine will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cefamandole

              cefamandole increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

            • cefazolin

              cefazolin increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

            • cefdinir

              cefdinir increases effects of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity.

            • cefditoren

              cefditoren increases effects of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity.

            • cefotetan

              cefotetan increases effects of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity.

            • cefoxitin

              cefoxitin will increase the level or effect of warfarin by Other (see comment). Avoid or Use Alternate Drug. Decr vitamin K-producing intestinal flora may increase INR after a few days.

              cefoxitin increases effects of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity.

            • cefpodoxime

              cefpodoxime will increase the level or effect of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity

            • ceftriaxone

              ceftriaxone increases effects of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity.

            • cefuroxime

              cefuroxime will increase the level or effect of warfarin by anticoagulation. Avoid or Use Alternate Drug. cephalosporins may decrease prothrombin activity

            • ceritinib

              ceritinib increases levels of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use of CYP2C9 substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP2C9 during treatment with ceritinib; if use of these medications is unavoidable, consider dose.

            • chloral hydrate

              chloral hydrate increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • chloramphenicol

              chloramphenicol increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • cilostazol

              warfarin, cilostazol. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • cimetidine

              cimetidine will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ciprofibrate

              ciprofibrate increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

              ciprofibrate increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • ciprofloxacin

              ciprofloxacin will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Quinolone antibiotics such as ciprofloxacin may enhance the anticoagulant effects of warfarin. Important to monitor INR/prothrombin time and toxic effects of warfarin. Patients receiving this combination should be closely monitored for adverse effects.

            • clarithromycin

              clarithromycin increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • clotrimazole

              clotrimazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • conjugated estrogens

              conjugated estrogens decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • dabigatran

              dabigatran and warfarin both increase anticoagulation. Avoid or Use Alternate Drug. Both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.

            • dabrafenib

              dabrafenib will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Dabrafenib induces CYP3A4 and possibly other enzymes including CYP2C9 that affect warfarin metabolism

            • dalteparin

              dalteparin and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • danazol

              danazol increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • dipyridamole

              warfarin, dipyridamole. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • duloxetine

              duloxetine increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • edoxaban

              edoxaban, warfarin. Either increases toxicity of the other by anticoagulation. Avoid or Use Alternate Drug. Both drugs have the potential to cause bleeding, monitor closely. Promptly evaluate any signs or symptoms of blood loss. Long-term concomitant treatment with edoxaban and other anticoagulants is not recommended. Short-term coadministration may be needed for patients transitioning to or from edoxaban.

            • efavirenz

              efavirenz will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug.

            • enoxaparin

              enoxaparin and warfarin both increase anticoagulation. Avoid or Use Alternate Drug. Additive effects are intended when both drugs are prescribed as indicated for treatment of DVT

            • eptifibatide

              warfarin, eptifibatide. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • erdafitinib

              warfarin will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

            • erythromycin base

              erythromycin base will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              erythromycin base increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              erythromycin ethylsuccinate increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              erythromycin lactobionate increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              erythromycin stearate increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • estradiol

              estradiol decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • estrogens conjugated synthetic

              estrogens conjugated synthetic decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • estropipate

              estropipate decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. The use of estrogen-containing contraceptives and coumarin derivatives should be avoided to avoid risk of thromboembolic disorders.

              ethinylestradiol decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • fenofibrate

              fenofibrate increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

              fenofibrate increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • fenofibrate micronized

              fenofibrate micronized increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

              fenofibrate micronized increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • fenofibric acid

              fenofibric acid increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

              fenofibric acid increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • fluconazole

              fluconazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • fluoxymesterone

              fluoxymesterone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • fondaparinux

              fondaparinux and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • gemfibrozil

              gemfibrozil increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

              gemfibrozil increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • heparin

              heparin and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • ifosfamide

              ifosfamide, warfarin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug. Monitor for increased INR/effects of coumarin derivatives when ifosfamide is initiated/dose increased, and decreased INR/effects when ifosfamide is discontinued/dose decreased.

            • imatinib

              imatinib will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Because warfarin is metabolized by CYP2C9 and CYP3A4, patients taking imatinib who require anticoagulation should receive low-molecular weight or standard heparin instead of warfarin.

            • itraconazole

              itraconazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              itraconazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoconazole

              ketoconazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              ketoconazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • levomilnacipran

              levomilnacipran, warfarin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

            • levonorgestrel intrauterine

              levonorgestrel intrauterine, warfarin. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of thromboembolic disorders.

            • levonorgestrel oral

              levonorgestrel oral, warfarin. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of thromboembolic disorders.

            • levothyroxine

              levothyroxine increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

            • liothyronine

              liothyronine increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

            • lorlatinib

              lorlatinib will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures of the substrate. If concomitant use is unavoidable, increase CYP3A substrate dosage in accordance with approved product labeling.

            • mesterolone

              mesterolone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • mestranol

              mestranol decreases effects of warfarin by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.

            • metronidazole

              metronidazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • miconazole vaginal

              miconazole vaginal increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • milnacipran

              milnacipran increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • nafcillin

              nafcillin decreases effects of warfarin by increasing hepatic clearance. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              nefazodone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • nitazoxanide

              nitazoxanide, warfarin. Either increases levels of the other by plasma protein binding competition. Avoid or Use Alternate Drug. the active metabolite of nitazoxanide is highly protein bound; avoid use of warfarin with nitazoxanide.

            • oxandrolone

              oxandrolone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • oxymetholone

              oxymetholone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • pefloxacin

              pefloxacin will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • pentobarbital

              pentobarbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • phenindione

              phenindione and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • phenobarbital

              phenobarbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • piperacillin

              piperacillin increases effects of warfarin by anticoagulation. Avoid or Use Alternate Drug. Piperacillin can inhibit platelet aggregation.

            • posaconazole

              posaconazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • prasugrel

              warfarin, prasugrel. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • primidone

              primidone decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • protamine

              protamine and warfarin both increase anticoagulation. Avoid or Use Alternate Drug.

            • quinine

              quinine increases effects of warfarin by unknown mechanism. Avoid or Use Alternate Drug.

            • rifabutin

              rifabutin will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir, warfarin. Other (see comment). Avoid or Use Alternate Drug. Comment: Variable effect on warfarin levels. Initial frequent monitoring of the INR during co-administration is indicated.

            • roxithromycin

              roxithromycin increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • secobarbital

              secobarbital decreases effects of warfarin by increasing metabolism. Avoid or Use Alternate Drug.

            • sertraline

              sertraline increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • siponimod

              warfarin will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • St John's Wort

              St John's Wort will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sulfadiazine

              sulfadiazine increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

              sulfadiazine increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • sulfamethoxazole

              sulfamethoxazole increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

              sulfamethoxazole increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • sulfisoxazole

              sulfisoxazole increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

              sulfisoxazole increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

            • tamoxifen

              tamoxifen increases effects of warfarin by unknown mechanism. Avoid or Use Alternate Drug.

            • tenecteplase

              warfarin and tenecteplase both increase anticoagulation. Avoid or Use Alternate Drug.

            • tesamorelin

              tesamorelin will decrease the level or effect of warfarin by altering metabolism. Avoid or Use Alternate Drug. Monitor INR

            • testosterone

              testosterone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • testosterone buccal system

              testosterone buccal system increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • testosterone intranasal

              testosterone intranasal increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug. Androgens may inhibit warfarin metabolism and/or potentiate anticoagulant effects by affecting the coagulation system.

