OBJECTIVE: To report a single patient case that presented with a probable drug 
interaction between warfarin and 3 methods of hormonal contraceptives, as 
assessed by the Horn Interaction Probability Scale.
CASE SUMMARY: A 33-year-old female patient required long-term anticoagulation 
following an aortic valve replacement. While taking warfarin (38.5 mg weekly), 
she transitioned from a monophasic combined oral contraceptive (ethinyl 
estradiol plus norethindrone) to an implantable progestin-only contraceptive 
(etonogestrel) on the advice of her cardiologist. Nineteen days following 
etonogestrel implant insertion, her international normalized ratio (INR) 
decreased to 1.8 and required a 55.8% warfarin dose increase (resulting dose of 
60 mg weekly). Within 10 months, the patient elected to have the implant removed 
due to vaginal bleeding. Nine days following removal of etonogestrel, she 
experienced a transient INR increase to 6.5. Her INR returned to within goal 
range after her warfarin dose was decreased to 55.5 mg weekly. After using 
barrier methods of contraception for 48 days, she initiated an oral 
progestin-only contraceptive (norethindrone). Further warfarin dose adjustments 
were made, resulting in a weekly warfarin dose of 53.5 mg. Thirty-nine days 
after initiation of oral norethindrone, she elected to discontinue use due to 
vaginal bleeding and no longer uses hormonal contraceptive methods. No further 
adjustments to her warfarin dose were warranted.
DISCUSSION: The increased warfarin requirement observed in this patient may have 
been a result of multiple factors. Based on a literature review, we hypothesize 
that the predominant mechanism of interaction was ethinyl estradiol inhibition 
of CYP1A2 and 2C19.
CONCLUSIONS: We recommend that further in vivo studies be completed to 
definitively identify the mechanism of the interaction. It is necessary to 
intensify warfarin monitoring upon initiation or alteration of hormonal 
contraceptives.