Warfarin interactions

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Drugs that may interact with warfarin

Drug name  Recommendation
Allopurinol  
Amiodarone 

During the loading phase check the international normalized ratio (INR) once a week and adjust the dose according to the INR

When the loading phase has been completed check the INR every 2–4 weeks for 1–2 months

Similarly, when stopping amiodarone, the INR should be checked frequently and the dose adjusted as needed

The interaction between warfarin and amiodarone persists for a month or more after amiodarone is withdrawn

Antibiotics

Measure the INR 4-7 days after any antibiotic has been started

It is difficult to predict if the INR will increase or decrease (this will also depend on how ill the person is).

Azathioprine  
Co-trimoxazole Consider whether trimethoprim can be used instead, or reduce warfarin dosage
Metronidazole The warfarin dosage should be reduced as necessary
Macrolide antibiotics  
Quinolone antibiotics  
Antidepressants
Consider offering trazodone instead 
SSRI and SNRIs Avoid where possible because of their antiplatelet effect
Tricyclic antidepressants Avoid due to an enhanced anticoagulant effect
Mirtazipine  Avoid due to an enhanced anticoagulant effect
St John's wort

Stop St John's wort monitor the INR and then adjust the warfarin dosage as necessary

St John's wort can cause a moderate clinical reduction in the anticoagulant effect

Aspirin or aspirin-containing products for example, cold and influenza preparations, and topical salicylates) should be avoided unless they are clinically recommended
Azoles (in particular fluconazole, miconazole, and voriconazole)

Measure the INR 4–7 days after an oral azole has been started and adjust the dose based on the INR.

Monitoring is also recommended in people using intravaginal or topical miconazole.

Miconazole The anticoagulant effect should be carefully monitored and warfarin dose may need to be reduced
Carbamazepine Warfarin dosage may need to be doubled if its anticoagulant effect is markedly reduced
Clopidogrel or dipyridamole Should be avoided, unless it is clinically recommended
Corticosteroids (for example, high-dose prednisolone) Remeasure the INR 4–7 days after starting an oral corticosteroid and adjust the dose of warfarin as needed based on the INR.
Direct acting anti-viral medications for treatment of chronic hepatitis C such as boceprevir (Victrelis); daclatasvir (Daklinza), dasabuvir (Exviera), ombitasvir, paritaprevir, ritonavir (Viekirax), sofosbuvir (Sovaldi), ledipasvir with sofosbuvir (Harvoni) and simeprevir (Olysio).

NR shoIuld be monitored closely and warfarin therapy adjusted if necessary because of possible changes in liver function

Fibrates Avoid if possible or reduce warfarin dosage by one third to one half
Glucosamine Avoid
Influenza vaccine  
Nonsteroidal anti-inflammatory drugs (including topical formulations)

Avoid or reduce warfarin as necessary

If the person must take an oral NSAID measure the INR 4–7 days after starting treatment counsel on the signs of a gastrointestinal bleeding

Paracetamol Long term use can increase the INR
Tamoxifen

Avoid if possible or reduce warfarin dosage by one half to two thirds

Measure the person's INR 1–2 weeks after starting treatment with tamoxifen.

Thyroxine

Warfarin dosage should be reduced as necessary

Consider weekly monitoring whilst the thyroxine dose is being titrated.

Griseofulvin Warfarin dosage should be increased as necessary.

Rifampicin

A marked reduction occurs within 5 to 7 days of starting rifampicin persisting for up to 5 weeks after the rifampicin is stopped

The warfarin dosage may need to be at least doubled.

   
Methylphenidate  
Orlistat

May reduce the absorption of vitamin K

Paracetamol or paracetamol-containing products

Particularly if prolonged regular use

Phenobarbital or primidone

A reduced effect may be seen within 2 to 4 days (maximum effect by about 3 weeks) after starting phenobarbital and persisting for up to 6 weeks after phenobarbital is stopped

Monitor INR until stable

Dose increases of 30 to 60% are likely to be needed.

 Phenytoin  

Warfarin dosage should be increased as necessary

After stopping phenytoin the INR may continue to be affected for up to 6 weeks

Propafenone  
Proton pump inhibitors  
Statins (particularly fluvastatin or rosuvastatin; not pravastatin)  
Zafirlukast  

Supplements that may interact with warfarin

Supplement Recommendation
Coenzyme Q10 (ubidecarenone)
A controlled study found no interaction.
Reduced warfarin effects have been reported in four cases and increased effects have been reported in others.
Advise the patient or consider some monitoring or both
Danshen (Salvia miltorrhiza)

There have been three cases of markedly increased INRs and bleeding, and one animal study suggests increased warfarin bioavailability. Danshen may have some antiplatelet effects.

Dong quai (Angelica sinensis)
There have been two cases of markedly increased INRs and two experimental studies suggesting a modest increase in prothrombin times with dong quai.
 
Fish oils supplements (containing eicosapentaenoic and docosahexaenoic acids)
Two studies in patients found no interaction (increase in INR or bleeding time), but one study found an increased bleeding time. There is an isolated and unexplained case of raised INR but no bleeding.
High doses of these products increase the risk of bleeding, so some caution is appropriate
Ginger
A controlled study showed no interaction with a ginger supplement, but there are two cases of increased anticoagulant effects with ginger root and ginger tea.
One study described an increase in self-reported bleeding events but INRs were not increased.
Ginkgo biloba
Studies in patients and healthy subjects found no interaction, but there is an isolated and unexplained case of bleeding, and a few cases of bleeding with ginkgo alone.
Ginseng (Panax ginseng or P quinquefolius)
A controlled study using P ginseng found no interaction, whereas two case reports describe reduced anticoagulation. Another controlled study using P quinquefolius found a small reduction in warfarin effects.
 
Glucosamine with or without chondroitin

A number of cases of increased INRs, and one case of decreased INR.

The UK regulatory authority has advised avoidance, but subsequent UK-approved labelling only recommends monitoring.

St John’s wort (Hypericum perforatum)

Stop St John's wort monitor the INR and then adjust the warfarin dosage as necessary

St John's wort can cause a moderate clinical reduction in the anticoagulant effect

Vitamin K (multivitamin dose) Vitamin K is an antidote to warfarin. Small doses (10 to 50µg) in multivitamin supplements are probably unimportant in those with normal vitamin K status, but good monitoring is advisable when starting or stopping the supplement.
Wintergreen (topical methylsalicylate)
Some reports of increased warfarin effects (raised INRs, bleeding) with topical methylsalicylate.

Alcohol and Diet

  •  Alcohol
    • the person should avoid binge drinking. Heavy drinkers or people with liver disease should avoid alcohol or should not take warfarin
    • Vitamin K-rich diets
      • soybean and canola oils and green vegetables such as spinach and broccoli
      • Do not change diet without at the same time reducing the warfarin dosage because excessive anticoagulation and bleeding may occur
    • cranberries or cranberry juice
    • Alcohol
    • Foods and drinks that might interact with warfarin include
    • Garlic
    • Black licorice
    • Grapefruit juice

 

Amiodarone Propafenone Rosuvastatin Metronidazole Rifampicin Phenytoin Warfarin Co-trimoxazole Tamoxifen aspirin Azathioprine Mirtazipine Miconazole Carbamazepine Paracetamol Griseofulvin Methylphenidate Orlistat Phenobarbital primidone fluvastatin pravastatin

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