            • testosterone topical

              testosterone topical increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • thyroid desiccated

              thyroid desiccated increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

            • tibolone

              tibolone increases effects of warfarin by pharmacodynamic synergism. Avoid or Use Alternate Drug.

            • ticlopidine

              warfarin, ticlopidine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • tirofiban

              warfarin, tirofiban. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.

            • trazodone

              trazodone increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • venlafaxine

              venlafaxine increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • vitamin K1 (phytonadione)

              vitamin K1 (phytonadione) decreases effects of warfarin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for decreased prothrombin time or therapeutic effects.

            • voriconazole

              voriconazole increases levels of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

            • zanubrutinib

              warfarin, zanubrutinib. Either increases effects of the other by anticoagulation. Avoid or Use Alternate Drug. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

            Monitor Closely (302)

            • acalabrutinib

              acalabrutinib increases effects of warfarin by anticoagulation. Use Caution/Monitor. Coadministration of acalabrutinib with antiplatelets or anticoagulants may further increase risk of hemorrhage. Monitor for signs of bleeding and consider the benefit-risk of withholding acalabrutinib for 3-7 days presurgery and postsurgery depending upon the type of surgery and the risk of bleeding.

            • aceclofenac

              warfarin and aceclofenac both increase anticoagulation. Modify Therapy/Monitor Closely.

            • acemetacin

              warfarin and acemetacin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • acetaminophen

              acetaminophen increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • agrimony

              warfarin and agrimony both increase anticoagulation. Modify Therapy/Monitor Closely.

            • alfalfa

              warfarin and alfalfa both increase anticoagulation. Modify Therapy/Monitor Closely.

            • alpelisib

              warfarin will increase the level or effect of alpelisib by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely.

              alpelisib will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • alteplase

              warfarin and alteplase both increase anticoagulation. Modify Therapy/Monitor Closely.

            • American ginseng

              warfarin and American ginseng both increase anticoagulation. Modify Therapy/Monitor Closely.

            • amikacin

              amikacin increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • amiodarone

              amiodarone will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              amobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              amobarbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amoxicillin

              amoxicillin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Amoxicillin may enhance anticoagulant effect of vitamin K antagonists.

            • ampicillin

              ampicillin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • anamu

              warfarin and anamu both increase anticoagulation. Use Caution/Monitor.

            • anticholinergic/sedative combos

              anticholinergic/sedative combos decreases levels of warfarin by increasing metabolism. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

            • aprepitant

              aprepitant will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Aprepitant is a CYP2C9 inducer so coadministration with warfarin may result in a clinically significant decrease in INR. Monitor INR closely in patients on chronic warfarin therapy.

            • armodafinil

              armodafinil will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              armodafinil will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aspirin

              warfarin and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely. The need for simultaneous use of low-dose aspirin and warfarin are common for patients with cardiovascular disease; monitor closely.

            • aspirin rectal

              warfarin and aspirin rectal both increase anticoagulation. Modify Therapy/Monitor Closely.

            • aspirin/citric acid/sodium bicarbonate

              warfarin and aspirin/citric acid/sodium bicarbonate both increase anticoagulation. Modify Therapy/Monitor Closely. The need for simultaneous use of low-dose aspirin and warfarin are common for patients with cardiovascular disease; monitor closely.

            • atazanavir

              atazanavir will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azapropazone

              azapropazone increases effects of warfarin by plasma protein binding competition. Use Caution/Monitor.

            • azathioprine

              azathioprine decreases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • azficel-T

              azficel-T, warfarin. Other (see comment). Use Caution/Monitor. Comment: Coadministration with anticoagulants or antiplatelets may increase bruising or bleeding at biopsy and/or injection sites; concomitant use not recommended. Decisions regarding continued use or cessation of anticoagulants or antiplatelets should be made by a physician.

            • betrixaban

              warfarin, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

            • bicalutamide

              bicalutamide increases effects of warfarin by pharmacodynamic synergism. Use Caution/Monitor. Prothrombin times should be closely monitored in patient already receiving coumarin anticoagulants who are started on bicalutamide.

            • blinatumomab

              blinatumomab increases levels of warfarin by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

            • bortezomib

              bortezomib will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Clinical and laboratory monitoring is warranted in combining bortezomib with agents with narrow therapeutic ranges, such as warfarin.

            • bosentan

              bosentan will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              bosentan will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brodalumab

              brodalumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • budesonide

              budesonide will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              budesonide, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • bupropion

              bupropion increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Altered PT/INR infrequently associated with hemorrhagic or thrombotic complications were observed when bupropion was administered with warfarin. Monitor INR when bupropion is added to existing warfarin regimen.

            • butabarbital

              butabarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              butabarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              butabarbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              butalbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              butalbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cannabidiol

              cannabidiol will increase the level or effect of warfarin by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

            • caplacizumab

              caplacizumab, warfarin. Either increases effects of the other by anticoagulation. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              carbamazepine will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              carbamazepine decreases levels of warfarin by increasing metabolism. Use Caution/Monitor.

            • cefaclor

              cefaclor increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • cefdinir

              cefdinir increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • cefixime

              cefixime increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • cefotaxime

              cefotaxime increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • cefpodoxime

              cefpodoxime increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • cefprozil

              cefprozil increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • ceftazidime

              ceftazidime increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • ceftibuten

              ceftibuten increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • ceftriaxone

              ceftriaxone increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • cefuroxime

              cefuroxime increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • celecoxib

              warfarin and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

            • chitosan

              chitosan increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Chitosan can decrease GI absorption of vitamin K, enhancing anticoagulant effects.

            • cholestyramine

              cholestyramine decreases levels of warfarin by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • choline magnesium trisalicylate

              warfarin and choline magnesium trisalicylate both increase anticoagulation. Modify Therapy/Monitor Closely.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              cimetidine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • cinnamon

              warfarin and cinnamon both increase anticoagulation. Modify Therapy/Monitor Closely.

            • citalopram

              citalopram increases levels of warfarin by decreasing metabolism. Use Caution/Monitor. Coadministration of warfarin and citalopram increased prothrombin time by 5%. Use caution with coadministration and monitor patient.

            • clarithromycin

              clarithromycin increases toxicity of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased risk of hemorrage; monitor INR and prothrombin times frequently.

            • clindamycin

              clindamycin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • clopidogrel

              warfarin, clopidogrel. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Enhanced risk of hemorrhage; additive effects may occur when simultaneous use is clinically required .

            • cobicistat

              cobicistat, warfarin. Other (see comment). Use Caution/Monitor. Comment: Effect unknown; monitor INR .

            • colesevelam

              colesevelam will decrease the level or effect of warfarin by Mechanism: inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Administer warfarin at least 4 hr before colesevelam. Monitor INR frequently during colesevelam initiation or discontinuance.

            • collagenase clostridium histolyticum

              warfarin increases toxicity of collagenase clostridium histolyticum by anticoagulation. Use Caution/Monitor. Collagenase clostridium histolyticum has high incidence of ecchymosis/contusion at injection site; avoid concomitant anticoagulants (except for low-dose aspirin, ie, up to 150 mg/day).

            • conivaptan

              conivaptan will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              conjugated estrogens, vaginal decreases effects of warfarin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.

            • cordyceps

              warfarin and cordyceps both increase anticoagulation. Modify Therapy/Monitor Closely.

            • cornsilk

              cornsilk decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor. Cornsilk contains vitamin K; consume a consistent amount daily.

