Retrospective evaluation of a possible interaction between warfarin and levofloxacin.
OBJECTIVE
In order to clarify the clinical significance of a suspected drug interaction, we sought to determine if the international normalized ratio (INR) is affected when levofloxacin is administered in patients receiving long-term warfarin therapy.


METHODS
Retrospective cohort study using pharmacy and medical records.


METHODS
Outpatient clinic.


METHODS
Forty-three patients receiving long-term warfarin therapy who subsequently were prescribed either levofloxacin (22 patients) or felodipine (21 controls); felodipine was chosen as it has been shown not to interact with warfarin. Patients in both groups were required to have a documented INR before the start of levofloxacin or felodipine (pre-INR) and either during levofloxacin or felodipine therapy or within 15 days after the drug had been started (post-INR).


RESULTS
Patient demographics were similar between the two treatment groups. The mean +/- SD age of the patients in the levofloxacin and control groups was 59.5 +/- 8.7 and 65.3 +/- 11.5 years, respectively (p=0.07). The mean change between the pre- and post-INR (primary outcome measure) was 0.31 +/- 0.82 (pre-INR 2.46, post-INR 2.76) and 0.21 +/- 0.54 (pre-INR 2.46, post-INR 2.67) in the levofloxacin and felodipine groups, respectively (p=0.65). A post hoc power analysis, based on a sample-derived, weighted standard deviation of 0.68, revealed that the study had 66% power to detect a change of 0.5 in the INR value. The percentage of patients who required a warfarin dosage adjustment based on the post-INR (secondary outcome measure) was 41% (9 of 22 patients) in the levofloxacin group and 33% (7 of 21 patients) in the felodipine group.


CONCLUSIONS
Although our primary analysis did not detect a warfarin-levofloxacin interaction, the potential for such an interaction, especially in idiosyncratic cases, cannot be ruled out. Clinicians should closely monitor INR values when levofloxacin is administered jointly with warfarin.
McCall
Kenneth L
KL
School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106-1712, USA. ken.mccall@ttuhsc.edu
Scott
John C
JC
Anderson
H Glenn
HG
D000368:Aged; D001831:Body Temperature; D003625:Data Collection; D004334:Drug Administration Schedule; D004347:Drug Interactions; D011307:Drug Prescriptions; D004359:Drug Therapy, Combination; D015736:Felodipine / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000706:statistics & numerical data; D064704:Levofloxacin; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010045:Outpatients / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D014859:Warfarin; D064704:Levofloxacin; D015242:Ofloxacin; D015736:Felodipine