Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
CARBAMAZEPINE INTERACTIONS WITH WARFARIN (Coumadin, Jantoven)
THIS IS A VERY POTENT AND POTENTIALLY DANGEROUS COMBINATION. IT MUST BE MONITORED VERY CAREFULLY OR CONTROL OF BOTH ANTICOAGULATION AND SEIZURES CAN BE LOST. YOU COULD HAVE A BLEEDING PROBLEM, A CLOTTING PROBLEM OR SEIZURES, IF THIS IS NOT MANAGED CORRECTLY. STOPPING ONE OF THE DRUGS WITHOUT ADEQUATE SUPERVISION IS ONE OF THE WORST THINGS YOU CAN DO.
WHEN A PERSON IS TAKING warfarin (Coumadin, Jantoven) AND STARTS TAKING CARBAMAZEPINE, THE INR CAN BE EXPECTED TO DROP. IT CAN TAKE ANYWHERE FROM 10 TO 35 DAYS FOR THIS TO HAPPEN. THE INR MUST BE MONITORED FREQUENTLY DURING THIS TIME. AT THE VERY BEGINNING, MONITORING EVERY 3 DAYS IS NECESSARY TO ESTABLISH THAT THE warfarin (Coumadin, Jantoven) LEVEL DOES NOT DROP PRECIPITOUSLY. AFTER THAT, I PREFER TO DO IT ONCE A WEEK SO THAT I GET AN IDEA OF WHAT THE WEEKLY DOSE IS GOING TO BE. WHEN TWO CONSECUTIVE INR VALUES ARE IN THE THERAPEUTIC RANGE, THE INTERVAL BETWEEN MONITORINGS CAN BE INCREASED. TYPICALLY, THE warfarin (Coumadin, Jantoven) DOSE WILL HAVE TO BE RAISED TO DOUBLE WHAT IT WAS BEFORE THE CARBAMAZEPINE WAS ADDED.
IF YOU ARE CURRENTLY TAKING warfarin (Coumadin, Jantoven) AND CARBAMAZEPINE, DO NOT STOP WITHOUT PROPER MONITORING. IF YOU STOP THE CARBAMAZEPINE, YOU HAVE A SERIOUS RISK OF YOUR INR GOING TOO HIGH. THIS CAN TAKE UP TO 6 WEEKS TO OCCUR. THE DOSE OF warfarin (Coumadin, Jantoven) MAY NEED TO BE HALF WHAT IT WAS WHEN TAKING THE COMBINATION. THE INR MUST BE MONITORED FREQUENTLY DURING THIS TIME. WHEN TWO CONSECUTIVE INR VALUES ARE IN THE THERAPEUTIC RANGE, THE INTERVAL BETWEEN MONITORINGS CAN BE INCREASED. ONE PATIENT THAT I MONITORED MADE 13 VISITS OVER 3 MONTHS BEFORE HER INR STABILIZED.
THIS GETS TO BE VERY FRUSTRATING FOR BOTH THE PERSON MONITORING THE warfarin (Coumadin, Jantoven) AND THE PATIENT WHO MUST MAKE MANY RETURN VISITS. FROM WHAT PEOPLE WRITE TO ME, THE BIGGEST MISTAKE THAT THE PERSON MONITORING THE warfarin (Coumadin, Jantoven) MAKES IS TO CHECK THE INR TOO OFTEN AND MAKE DOSAGE CHANGES TOO OFTEN. THE PERSON MONITORING THE warfarin (Coumadin, Jantoven) NEEDS TO REMEMBER HOW warfarin (Coumadin, Jantoven) WORKS. IT TAKES ABOUT THREE DAYS FOR THE INR TO STABILIZE AFTER A DOSAGE CHANGE. CHECKING THE INR EVERY DAY WILL ALWAYS PRESENT A FALSE PICTURE OF THE RESULTS OF THE DOSAGE CHANGE. ONE PERSON WROTE TO ME AND SAID THAT THE PERSON MONITORING THEIR warfarin (Coumadin, Jantoven) HAD PRESCRIBED A DOSE OF 20 MG, 10 MG, 5 MG AND 2 MG ON CONSECUTIVE DAYS. THIS TYPE OF DOSAGE SCHEDULE DEMONSTRATES FRUSTRATION AND WILL LEAD TO MORE FRUSTRATION. THE PERSON MONITORING THE warfarin (Coumadin, Jantoven) NEEDS TO SET A SCHEDULE, STICK WITH IT AND ADJUST THE DOSE ONLY ABOUT ONCE PER WEEK.
To further complicate this, carbamazepine does something unusual. It stimulates its own metabolism. This means that after you take it for a period of time, the amount of carbamazepine in your blood will suddenly decrease. The carbamazepine level will need to be monitored frequently too. I have seen one case where this interaction led to both a gastrointestinal bleed and status epilepticus (continuous uncontrollable seizures). This was brought about by a switch from phenytoin to carbamazepine. Both are listed as causing a reduced INR. However, they do not do this on a one-to-one basis, nor is it possible to just substitute one for the other. It must be very tightly monitored. This is one case where checking the INR every three days would be necessary because you are dealing with two potent drug interactions and medications that have serious consequences. For either of the drugs to be above or below their therapeutic ranges could be disastrous.
In another case, a fifty-nine year old woman with an artificial heart valve was started on both nafcillin and carbamazepine. She was a patient at my clinic prior to this incident and again after the incident. She was taking warfarin (Coumadin, Jantoven) 35 mg/wk before the incident. She developed a bacterial endocarditis and possibly some minor cerebral bleeding. Her warfarin (Coumadin, Jantoven) was held for several days until it was certain that this was resolved. When the culture and sensitivity tests showed that nafcillin was not required, another antibiotic was started. It was at her discharge that she was returned to my care for outpatient warfarin (Coumadin, Jantoven) management. At this point she had only been taking carbamazepine for a few days. It took five months of nearly weekly monitoring but this was managed without a serious outcome. At one point she was using 92 mg of warfarin (Coumadin, Jantoven) weekly to maintain her INR in the same range where 35 mg per week had been sufficient.
It is important to consider that a patient is a dynamic person in a constantly changing environment. In this case the patient had endocarditis, started and stopped nafcillin, started and stopped carbamazepine, started Centrum Silver (vitamin K), stopped Centrum Silver for a few days, and stopped warfarin (Coumadin, Jantoven) temporarily for a breast biopsy.
These are two illustrations of how potent and dangerous drug interactions can be managed successfully with careful monitoring and warfarin (Coumadin, Jantoven) dosage adjustments. When warfarin (Coumadin, Jantoven) doses are changed frequently and the INR is monitored often, the weekly amount of warfarin (Coumadin, Jantoven) intake is the most important factor to consider. Patients are rarely harmed by short periods of time outside the desired range.
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Last updated May 6, 2006