            • cortisone

              cortisone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              cortisone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • cyclophosphamide

              cyclophosphamide increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Anticoagulant effect is increased. Monitor coagulation parameters during and after cyclophosphamide therapy. Adjust the warfarin dose as needed.

            • cyclosporine

              cyclosporine will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • danshen

              warfarin and danshen both increase anticoagulation. Use Caution/Monitor.

            • darifenacin

              darifenacin will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              darunavir will decrease the level or effect of warfarin by unspecified interaction mechanism. Use Caution/Monitor. Monitor INR before initiating. Increase monitoring with concurrent therapy.

            • dasatinib

              dasatinib will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasiglucagon

              dasiglucagon increases effects of warfarin by unknown mechanism. Use Caution/Monitor. High doses of dasiglucagon may enhance anticoagulant effects of vitamin K antagonists.

            • deferasirox

              deferasirox will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              deflazacort, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • devil's claw

              warfarin and devil's claw both increase anticoagulation. Use Caution/Monitor.

            • dexamethasone

              dexamethasone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              dexamethasone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diclofenac

              warfarin and diclofenac both increase anticoagulation. Modify Therapy/Monitor Closely.

            • dicloxacillin

              dicloxacillin decreases levels of warfarin by increasing metabolism. Use Caution/Monitor.

            • diflunisal

              warfarin and diflunisal both increase anticoagulation. Modify Therapy/Monitor Closely.

              diflunisal increases effects of warfarin by plasma protein binding competition. Use Caution/Monitor.

            • disulfiram

              disulfiram will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              disulfiram increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

            • dong quai

              warfarin and dong quai both increase anticoagulation. Modify Therapy/Monitor Closely.

            • dronabinol

              dronabinol increases levels of warfarin by plasma protein binding competition. Modify Therapy/Monitor Closely. Dronabinol is highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered highly protein-bound drugs. This has not been confirmed in vivo. Caution with narrow therapeutic index drugs that are highly protein bound when initiating or increasing the dose of dronabinol.

            • dronedarone

              dronedarone will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dulaglutide

              dulaglutide, warfarin. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

            • dupilumab

              dupilumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • econazole topical

              econazole topical increases effects of warfarin by decreasing metabolism. Use Caution/Monitor. Most cases reported use of econazole under occlusive bandage, genital application, or application to large body surface area which may increase the systemic absorption.

            • efavirenz

              efavirenz will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elbasvir/grazoprevir

              elbasvir/grazoprevir increases toxicity of warfarin by anticoagulation. Use Caution/Monitor. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment; frequent monitoring of INR values recommended during treatment and post-treatment follow-up.

            • eluxadoline

              eluxadoline increases levels of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

            • epoprostenol

              warfarin and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.

            • erythromycin base

              erythromycin base will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of warfarin by increasing metabolism. Use Caution/Monitor. S-warfarin serum concentrations may be decreased. Monitor coagulation parameters (INR) when initiating or discontinuing eslicarbazepine in patients

            • estrogens esterified

              estrogens esterified decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor. Estrogens may theoretically reduce the effect of anticoagulants.

            • ethanol

              ethanol, warfarin. Mechanism: altering metabolism. Use Caution/Monitor. Avoid alcohol ingestion; acute, excessive EtOH ingestion (binge drinking) decreases .

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethotoin

              warfarin increases levels of ethotoin by unknown mechanism. Use Caution/Monitor.

              ethotoin, warfarin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time.

            • etodolac

              warfarin and etodolac both increase anticoagulation. Modify Therapy/Monitor Closely.

            • etravirine

              etravirine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • exenatide injectable solution

              exenatide injectable solution, warfarin. Other (see comment). Use Caution/Monitor. Comment: Exenatide may increase INR and possibly increase bleeding when coadministered with warfarin. Monitor prothrombin (PT) time more frequently after starting or changing dose of exenatide. Once a stable PT time is established, monitor PT times at intervals usually recommended for patients taking warfarin.

            • exenatide injectable suspension

              exenatide injectable suspension, warfarin. Other (see comment). Use Caution/Monitor. Comment: Exenatide may increase INR and possibly increase bleeding when coadministered with warfarin. Monitor prothrombin (PT) time more frequently after starting or changing dose of exenatide. Once a stable PT time is established, monitor PT times at intervals usually recommended for patients taking warfarin.

            • felbamate

              felbamate will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • fenbufen

              warfarin and fenbufen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • fennel

              warfarin and fennel both increase anticoagulation. Modify Therapy/Monitor Closely.

            • fenoprofen

              warfarin and fenoprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ferric maltol

              ferric maltol, warfarin. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

            • feverfew

              warfarin and feverfew both increase anticoagulation. Modify Therapy/Monitor Closely.

            • fish oil

              fish oil, warfarin. Other (see comment). Use Caution/Monitor. Comment: Patients taking fish oil and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. Monitor for changes in INR.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of warfarin by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

            • fleroxacin

              fleroxacin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Ciprofloxacin, norfloxacin, & ofloxacin are most likely to interact w/warfarin; data for other quinolones is conflicting. Monitor INR closely.

            • fluconazole

              fluconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              fluconazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              fludrocortisone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • fluorouracil

              fluorouracil increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. Due to the thrombocytopenic effects of fluorouracil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.

            • fluoxetine

              fluoxetine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              fluoxetine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • flurbiprofen

              warfarin and flurbiprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • flutamide

              flutamide increases effects of warfarin by pharmacodynamic synergism. Use Caution/Monitor. Increases in prothrombin time have been noted in patients receiving long-term warfarin therapy after flutamide was initiated. Close monitoring of prothrombin time is recommended.

            • fluvastatin

              fluvastatin increases effects of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • food

              food decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor. Specifically, vitamin K rich foods (e.g., dark leafy green vegetables).

            • forskolin

              warfarin and forskolin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • fosamprenavir

              fosamprenavir will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              warfarin increases levels of fosphenytoin by unknown mechanism. Use Caution/Monitor.

              fosphenytoin, warfarin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time.

            • garlic

              warfarin and garlic both increase anticoagulation. Modify Therapy/Monitor Closely.

            • gefitinib

              gefitinib increases effects of warfarin by unknown mechanism. Modify Therapy/Monitor Closely. Gefitinib prescribing information reports some patients receiving concomitant warfarin experienced increased INR and/or bleeding.

            • gemcitabine

              gemcitabine increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. The anticoagulant effect of warfarin may be increased.

            • gemifloxacin

              gemifloxacin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

              gemifloxacin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Ciprofloxacin, norfloxacin, & ofloxacin are most likely to interact w/warfarin; data for other quinolones is conflicting. Monitor INR closely.

            • ginger

              warfarin and ginger both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ginkgo biloba

              warfarin and ginkgo biloba both increase anticoagulation. Modify Therapy/Monitor Closely.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir increases and warfarin decreases Other (see comment). Effect of interaction is not clear, use caution. Use Caution/Monitor. Warfarin is a substrate of OATP and BCRP, which has been suggested to cause fluctuations in warfarin absorption; close monitoring of INR values is recommended during treatment and post-treatment follow-up.

            • glucagon

              glucagon increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • glucagon intranasal

              glucagon intranasal increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • green tea

              green tea decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor. Combination may decrease warfarin efficacy. Potential for increased risk of bleeding. Important to monitor INR.

            • griseofulvin

              griseofulvin will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • guselkumab

              guselkumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • hemin

              warfarin, hemin. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Hemin degradation product (ie, hematin) may produce coagulopathy (eg, thrombocytopenia, platelet degranulation) and cause mild anticoagulant effects.

