Potential interaction between warfarin and health supplements containing vitamin K

Through the vigilance of an astute doctor, HSA was alerted to an adverse event (AE) involving warfarin and a health supplement containing vitamin K. Healthcare professionals are reminded to be aware of this potential interaction and to monitor the intake of vitamin K-containing health supplements for patients on warfarin therapy.

Local adverse event involving a change in the formulation of Centrum Silver^®

In April 2013, HSA received an AE report from a doctor involving a 80-year old patient on long-term warfarin therapy and concurrent use of Centrum Silver^® (Pfizer Pte Ltd). Centrum Silver^® is a vitamin K-containing multivitamin which is targeted for consumers above 50 years old.The patient had been on the same warfarin dose for the past three years with International Normalised Ratio (INR) within the therapeutic range of 2–3. During a routine blood test, the INR was unexpectedly reduced to a sub-therapeutic level of 1, which might increase the risk of cardiovascular events such as stroke and thrombus formation. The doctor ruled out possible causes such as changes in diet and concomitant acute illnesses. There were also no recent changes in the patient's medication. After the doctor re-titrated the patient's warfarin dose, the INR eventually returned to therapeutic levels while the patient continued with the new formula of Centrum Silver^®.

Further investigations revealed that the Centrum Silver^® taken by the patient was a new formulation with an addition of 25mcg of vitamin K₁. Vitamin K₁ was not present in the earlier formulation.The new formulation had been available locally since March 2013 with a different packaging to indicate the change in formulation and carried the cautionary statement for multivitamins containing vitamin K: “Consult a healthcare professional prior to use if you are taking a blood thinner such as warfarin.”

Following this AE report, HSA had worked with the company to issue a Dear Healthcare Professional Letter on 1 July 2013 to highlight the presence of vitamin K in the new formulation of Centrum Silver^®.

Discussion

Small amounts of vitamin K₁ (e.g., 10–25 mcg) contained in multivitamin supplements are generally considered safe in patients undergoing warfarin anticoagulation therapy.¹ However, patients with low vitamin K status could be more susceptible to potential interactions, resulting in oversensitivity of INR response to small changes in vitamin K₁ intake.

Three other case reports with this interaction were reported overseas in patients following initiation or cessation of a daily multivitamin containing 25mcg of vitamin K₁.¹ In one case, a 43-year-old woman on warfarin therapy developed a subcapsular hematoma of the right kidney after discontinuing her multivitamin containing vitamin K₁ 25 mcg without notifying her physician. In another case, a 77-year-old man on warfarin therapy started taking a multivitamin containing 25mcg of vitamin K₁ and developed a sub-therapeutic INR within 2.5 weeks. In a third case, an 80-year-old man's INR dropped to a sub-therapeutic level without any other apparent reason after starting a daily multivitamin containing 25mcg of vitamin K₁ two weeks earlier. Prior to that, he had stable INRs with his usual warfarin dosage.

HSA's advisory

While the amount of vitamin K allowed in health supplements is generally considered safe, healthcare professionals managing patients on warfarin are encouraged to monitor their patients' INRs and counsel them on their vitamin K intake from health supplements and food. In particular, patients should be made aware of the presence of vitamin K in health supplements, and to remain alert to any changes in packaging or formulation as in the case of Centrum Silver®. Healthcare professionals should also advise their patients to inform them before starting, stopping or switching health supplements.

Healthcare professionals are reminded to take into consideration the above when counselling patients on warfarin anticoagulation therapy, and to report any suspected AEs associated with the concurrent use of vitamin K-containing health supplements with warfarin to the Vigilance Branch of HSA.

Reference

1. Ann Pharmacother 2003; 37: 1603-6