Warfarin is one of the most important anticoagulant drugs frequently used in cardiovascular system diseases requiring anticoagulation, and how well it is used directly affects the therapeutic effect and prognosis of patients. In clinical practice, we often encounter patients taking warfarin in combination with other drugs, resulting in elevated INR or subcutaneous petechiae, gingival bleeding, etc. Although these are not serious problems such as cerebral or abdominal bleeding, it should be noted that many drugs can enhance or diminish the effect of warfarin, resulting in insufficient anticoagulation leading to thrombosis or excessive anticoagulation leading to bleeding tendency, so patients taking warfarin in combination with other drugs also need to check INR regularly. A summary of all drugs and foods that may affect the anticoagulant effect of warfarin is provided for your reference. Song Zhigang, Department of Thoracic Surgery, Shanghai Changhai Hospital
I. The main mechanisms of interaction with warfarin
(1) liver metabolism: warfarin metabolism in the body is mainly through the liver cytochrome P450 enzyme system, so the drugs that can inhibit CYP450 activity can slow down the metabolism of warfarin, prolong the half-life and enhance the anticoagulant effect; conversely, drugs that can induce CYP450 activity can weaken the anticoagulant effect of warfarin.
(2) Binding to plasma proteins: Warfarin binds to plasma proteins (mainly albumin) at a rate of 98% to 99%, so drugs and foods with high plasma protein binding can competitively inhibit warfarin binding to plasma proteins, resulting in an increase in free warfarin and enhanced anticoagulant effect.
Second, warfarin and drug interactions
(1) Drugs that enhance the anticoagulant effect of warfarin
(1) Drugs that affect the absorption of vitamin K: broad-spectrum antibiotics.
(2) Drugs with high plasma protein binding rate: aspirin, sulfonamides, etc.
③Drugs that inhibit the activity of hepatic CYP450 enzyme system: macrolide antibiotics, amiodarone, allopurinol, metronidazole, etc.
④Drugs that increase the affinity of warfarin to the receptor: quinidine, thyroxine, etc.
(5) Drugs that interfere with platelet function: aspirin, salicylates, etc.
(2) Drugs that weaken the anticoagulant effect of warfarin
①Drugs that induce the activity of hepatic CYP450 enzyme system: phenobarbital, carbamazepine, sedative-hypnotics, etc.
②Drugs that compete for enzyme proteins: vitamin K, oral contraceptives and estrogen, etc.
Third, the impact of warfarin anticoagulation drugs, herbs and food (for easy to find the drugs in alphabetical order)
1.1 Drugs that enhance the anticoagulant effect of warfarin
A: Agatroban, acarbose, aceclofenac, amitriptyline, amoxapine, azithromycin, aspirin, alteplase, aximethicin, axitumumab, azapamycin, anandamide, amprenavir, aminosalicylic acid, amiloride, omeprazole, olsalazine, oxaprozin;
B: Pertussisone, phenytoin, benzbromarone, phenylephrine, bivalirudin, bicalutamide, piracetam, piroxicam, pirofen, allopurinol, valproic acid, ibuprofen;
D: macrolide antibiotics, danalaparin, danazol, low molecular heparin, dilaudid, dilaudid, demeclocycline, dexipramine, iodoserine, butalbital hydroxy acid, duthiopin (diphenylthioglycine), acetaminophen, doxepin, doxepin, doxycycline;
E: Goose deoxycholic acid, diazoxide, metformin;
F: vardicoxib, felbamate, fenofibrate, fenoprofen, fenofenine, flurbiprofen, fluvastatin, flufenamic acid, fluvoxamine, fluoxymesterone, fluconazole, fluorouracil, flutamide, halothane, flucloxquinan, fluoxetine, cotrimoxazole;
G: interferon, chamomile, heparin, hyperglycemia, testosterone, glibenclamide, gliclazide, glipizide, glimepiride, gepafloxacin;