            • horse chestnut seed

              warfarin and horse chestnut seed both increase anticoagulation. Modify Therapy/Monitor Closely.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              hydrocortisone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • ibrutinib

              ibrutinib will increase the level or effect of warfarin by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

            • ibuprofen

              warfarin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ibuprofen IV

              warfarin and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.

            • icosapent

              icosapent, warfarin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time; monitor periodically if coadministered with other drugs that affect bleeding.

            • indinavir

              indinavir will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • indomethacin

              warfarin and indomethacin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • iodine (radioactive)

              iodine (radioactive) decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              isoniazid will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              isoniazid will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ivermectin

              ivermectin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Rare interaction.

            • ixekizumab

              ixekizumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • ketoconazole

              ketoconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • ketoprofen

              warfarin and ketoprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ketorolac

              warfarin and ketorolac both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ketorolac intranasal

              warfarin and ketorolac intranasal both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ledipasvir/sofosbuvir

              ledipasvir/sofosbuvir increases toxicity of warfarin by anticoagulation. Use Caution/Monitor. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment; frequent monitoring of INR values recommended during treatment and post-treatment follow-up.

            • leflunomide

              leflunomide will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • letermovir

              letermovir will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Monitor INR.

            • levocarnitine

              levocarnitine will increase the level or effect of warfarin by unknown mechanism. Use Caution/Monitor. INR may increase in patients receiving warfarin therapy; monitor INR levels following initiation of levocarnitine therapy and after dose adjustments

            • levofloxacin

              levofloxacin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

              levofloxacin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Ciprofloxacin, norfloxacin, & ofloxacin are most likely to interact w/warfarin; data for other quinolones is conflicting. Monitor INR closely.

            • lofepramine

              lofepramine increases levels of warfarin by decreasing metabolism. Use Caution/Monitor.

            • lomitapide

              lomitapide will increase the level or effect of warfarin by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Increases plasma concentration of R(+)-warfarin and S(-)-warfarin and INR significantly. Monitor INR especially after changing lomitapide dosage. Adjust warfarin dose as necessary.

            • lornoxicam

              warfarin and lornoxicam both increase anticoagulation. Modify Therapy/Monitor Closely.

            • lovastatin

              lovastatin increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor, warfarin. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

              lumacaftor/ivacaftor increases levels of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor INR when coadministration required. The less potent warfarin R-enantiomer is metabolized by CYP3A4.

            • lumefantrine

              lumefantrine will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • marijuana

              marijuana will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • meclofenamate

              warfarin and meclofenamate both increase anticoagulation. Modify Therapy/Monitor Closely.

            • mefenamic acid

              warfarin and mefenamic acid both increase anticoagulation. Modify Therapy/Monitor Closely.

            • melatonin

              melatonin increases effects of warfarin by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.

            • meloxicam

              warfarin and meloxicam both increase anticoagulation. Modify Therapy/Monitor Closely.

            • mercaptopurine

              mercaptopurine decreases effects of warfarin by unknown mechanism. Use Caution/Monitor. Inhibition of the anticoagulant effect of warfarin, when given with mercaptopurine, has been reported.

            • mesalamine

              mesalamine decreases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • methimazole

              methimazole decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor.

            • methylphenidate

              methylphenidate will increase the level or effect of warfarin by unknown mechanism. Use Caution/Monitor.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              methylprednisolone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • methyltestosterone

              methyltestosterone increases levels of warfarin by decreasing metabolism. Use Caution/Monitor. Monitor INR.

            • metronidazole

              metronidazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              metronidazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mexiletine

              mexiletine will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              miconazole vaginal will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mistletoe

              warfarin increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • mitotane

              mitotane will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor INR for a change in anticoagulant dosage requirements when warfarin is coadministered with mitotane (strong CYP3A4 inducer)

            • modafinil

              modafinil will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              modafinil will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • moxifloxacin

              moxifloxacin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

              moxifloxacin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Ciprofloxacin, norfloxacin, & ofloxacin are most likely to interact w/warfarin; data for other quinolones is conflicting. Monitor INR closely.

            • nabumetone

              warfarin and nabumetone both increase anticoagulation. Modify Therapy/Monitor Closely.

            • naproxen

              warfarin and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • nateglinide

              nateglinide will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • nelfinavir

              nelfinavir will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • neomycin PO

              neomycin PO increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • nettle

              warfarin increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • nevirapine

              nevirapine will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nifedipine

              nifedipine will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              nilotinib will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilutamide

              nilutamide will increase the level or effect of warfarin by decreasing metabolism. Use Caution/Monitor.

            • nintedanib

              nintedanib increases effects of warfarin by anticoagulation. Use Caution/Monitor. Nintedanib is a VEGFR inhibitor, and may increase the risk of bleeding; monitor patients on full anticoagulation therapy; monitor closely for bleeding and adjust therapy as needed .

            • nitisinone

              nitisinone will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

            • obeticholic acid

              obeticholic acid decreases effects of warfarin by unknown mechanism. Modify Therapy/Monitor Closely. Coadministration has been shown to increase S-warfarin exposure by 13%, but lowered INR by 11%. Monitor INR and adjust warfarin dose accordingly.

            • ofloxacin

              ofloxacin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

              ofloxacin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Ciprofloxacin, norfloxacin, & ofloxacin are most likely to interact w/warfarin; data for other quinolones is conflicting. Monitor INR closely.

            • omadacycline

              omadacycline increases toxicity of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir increases toxicity of warfarin by anticoagulation. Use Caution/Monitor. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment; frequent monitoring of INR values recommended during treatment and post-treatment follow-up.

            • omega 3 carboxylic acids

              omega 3 carboxylic acids, warfarin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3 acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

            • omega 3 fatty acids

              omega 3 fatty acids, warfarin. Other (see comment). Use Caution/Monitor. Comment: Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding. Monitor for changes in INR.

            • omeprazole

              omeprazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • oritavancin

              oritavancin will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP2C9 inhibitor; caution if coadministered with CYP2C9 substrates that have a narrow therapeutic index

            • orlistat

              orlistat decreases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Orlistat may decrease vitamin K absorption; patients on chronic stable doses of warfarin who are prescribed orlistat should be monitored closely for changes in coagulation parameters.

            • ospemifene

              warfarin, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

            • oxaprozin

              warfarin and oxaprozin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • panax ginseng

              warfarin and panax ginseng both increase anticoagulation. Modify Therapy/Monitor Closely.

            • parecoxib

              warfarin and parecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.

            • paromomycin

              paromomycin increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • pau d'arco

              warfarin and pau d'arco both increase anticoagulation. Modify Therapy/Monitor Closely.

            • pegaspargase

              pegaspargase increases effects of warfarin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

            • peginterferon alfa 2a

              peginterferon alfa 2a will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b decreases levels of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered. .

            • pentobarbital

              pentobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              pentobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              pentobarbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pentoxifylline

              pentoxifylline increases effects of warfarin by pharmacodynamic synergism. Use Caution/Monitor.

            • phenobarbital

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              warfarin increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.

              phenytoin, warfarin. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time.

            • phytoestrogens

              warfarin and phytoestrogens both increase anticoagulation. Modify Therapy/Monitor Closely.

            • pipemidic acid

              pipemidic acid will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • piroxicam

              warfarin and piroxicam both increase anticoagulation. Modify Therapy/Monitor Closely.

            • pitolisant

              pitolisant will decrease the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.

