5 Medication Classes That Can Interact with Warfarin

MARCH 30, 2016
Allison Gilchrist, Associate Editor
Warfarin (Coumadin) can reportedly interact with more than 100 different medications from various classes.
Nearly 30 million prescriptions are written annually for the vitamin K antagonist that has been the mainstay anticoagulant treatment for patients with atrial fibrillation and other cardiac arrhythmia conditions.
It is important for patients on warfarin to maintain a consistent level of the drug in their body in order for it to work. However, many products—including prescription drugs, OTC medications, and herbal supplements—can alter the amount of warfarin in the body because of how they are metabolized or broken down.
Pharmacists should make sure that patients taking the following drugs have their international normalized ratio (INR) checked more frequently.
1. SSRIs
Selective serotonin reuptake inhibitors (SSRIs) have been shown to increase bleeding risk in susceptible patients. There is also evidence of an additive increase in bleeding risk when SSRIs are used concurrently with other drugs that can cause bleeding, such as warfarin.
“It does not appear necessary to avoid using SSRIs or other antidepressants in people taking warfarin, but the possibility of increased bleeding risk should be considered when selecting treatment for depression,” John Horn, PharmD, and Philip Hansten, PharmD, previously wrote in Skidki-na-vse. “If an antidepressant is added to warfarin therapy, monitor closely for evidence of bleeding, especially during the first 2 or 3 months of antidepressant therapy, [but] note that antidepressants are not likely to affect the INR in patients on warfarin.”
Specific SSRIs and antidepressants that have been shown to interact with warfarin include citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), fluoxetine (Prozac, Sarafem), and paroxetine (Paxil, Pexeva).
2. Antiplatelets
Patients with atrial fibrillation who also present with acute coronary syndrome are recommended to receive dual antiplatelet therapy with aspirin and a thienopyridine, which is associated with a heightened risk for severe bleeding. Specific antiplatelet agents that could interact with warfarin include aspirin, clopidogrel (Plavix), ticlopidine, and dipyridamole (Aggrenox, Persantine).
“On one hand, the cardiovascular benefit of starting or continuing aspirin in patients already on warfarin outweighs the increased risk of bleeding in patients presenting with an acute coronary syndrome or those with mechanical heart valves or coronary stents,” according to physicians at the Cleveland Clinic. “However, for patients with stable coronary artery disease or at risk of coronary disease, the benefit of adding aspirin is not substantial, and continuing warfarin alone may be the preferred strategy.”
3. Antibiotics
Interactions between antibiotics and warfarin have been shown to increase the risk of gastrointestinal bleeding.
For example, sulfamethoxazole/trimethoprim (Bactrim) heightens anticlotting effects, which in turn increase the risk of dangerous bleeding. Other antibiotics shown to interact with warfarin include fluconazole (Diflucan), azithromycin (Zithromax), and ciprofloxacin.
Additionally, case reports have shown that antibiotics can eliminate some of the beneficial bacteria that produce vitamin K, thereby inhibiting clotting.
Mixing warfarin with nonsteroidal anti-inflammatory drugs can not only increase the risk for serious gastrointestinal bleeding or hemorrhage, but also decrease the cohesive properties of platelets necessary for clot formation.
Specific NSAIDs that can interact with warfarin include celecoxib (Celebrex), diclofenac (Flector, Cambia, Cataflam, Voltaren-XR), naproxen (Aleve, Anaprox, Naprosyn), and mefenamic acid (Ponstel, Treximet, Vimovo).
Pharmacists and prescribers can avoid concomitant NSAID and warfarin use by identifying the reason for NSAID therapy. If a patient requires an antipyretic effect, for instance, then pharmacists can consider acetaminophen as an alternative.
INR should be monitored each week for patients requiring concomitant NSAID and warfarin use.
5. Herbal Supplements
Several herbal products and supplements have been shown to interact with warfarin.
For example, garlic and ginkgo biloba can increase the risk of bleeding when mixed with warfarin, while products like coenzyme Q10, St. John’s wort, and ginseng can decrease the effects of warfarin, thus increasing the risk of blood clots.
Because high doses of vitamin A or vitamin E can increase the effect of anticoagulation, patients should only take the recommended daily doses based on instructions from their health care provider.