Table 3.
Interacting drugs prescribed concomitantly with warfarin.
| Cases (% of patients) | Concomitant drug (% of interactions) |
Potential adverse effects | Mechanism of interaction |
|---|---|---|---|
| 986 (14) |
NSAID (24) |
Excessive gastrointestinal bleeding in individual patients | Alteration of gastrointestinal mucosa and platelet agregation8,15,46,47 |
| 671 (9) |
Simvastatin (16) |
Potentiation of the anticoagulant effect of warfarin. Interaction has been clinically insignificant in the majority of patients. | Alteration of warfarin metabolism; inhibition of CYP3A4 isoenzyme8,15,31,39 |
| 476 (7) |
Amiodarone (12) |
Potentiation of the anticoagulant effect of warfarin. Interaction occurs in the majority of patients, develops within two weeks, and lasts for a prolonged period. | Alteration of warfarin metabolism; inhibition of CYP isoenzymes8,15,32,33,39,42,43 |
| 338 (5) |
Propafenone (8%) |
Potentiation of the anticoagulant effect of warfarin | Alteration of warfarin metabolism; inhibition of CYP isoenzymes15,34 |
| 310 (4) |
Allopurinol (8) |
Potentiation of the anticoagulant effect of warfarin. Bleeding was described in individual patients. | Alteration of warfarin elimination35 |
| 306 (4) |
Amitriptyline (7) |
The anticoagulant effect of warfarin can both increase and decrease. | Alteration of warfarin metabolism or slow gastrointestinal motility, thereby modulate warfarin absorbtion45 |
| 268 (4) |
Levothyroxine (7) |
Potentiation of the anticoagulant effect of warfarin | Alteration of vitamin K metabolism15,36 |
| 210 (3) |
Tramadol (5) |
Potentiation of the anticoagulant effect of warfarin | Interaction may be related to the CYP2D6 activity48.49 |
| 178 (3) |
Amoxicillin (4) |
Potentiation of the anticoagulant effect of warfarin | Supression of gut microflora, reduced synthesis of vitamin K-dependent clothing factors8,15,50 |
| 120 (2) |
Etoricoxib, Celecoxib (3) |
Gastrointestinal bleeding in individual patients | Possible pharmacokinetic interaction in people with lower CYP2C9 metabolism; displacement of warfarin from protein binding site51,52 |
| 75 (1) |
Carbamazepine (2) |
Decrease of the anticoagulant effect of warfarin in individual patients | Induction of CYP isoenzymes39,44 |
| 65 (<1) |
Norfloxacin, Ciprofloacin (2) |
The anticoagulant effect of warfarin may be unexpectedly potentiated and result in bleeding. | Uncertain- may be supression of vitamin K production53 |
| 48 (<1) |
Fluconazole, Itraconazole (1) |
The effects of warfarin may be potentiated in individual patients. | Inhibition of CYP isoenzymes15,54 |
| 26 (<1) |
Cefuroxime (<1) |
Increased risk of hypoprothrombinaemia and increased risk of bleeding. Concomitant administration with warfarin is contraindicated. | Vitamin K antagonism, platelet inhibition, decreasing the gut microflora15,55,56 |
| 15 (<1) |
Azathioprine (<1) |
Inhibition of the anticoagulant effect of warfarin | Mechanism is unknown- may decrease the anticoagulant response to warfarin57 |
| 10 (<1) |
Acetaminophen (<1) |
The anticoagulant effect may be potentiated with high doses of paracetamol or in case of prolonged use. | Inhibition of enzymes in vitamin K cycle58,59 |
| 5 (<1) |
Testosterone (<1) |
Potentiation of the anticoagulant effect of warfarin. Bleeding might occur. | Mechanism is not understood. Androgens may increase destruction of clotting factors60 |
| 4 (<1) |
Metronidazole (<1) |
Potentiation of the anticoagulant effect of warfarin. Bleeding might occur. | Inhibition of CYP2C9 isoenzyme15,61 |
| 3 (<1) |
Fenofibrate (<1) |
Potentiation of the anticoagulant effect of warfarin. Bleeding might occur. Fatalities have been reported. | Mechanism is uncertain, displacement of warfarin from binding sites, inhibition of CYP2C9 izoenzyme15,62 |
| 2 (<1) |
Ciprofibrate (<1) |
Potentiation of the anticoagulant effect of warfarin. Bleeding might occur. | Mechanism is uncertain, displacement of warfarin from binding sites, inhibition of CYP2C9 izoenzyme15,63 |
| 2 (<1) |
Norgestimate (<1) |
Decrease of the anticoagulant effect of warfarin in individual patients | Mechanism not understood64 |