            • porfimer

              warfarin decreases effects of porfimer by pharmacodynamic antagonism. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prednisolone

              prednisolone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • prednisone

              prednisone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              prednisone, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • primidone

              primidone will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              primidone will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              primidone will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • propafenone

              propafenone increases effects of warfarin by decreasing metabolism. Use Caution/Monitor.

            • propranolol

              propranolol increases levels of warfarin by decreasing metabolism. Use Caution/Monitor. The anticoagulant effect of warfarin may be increased.

            • propylthiouracil

              propylthiouracil decreases effects of warfarin by pharmacodynamic antagonism. Use Caution/Monitor.

            • quinidine

              quinidine increases effects of warfarin by decreasing metabolism. Use Caution/Monitor. Dosage reduction of warfarin may be needed during concurrent administration of quinidine. Monitor INR and adjust the dosage accordingly.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • regorafenib

              regorafenib will increase the level or effect of warfarin by anticoagulation. Use Caution/Monitor. Monitor INR more frequently

            • reishi

              warfarin and reishi both increase anticoagulation. Modify Therapy/Monitor Closely.

            • reteplase

              warfarin and reteplase both increase anticoagulation. Modify Therapy/Monitor Closely.

            • ribociclib

              ribociclib will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin decreases levels of warfarin by increasing metabolism. Use Caution/Monitor.

            • rifampin

              rifampin will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              rifampin will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              rifapentine will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifaximin

              rifaximin decreases effects of warfarin by increasing metabolism. Use Caution/Monitor. May occur in patients with GI disease that increases intestinal permeability (increased systemic absorption of rifaximin).

            • ritonavir

              ritonavir will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rivaroxaban

              rivaroxaban, warfarin. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Avoid concurrent use of rivaroxaban with other anticoagulants due to increased bleeding risk other than during therapeutic transition periods where patients should be observed closely. Monitor for signs/symptoms of blood loss.

            • romidepsin

              romidepsin increases effects of warfarin by unknown mechanism. Use Caution/Monitor. Possible elevation of INR.

            • rosuvastatin

              rosuvastatin increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP1A2 substrates, if clinically indicated. If coadministration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing the dosing frequency of INR monitoring.

            • rufinamide

              rufinamide will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • salicylates (non-asa)

              warfarin and salicylates (non-asa) both increase anticoagulation. Modify Therapy/Monitor Closely.

            • salsalate

              warfarin and salsalate both increase anticoagulation. Modify Therapy/Monitor Closely.

            • sarecycline

              sarecycline increases toxicity of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.

            • sarilumab

              sarilumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

            • saw palmetto

              saw palmetto increases toxicity of warfarin by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

            • schisandra

              schisandra will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              secobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              secobarbital will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • secukinumab

              secukinumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • selumetinib

              warfarin and selumetinib both increase anticoagulation. Modify Therapy/Monitor Closely. An increased risk of bleeding may occur in patients taking a vitamin-K antagonist or an antiplatelet agent with selumetinib. Monitor for bleeding and INR or PT in patients coadministered a vitamin-K antagonist or an antiplatelet agent with selumetinib.

            • Siberian ginseng

              warfarin and Siberian ginseng both increase anticoagulation. Modify Therapy/Monitor Closely.

            • siltuximab

              siltuximab, warfarin. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

            • simvastatin

              simvastatin, warfarin. Either increases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Competition by each drug for CYP3A4-mediated metabolism may result in increased INR and increased risk of rhabdomyolysis.

            • smoking

              smoking will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • sodium zirconium cyclosilicate

              sodium zirconium cyclosilicate will increase the level or effect of warfarin by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Separate administration by at least 2 hr. Medications that are weak acids (eg, warfarin) are more readily absorbed with elevated gastric pH.

            • sofosbuvir

              sofosbuvir increases toxicity of warfarin by anticoagulation. Use Caution/Monitor. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment; frequent monitoring of INR values recommended during treatment and post-treatment follow-up.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir, warfarin. unspecified interaction mechanism. Use Caution/Monitor. Fluctuations in INR reported in patients treated for HCV with direct acting antiviral agents. Close monitoring of INR values recommended during treatment and post-treatment follow-up.

            • spironolactone

              spironolactone decreases effects of warfarin by unknown mechanism. Use Caution/Monitor. Interaction is theorized to result from increased concentration of clotting factors as a result of diuresis.

            • streptomycin

              streptomycin increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • sulfasalazine

              warfarin and sulfasalazine both increase anticoagulation. Modify Therapy/Monitor Closely.

            • sulindac

              warfarin and sulindac both increase anticoagulation. Modify Therapy/Monitor Closely.

            • tamsulosin

              warfarin, tamsulosin. Other (see comment). Use Caution/Monitor. Comment: Manufacturer's prescribing information states limited in vitro and in vivo studies were inconclusive; caution advised.

            • teduglutide

              teduglutide increases levels of warfarin by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

            • teriflunomide

              teriflunomide decreases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. May decrease INR by 25%; monitor and adjust warfarin dose accordingly.

            • ticagrelor

              ticagrelor, warfarin. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Increased risk of bleeding during concomitant use of medications that increase potential for bleeding.

            • ticarcillin

              ticarcillin increases effects of warfarin by Other (see comment). Use Caution/Monitor. Comment: Decr vitamin K-producing intestinal flora may increase INR after a few days.

            • ticlopidine

              ticlopidine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • tigecycline

              tigecycline increases levels of warfarin by decreasing elimination. Use Caution/Monitor. Minimal effect on INR; monitor.

            • tinidazole

              tinidazole will increase the level or effect of warfarin by anticoagulation. Modify Therapy/Monitor Closely. Enhanced anticoagulation effect may result in a prolongation of prothrombin time. Dosage of warfarin and other coumarin agents may need to be adjusted during coadministration and up to 8 days after discontinuation of tinidazole.

            • tipranavir

              tipranavir, warfarin. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Effect on warfarin levels cannot be predicted; monitor INR frequently upon starting tipranavir Tx. Tipranavir may affect coagulation parameters and platelet aggregation; caution when coadministered w/ drugs that inhibit platelet aggregation or coagulation.

            • tobacco use

              tobacco use will decrease the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • tobramycin

              tobramycin increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • tolfenamic acid

              warfarin and tolfenamic acid both increase anticoagulation. Modify Therapy/Monitor Closely.

            • tolmetin

              warfarin and tolmetin both increase anticoagulation. Modify Therapy/Monitor Closely.

            • topiramate

              topiramate will decrease the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • toremifene

              toremifene increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor. When concomitant use of anticoagulants with toremifene citrate is necessary, careful monitoring of the prothrombin time is recommended.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension, warfarin. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.

            • triclofos

              triclofos increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

            • ustekinumab

              ustekinumab, warfarin. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • valproic acid

              valproic acid will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • vemurafenib

              vemurafenib will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Exercise caution and consider additional INR monitoring when vemurafenib is used concomitantly with warfarin.

            • venetoclax

              venetoclax increases effects of warfarin by unknown mechanism. Modify Therapy/Monitor Closely. In a drug-drug interaction study in healthy subjects, administration of a single dose of venetoclax with warfarin resulted in an 18-28% increase in Cmax and AUC of R-warfarin and S-warfarin. Because venetoclax was not dosed to steady state, it is recommended that the INR be monitored closely in patients receiving warfarin. .

            • verapamil

              verapamil will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vorapaxar

              warfarin, vorapaxar. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Coadministration of anticoagulants, antiplatelets, or other drug affecting coagulation should be monitored periodically due to potential increased risk of bleeding.

