Interactions that may enhance the effect of warfarin

• The following interactions may enhance the effect of warfarin, and are likely to need close monitoring and clinical intervention, especially when initiating, changing, and stopping concomitant treatment.
• Alcohol — the person should avoid binge drinking. Heavy drinkers or people with liver disease should avoid alcohol or should not take warfarin.
• Amiodarone — from amiodarone loading onwards, a pragmatic approach is to reduce the warfarin dose by 50%, monitor weekly, and tailor the dose to achieve the target international normalized ratio (INR). This interaction persists for a month or more after amiodarone is withdrawn.
• Antidepressants — selective serotonin reuptake inhibitors (SSRIs) and venlafaxine should be avoided where possible, because of their antiplatelet effect. Duloxetine should also be avoided because it works in a similar way to venlafaxine. Tricyclic antidepressants and mirtazapine should also be avoided due to an enhanced anticoagulant effect. Consider offering trazodone instead.
• 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) — the warfarin dosage should be reduced as necessary. Monitoring is also recommended in people using intravaginal or topical miconazole.
• Clopidogrel or dipyridamole — should be avoided, unless it is clinically recommended.
• Corticosteroids (for example, high-dose prednisolone) — the warfarin dosage should be reduced as necessary.
• Co-trimoxazole — consider whether trimethoprim can be used instead, or reduce warfarin dosage.
• Cranberry juice or cranberry-containing products — the person should avoid cranberry juice and products unless the health benefits outweigh any risks.
• Fibrates — should be avoided if possible, or reduce warfarin dosage by one third to one half.
• Glucosamine — should be avoided.
• Metronidazole — the warfarin dosage should be reduced as necessary.
• Nonsteroidal anti-inflammatory drugs (including topical formulations) — should be avoided, or warfarin reduced as necessary.
• Tamoxifen — should be avoided if possible, or reduce warfarin dosage by one half to two thirds.
• Thyroxine — the warfarin dosage should be reduced as necessary. Consider weekly monitoring whilst the thyroxine dose is being titrated.

Interactions that may reduce the effect of warfarin

• The following interactions may reduce the effect of warfarin, and are likely to need close monitoring and clinical intervention, especially when initiating, changing, and stopping concomitant treatment.
• Tricyclic antidepressants — avoid; they can enhance or reduce the anticoagulant effect. Consider offering trazodone instead.
• 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.
• Carbamazepine — the warfarin dosage may need to be doubled if its anticoagulant effect is markedly reduced.
• Griseofulvin — the warfarin dosage should be increased as necessary.
• Oral contraceptives — the warfarin dosage should be increased as necessary. The INR should also be monitored after emergency oral contraception.
• 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 between 30 to 60% are likely to be needed.
• Phenytoin — the warfarin dosage should be increased as necessary. After stopping phenytoin, the INR may continue to be affected for up to 6 weeks.
• 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.
• Vitamin K-containing vitamin complexes, mineral supplements, and green vegetables (as well as over-the-counter chilblain products) — the warfarin dosage should be increased, or the intake of vitamin K reduced. Vitamin K-rich diets should not be changed without at the same time reducing the warfarin dosage, because excessive anticoagulation and bleeding may occur.
• In addition, it is also be prudent to monitor the INR when warfarin is used concomitantly with the following drugs, especially in older people, as interactions have been documented:
• Allopurinol.
• Azathioprine.
• Grapefruit juice (it may be easier to completely avoid this).
• Influenza vaccine.
• Methylphenidate.
• Orlistat (may reduce the absorption of vitamin K).
• Paracetamol or paracetamol-containing products (particularly if prolonged regular use).
• Propafenone.
• Proton pump inhibitors.
• Quinolone antibiotics.
• Macrolide antibiotics.
• Statins (particularly fluvastatin or rosuvastatin; not pravastatin).
• Stopping smoking (it takes about 1 week for enzyme induction due to smoking to wear off).
• Zafirlukast.