H: Erythromycin, ciprofloxacin, cyclophosphamide, sulfapyridine, sulfamethoxazole, sulfisoxazole, sulfopiridone, sulfobenzylurea, sulfonylurea hypoglycemic agents, ashwagandha;
J: Gemcitabine, hexoketocine, gatifloxacin, methandrostenolone, methyldopa, methylprednisolone, mevalonate, methimazole, metronidazole, alcohol;
K: caboprofen, capecitabine, clarithromycin, quinidine, quinine, quetiapine;
L: cephalexin, capsaicin, ranitidine, streptokinase, influenza virus vaccine, clobetofen, clopidogrel, clonidine, chlorambucil, clomipramine, clonoxicam, cloxacillin, rofecoxib, roxithromycin, lovastatin;
M: meloxicam, miconazole, minocycline, mitotane, mirexicam, moxifloxacin;
N: Nalidixic acid, naproxen, naproxen, nilumet, nimesulide, urokinase, norfloxacin;
P: paroxetine, methylphenidate, piperacillin, prednisone, propafenone, protriptyline, propranolol;
Q: Zileuton, hydroxymetholone, penicillin, troglitazone, tramadol, trastuzumab, droxixicam, dehydrotestosterone, ethinylestradiol, norethindrone;
R: Ralteplase;
S: Celecoxib, ticlopidine, ticlofenac, saquinavir, sertraline, sulforaphane, diflunisic acid, disulfiram, diclofenac, dicloxacillin, dicoumarin, chloral hydrate, methyl salicylate, stanozolol;
T: Tamoxifen, ticarcillin, tinidap, tenoxicam, ketoconazole, ketorolac, ketoprofen, cefamandole, cefoperazone, cefoperazone/sulbactam, ceftriaxone, cefotetan, cefoxitin, cefazolin, tromethamine, tolmetin, toremifene, tolterodine;
W: Vancomycin, vitamin A, vitamin E;
X: cimetidine, cisapride, simvastatin, neomycin, bromfenac;
Y: Tobacco, sheep digoxin antibody Fab fragment, ofloxacin, oxymetholone, itraconazole, isoxicam, etanercept, etibatide, isoproterenol, isocyclophosphamide, isoniazid, indolophine, indomethacin, dextropropoxyphene, dextrorphan, dextrorphan;
Z: levothyroxine, levamisole, levofloxacin, zomic acid, zotipine.
1.2 Drugs that attenuate the anticoagulant effect of warfarin
A: 6-mercaptopurine, aprepitant, avidin, aminoglycoside antibiotics;
B: phenobarbital, phenytoin, propyzamide, bosentan, butalbital;
C: Corticosteroids;
D: Diazepam;
F: haloperidol, coenzyme Q10;
G: Grumet, Gembabipitol;
H: Hysobitol, cyclosporine, cyclophosphamide;
J: Hexestrol, meprobamate, methylprednisolone, methimazole, polyacetal;
K: carbamazepine, koleleneamine, cortisone;
L: rifapentine, rifampicin, ritonavir, thioglycollate, azathioprine, lorazepam, chlordiazepoxide, clomipramine, clothianidin, chlortenesin, spironolactone;
M: Mesalachine, Maurethizide;
N: Nafcillin;
P: prednisone, paromidone;
Q: ethinylestradiol, norethindrone;
S: Sconobarbital;
T: tibolone;
W: vitamin C (high dose), vitamin K, pentobarbital;
Y: Echovinol, Isopentobarbital;
Z: zalutostat, secbutabarbital;
2.1 Chinese herbs that enhance the anticoagulant effect of warfarin.
Danshen, angelica, ginkgo biloba, yellow lily, cypress, codonopsis, papaya, gorgonzola, dandelion, licorice, fenugreek, clover, chamomile, turmeric, mugwort, two-sided needle, dragon’s tooth, poplar, willow, bitter wood, herbaceous mignonette, hydrangea, anise, arnica flower, ferula, watercress, hepatica fruit, anemone, smoked grass, parsley, passionflower, red clover, sweet carpenter, shamrock, poison lettuce, white buttercup Yarrow, yarrow, dragon’s tooth grass.
2.2 Herbs that reduce the anticoagulant effect of warfarin.
Ginseng, American ginseng, St. John’s wort.
3.1 enhance the anticoagulant effect of warfarin food.
Grapefruit, grapefruit, grapefruit juice, grapefruit juice, mango, fish oil.
3.2 Foods that diminish the anticoagulant effect of warfarin.
Spinach, cabbage, leeks, coriander, lettuce, celery, watercress, carrots, tomatoes, broccoli, cauliflower, cabbage, lettuce, green peppers, peppers, garlic, onions, egg yolks, soybean oil, cod liver oil, seaweed, avocados, animal liver, black tea, green tea.