            • voriconazole

              voriconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              voriconazole will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • vorinostat

              vorinostat increases effects of warfarin by Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Monitor PT and INR carefully.

            • vortioxetine

              warfarin, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.

            • voxilaprevir

              voxilaprevir increases toxicity of warfarin by anticoagulation. Use Caution/Monitor. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment; frequent monitoring of INR values recommended during treatment and post-treatment follow-up.

            • zafirlukast

              zafirlukast will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              zafirlukast will increase the level or effect of warfarin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zileuton

              zileuton will increase the level or effect of warfarin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            Minor (50)

            • acetaminophen IV

              acetaminophen IV increases effects of warfarin by unknown mechanism. Minor/Significance Unknown.

            • acetaminophen rectal

              acetaminophen rectal increases effects of warfarin by unknown mechanism. Minor/Significance Unknown.

            • alprostadil intracavernous/urethral

              alprostadil intracavernous/urethral increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown.

            • amobarbital

              amobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • armodafinil

              armodafinil will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • ascorbic acid

              ascorbic acid decreases effects of warfarin by pharmacodynamic antagonism. Minor/Significance Unknown. Dose >10 g/day vitamin C.

            • butabarbital

              butabarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • ceftaroline

              ceftaroline increases effects of warfarin by Other (see comment). Minor/Significance Unknown. Comment: Cephalosporins with a methylthiotetrazole (MTT) side ring (eg, cefotetan, cefoperazone) are more frequently associated with hypoprothrombinemic activity.

            • chlorella

              chlorella decreases effects of warfarin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical, due to vitamin K content.

            • coenzyme Q10

              coenzyme Q10 decreases effects of warfarin by pharmacodynamic antagonism. Minor/Significance Unknown.

            • colestipol

              colestipol decreases levels of warfarin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • cranberry

              cranberry increases effects of warfarin by unknown mechanism. Minor/Significance Unknown. Theoretical interaction, based on case reports. Cranberry may inhibit cytochrome P450 2C9.

            • demeclocycline

              demeclocycline increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown.

            • dexmethylphenidate

              dexmethylphenidate increases effects of warfarin by decreasing metabolism. Minor/Significance Unknown.

            • dimenhydrinate

              dimenhydrinate increases effects of warfarin by unknown mechanism. Minor/Significance Unknown.

            • doxycycline

              doxycycline increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown.

            • efavirenz

              efavirenz will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • esomeprazole

              esomeprazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • etravirine

              etravirine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • felbamate

              felbamate will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • felodipine

              felodipine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • fluconazole

              fluconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • glyburide

              glyburide increases effects of warfarin by unspecified interaction mechanism. Minor/Significance Unknown.

            • horseradish

              horseradish increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

            • metronidazole topical

              metronidazole topical will increase the level or effect of warfarin by decreasing metabolism. Minor/Significance Unknown. Oral metronidazole potentiates the effect of warfarin; less likely to occur with topical administration because of low absorption

            • metronidazole vaginal

              metronidazole vaginal will increase the level or effect of warfarin by decreasing metabolism. Minor/Significance Unknown. Oral metronidazole potentiates the effect of warfarin; less likely to occur with vaginal administration because of low absorption

            • mineral oil

              mineral oil decreases levels of warfarin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • minocycline

              minocycline increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown.

            • modafinil

              modafinil will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • omeprazole

              omeprazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • oxcarbazepine

              oxcarbazepine will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • oxytetracycline

              oxytetracycline increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • parsley

              parsley increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown. Theoretical interaction.

            • pentobarbital

              pentobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • raloxifene

              raloxifene increases effects of warfarin by plasma protein binding competition. Minor/Significance Unknown.

            • ribavirin

              ribavirin decreases effects of warfarin by unknown mechanism. Minor/Significance Unknown. Case report.

            • rifampin

              rifampin will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • rolapitant

              rolapitant, warfarin. Other (see comment). Minor/Significance Unknown. Comment: Coadministration of IV rolapitant with warfarin did not significantly increase systemic exposure to S-warfarin, the effects on INR and prothrombin time were not studied; monitor INR and prothrombin time and adjust the dosage of warfarin, as needed with concomitant use of rolapitant, to maintain the target INR range.

            • rose hips

              rose hips decreases effects of warfarin by pharmacodynamic antagonism. Minor/Significance Unknown. Dose >10 g/day vitamin C.

            • secobarbital

              secobarbital will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • sucralfate

              sucralfate decreases levels of warfarin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • tetracycline

              tetracycline increases effects of warfarin by pharmacodynamic synergism. Minor/Significance Unknown.

            • verteporfin

              warfarin decreases effects of verteporfin by pharmacodynamic antagonism. Minor/Significance Unknown.

            • vitamin E

              vitamin E, warfarin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Vitamin E at RDA does not change INR in pts. on chronic warfarin therapy; megadoses (~10x RDA) may enhance anticoagulant effects in vitamin K deficient pts.

            • voriconazole

              voriconazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • watercress

              watercress decreases effects of warfarin by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction, due to high vitamin K content of watercress.

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            Adverse Effects

            Frequency Not Defined

            Cholesterol embolus syndrome

            Intraocular hemorrhage

            Abdominal pain

            Flatulence

            Alopecia

            Rash

            Pruritus

            Taste disturbance

            Tissue necrosis

            Headache

            Lethargy

            Dizziness

            Hematuria

            Anemia

            Hepatitis

            Respiratory tract bleeding

            Hypersensitivity reaction

            Hemorrhage

            Blood dyscrasias

            Fever

            "Purple toe" syndrome

            Increased fracture risk with long-term usage

            Calciphylaxis

            Postmarketing Reports

            Acute kidney injury

            Limb ischemia, necrosis, and gangrene in patients with HIT and HITTS

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            Warnings

            Black Box Warnings

            Warfarin sodium can cause major or fatal bleeding; bleeding is more likely to occur during the starting period and with a higher dose (resulting in a higher INR)

            Risk factors for bleeding include high intensity of anticoagulation (INR greater than 4), age 65 years or older, highly variable INRs, history of gastrointestinal bleeding, hypertension, cerebrovascular disease, serious heart disease, anemia, malignancy, trauma, renal insufficiency, concomitant drugs, and long duration of warfarin therapy

            Regular monitoring of INR should be performed on all treated patients; those at high risk of bleeding may benefit from more frequent INR monitoring, careful dose adjustment to desired INR, and a shorter duration of therapy

            Patients should be instructed about prevention measures to minimize the risk of bleeding and to immediately report any signs or symptoms of bleeding to their physician

            Contraindications

            Pregnancy, except in women with mechanical heart valves

            Hemorrhagic tendencies or blood dyscrasias

            Recent or contemplated CNS or eye surgery or traumatic surgery resulting in large open surfaces

            Bleeding tendencies associated with CNS hemorrhage, cerebral aneurysms, dissecting aorta, pericarditis and pericardial effusions, bacterial endocarditis, and active ulceration or overt bleeding of the GI, GU, or respiratory tract

            Threatened abortion, eclampsia, and preeclampsia

            Unsupervised patients with conditions associated with potential high level of noncompliance (eg, dementia, alcoholism, psychosis)

            Spinal puncture and other diagnostic or therapeutic procedures with potential for uncontrollable bleeding

            Major regional or lumbar block anesthesia

            Known hypersensitivity

            Malignant hypertension

            Cautions

            Lower doses may be warranted in the elderly, debilitated patients, malnutrition, CHF, or liver disease

            Elicits no direct effect on an established thrombus, nor does it reverse ischemic tissue damage

            INR >4.0 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding

            Skin necrosis reported with use; caution in patients at risk for hemorrhage, necrosis, or gangrene

            Heparin-induced thrombocytopenia, DVT (may defer warfarin until thrombin generation is controlled and thrombocytopenia has resolved)

            Genetic tests may be warranted to determine best dose for individual patients; variations in CYP2C9 and VKORC1 genes may modify response

            Advise patients receiving warfarin to carry a notice stating that they are undergoing anticoagulant therapy, to alert medical/emergency personnel

            Use caution in patients with acute infection or active TB or conditions that may alter normal GI flora; antibiotics and fever may change response to warfarin

            May release atheromatous plaque emboli; may experience symptoms depending on site of embolization common organs like pancreas, liver, kidneys, and spleen, which may lead to necrosis or death

            Use caution in patients with prolonged vitamin K insufficiencies

            Thyroid disease may increase warfarin responsiveness

            May impair synthesis of coagulation factors in patients with reduced liver function, regardless of etiology, which in turn may lead to increased warfarin sensitivity

            Use caution in lactation

            Calciphylaxis or calcium uremic arteriolopathy has been reported in patients with and without end-stage renal disease; discontinue warfarin and treat calciphylaxis as appropriate; consider alternative anticoagulant therapy

            Maintain consistent intake of vitamin K-containing foods; high vitamin K consumption may decrease warfarin effect

            In patients with altered glomerular integrity or with history of kidney disease, acute kidney injury may occur with therapy, possibly in relation to episodes of excessive anticoagulation and hematuria; more frequent monitoring of anticoagulation is advised in patients with compromised renal function

            Hepatic impairment may impair synthesis of clotting factors and decrease metabolism of warfarin; conduct more frequent monitoring for bleeding

            Contraindicated in any unsupervised patient with senility; conduct more frequent monitoring for bleeding in elderly patients receiving therapy in any situation

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            Pregnancy & Lactation

            Pregnancy

            Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications; estimated background risk of major birth defects and miscarriage for indicated population is unknown

            Exposure during pregnancy causes a recognized pattern of major congenital malformations (warfarin embryopathy and fetotoxicity), fatal fetal hemorrhage, and an increased risk of spontaneous abortion and fetal mortality

            Verify pregnancy status of females of reproductive potential prior to initiating therapy

            Advise females of reproductive potential to use effective contraception during treatment, and for at least 1 month after final dose of warfarin

            Lactation

            Not excreted in breast milk as reported in limited published study (AAP Committee states compatible with nursing); because of potential for serious adverse reactions, including bleeding in breastfed infant, consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy; monitor breastfeeding infants for bruising or bleeding

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Interferes with hepatic synthesis of vitamin K-dependent clotting factors II, VII, IX, and X, as well as proteins C and S; S-warfarin is 4 times more potent than R-warfarin

            Warfarin depletes functional vitamin K reserves, which in turn reduces synthesis of active clotting factors, by competitively inhibiting subunit 1 of the multi-unit vitamin K epoxide reductase complex 1 (VKOR1)

            Absorption

            Onset: 36-48 hr

            Duration: 2-5 days

            Peak plasma time: 1.5-3 days

            Distribution

            Protein bound: 99% (albumin)

            Vd: 0.14 L/kg

            Metabolism

            R-warfarin: Hepatic P450 enzymes CYP1A2, CYP2C19, CYP3A4

            S-warfarin: CYP2C9

            Elimination

            Half-life: 20-60 hr (patient specific)

            Pharmacogenomics

            Metabolized primarily via oxidation in the liver by CYP2C9; exerts its anticoagulant effect by inhibiting the protein VKORC1

            Dose influenced by genetic factors (CYP2C9, VKORC1 genotypes)

            Carriers of CYP2C9*2 and CYP2C9*3 require ~19-33% dose reduction, respectively, per allele compared with persons who carry the *1 allele

            Carriers of the VKORC1 A allele require ~28% dose reduction per allele in their genotype compared with persons who carry none

            Genetic testing laboratories

            • The following companies provide genetic testing for CYP2C9 and VKORC1 variants
            • AutoGenomics (http://www.autogenomics.com)
            • EntroGen (http://www.entrogen.com)
            • Kimball Genetics (http://www.kimballgenetics.com)
            • Nanosphere (http://www.nanosphere.us)
            • Osmetech (http://www.osmetech.com)
            • Specialty Laboratories (http://www.specialtylabs.com)
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            Administration

            IV Incompatibilities

            Solution: D10W, NS (?), LR (?)

            Syringe: Heparin

            Y-site: Aminophylline, NH4Cl (?), bretylium, ceftazidime, dobutamine, ciprofloxacin, cimetidine, esmolol, labetalol, metronidazole, Ringer's, vancomycin (may be compatible at low conc of warfarin), and promazine

            IV Preparation

            Reconstitute in 2.7 mL SWI to obtain 2 mg/mL injectable solution

            Use reconstituted solution within 4 hr; discard unused portion

            IV Administration

            Inject 2 mg/mL solution slowly (over 1-2 min) into a peripheral vein

            IV Storage

            Store at room temp and protect from light

            Do not refrigerate

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Jantoven oral
            -
            2.5 mg tablet
            Jantoven oral
            -
            5 mg tablet
            Jantoven oral
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            10 mg tablet
            Jantoven oral
            -
            7.5 mg tablet
            Jantoven oral
            -
            10 mg tablet
            Jantoven oral
            -
            6 mg tablet
            Jantoven oral
            -
            4 mg tablet
            Jantoven oral
            -
            3 mg tablet
            Jantoven oral
            -
            2 mg tablet
            Jantoven oral
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            1 mg tablet
            warfarin oral
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            7.5 mg tablet
            warfarin oral
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            6 mg tablet
            warfarin oral
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            10 mg tablet
            warfarin oral
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            5 mg tablet
            warfarin oral
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            4 mg tablet
            warfarin oral
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            3 mg tablet
            warfarin oral
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            2.5 mg tablet
            warfarin oral
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            2 mg tablet
            warfarin oral
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            1 mg tablet
            warfarin oral
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            5 mg tablet
            warfarin oral
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            4 mg tablet
            warfarin oral
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            3 mg tablet
            warfarin oral
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            2 mg tablet
            warfarin oral
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            1 mg tablet
            warfarin oral
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            5 mg tablet
            warfarin oral
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            4 mg tablet
            warfarin oral
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            2.5 mg tablet
            warfarin oral
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            2 mg tablet
            warfarin oral
            -
            10 mg tablet
            warfarin oral
            -
            6 mg tablet
            warfarin oral
            -
            7.5 mg tablet
            warfarin oral
            -
            2.5 mg tablet
            warfarin oral
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            2 mg tablet
            warfarin oral
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            1 mg tablet
            warfarin oral
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            3 mg tablet
            warfarin oral
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            1 mg tablet
            warfarin oral
            -
            2.5 mg tablet
            warfarin oral
            -
            7.5 mg tablet
            warfarin oral
            -
            10 mg tablet
            warfarin oral
            -
            7.5 mg tablet
            warfarin oral
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            6 mg tablet
            warfarin oral
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            3 mg tablet
            warfarin oral
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            1 mg tablet
            warfarin oral
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            5 mg tablet
            warfarin oral
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            7.5 mg tablet
            warfarin oral
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            6 mg tablet
            warfarin oral
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            4 mg tablet
            warfarin oral
            -
            2.5 mg tablet
            warfarin oral
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            4 mg tablet
            warfarin oral
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            2 mg tablet
            warfarin oral
            -
            5 mg tablet
            warfarin oral
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            6 mg tablet
            warfarin oral
            -
            10 mg tablet
            warfarin oral
            -
            3 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            warfarin oral

            WARFARIN - ORAL

            (WARF-uh-rin)

            COMMON BRAND NAME(S): Coumadin, Jantoven

            WARNING: Warfarin can cause very serious (possibly fatal) bleeding. This is more likely to occur when you first start taking this medication or if you take too much warfarin.To decrease your risk for bleeding, your doctor or other health care provider will monitor you closely and check your lab results (INR test) to make sure you are not taking too much warfarin. Keep all medical and laboratory appointments. Tell your doctor right away if you notice any signs of serious bleeding. See also Side Effects section.

            USES: This medication is used to treat blood clots (such as in deep vein thrombosis-DVT or pulmonary embolus-PE) and/or to prevent new clots from forming in your body. Preventing harmful blood clots helps to reduce the risk of a stroke or heart attack. Conditions that increase your risk of developing blood clots include a certain type of irregular heart rhythm (atrial fibrillation), heart valve replacement, recent heart attack, and certain surgeries (such as hip/knee replacement).Warfarin is commonly called a "blood thinner," but the more correct term is "anticoagulant." It helps to keep blood flowing smoothly in your body by decreasing the amount of certain substances (clotting proteins) in your blood.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking warfarin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor or other health care professional, usually once a day. It is very important to take it exactly as directed. Do not increase the dose, take it more frequently, or stop using it unless directed by your doctor.Dosage is based on your medical condition, laboratory tests (such as INR), and response to treatment. Your doctor or other health care provider will monitor you closely while you are taking this medication to determine the right dose for you.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.It is important to eat a balanced, consistent diet while taking warfarin. Some foods can affect how warfarin works in your body and may affect your treatment and dose. Avoid sudden large increases or decreases in your intake of foods high in vitamin K (such as broccoli, cauliflower, cabbage, brussels sprouts, kale, spinach, and other green leafy vegetables, liver, green tea, certain vitamin supplements). If you are trying to lose weight, check with your doctor before you try to go on a diet.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

            SIDE EFFECTS: Nausea, loss of appetite, or stomach/abdominal pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.This medication can cause serious bleeding if it affects your blood clotting proteins too much (shown by unusually high INR lab results). Even if your doctor stops your medication, this risk of bleeding can continue for up to a week. Tell your doctor right away if you have any signs of serious bleeding, including: unusual pain/swelling/discomfort, unusual/easy bruising, prolonged bleeding from cuts or gums, persistent/frequent nosebleeds, unusually heavy/prolonged menstrual flow, pink/dark urine, coughing up blood, vomit that is bloody or looks like coffee grounds, severe headache, dizziness/fainting, unusual or persistent tiredness/weakness, bloody/black/tarry stools, chest pain, shortness of breath, difficulty swallowing.Tell your doctor right away if any of these unlikely but serious side effects occur: persistent nausea/vomiting, severe stomach/abdominal pain, yellowing eyes/skin.This drug rarely has caused very serious (possibly fatal) problems if its effects lead to small blood clots (usually at the beginning of treatment). This can lead to severe skin/tissue damage that may require surgery or amputation if left untreated. Patients with certain blood conditions (protein C or S deficiency) may be at greater risk. Get medical help right away if any of these rare but serious side effects occur: painful/red/purplish patches on the skin (such as on the toe, breast, abdomen), signs of kidney problems (such as change in the amount of urine), vision changes, confusion, trouble speaking, weakness on one side of the body.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking warfarin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood disorders (such as anemia, hemophilia), bleeding problems (such as bleeding of the stomach/intestines, bleeding in the brain), blood vessel disorders (such as aneurysms), recent major injury/surgery, kidney disease, liver disease, alcohol use, mental/mood disorders (including memory problems), frequent falls/injuries.It is important that all your doctors and dentists know that you take warfarin. Before having surgery or any medical/dental procedures, tell your doctor or dentist that you are taking this medication and about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Avoid getting injections into the muscles. If you must have an injection into a muscle (for example, a flu shot), it should be given in the arm. This way, it will be easier to check for bleeding and/or apply pressure bandages.This medication may cause stomach bleeding. Daily use of alcohol while using this medicine will increase your risk for stomach bleeding and may also affect how this medication works. Limit alcoholic beverages. Ask your doctor or pharmacist about how much alcohol you may safely drink.If you have not been eating well, if you have an illness or infection that causes fever, vomiting, or diarrhea for more than 2 days, or if you start using any antibiotic medications, contact your doctor or pharmacist right away because these conditions can affect how warfarin works.This medication can cause heavy bleeding. To lower the chance of getting cut, bruised, or injured, use great caution with sharp objects like safety razors and nail cutters. Use an electric razor when shaving and a soft toothbrush when brushing your teeth. Avoid activities such as contact sports. If you fall or injure yourself, especially if you hit your head, call your doctor right away. Your doctor may need to check you.The Food & Drug Administration has stated that generic warfarin products are interchangeable. However, consult your doctor or pharmacist before switching warfarin products. Be careful not to take more than one medication that contains warfarin unless specifically directed by the doctor or health care provider who is monitoring your warfarin treatment.Older adults may be at greater risk for bleeding while using this drug.This medication is not recommended for use during pregnancy because of serious (possibly fatal) harm to an unborn baby. Discuss with your doctor the use of reliable forms of birth control while taking this medication and for 1 month after stopping the medication. If you become pregnant or think you may be pregnant, tell your doctor right away. If you are planning pregnancy, discuss a plan for managing your condition with your doctor before you become pregnant. Your doctor may switch the type of medication you use during pregnancy.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.Very small amounts of this medication may pass into breast milk but is unlikely to harm a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Warfarin interacts with many prescription, nonprescription, vitamin, and herbal products. This includes medications that are applied to the skin or inside the vagina or rectum. The following interactions listed do not contain all possible drug interactions. The interactions with warfarin usually result in an increase or decrease in the "blood-thinning" (anticoagulant) effect. Your doctor or other health care professional should closely monitor you to prevent serious bleeding or clotting problems. While you are taking warfarin, it is very important to tell your doctor or pharmacist of any changes in medications, vitamins, or herbal products that you are taking.Some products that may interact with this drug include: imatinib, marijuana (cannabis), dronabinol, mifepristone.Aspirin, aspirin-like drugs (salicylates), and nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, naproxen, celecoxib) may have effects similar to warfarin. These drugs may increase the risk of bleeding problems if taken during treatment with warfarin. Carefully check all prescription/nonprescription product labels (including drugs applied to the skin such as pain-relieving creams) since the products may contain NSAIDs or salicylates. Talk to your doctor about using a different medication (such as acetaminophen) to treat pain/fever. Low-dose aspirin and related drugs (such as clopidogrel, ticlopidine) should be continued if prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention. Consult your doctor or pharmacist for more details.This medication may interfere with a certain laboratory test to measure theophylline levels, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: bloody/black/tarry stools, pink/dark urine, unusual/prolonged bleeding.

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as INR, complete blood count) must be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

            MISSED DOSE: For the best possible benefit, do not miss any doses. If you do miss a dose and remember on the same day, take it as soon as you remember. If you remember on the next day, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up because this could increase your risk for bleeding. Keep a record of missed doses to give to your doctor or pharmacist. Contact your doctor or pharmacist if you miss 2 or more doses in a row.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

            MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.