Supplemental Reading

Birkett DJ. Pharmacokinetics Made Easy. Sydney:

McGraw-Hill, 1998. Rowland M and Tozer TN. Clinical Pharmacokinetics

(3rd ed.). Baltimore:Williams & Wilkins, 1995. Schumacher GE. Therapeutic Drug Monitoring. Norwalk, CT: Appleton & Lange, 1995.

Case Study How Long Until My Warfarin

A 67-year-old woman with atrial arrhythmia has been treated for 3 years with the antiarrhythmic amiodarone 200 mg and the anticoagulant warfarin 10 mg, both daily. The patient began having liver and ocular toxicity due to amiodarone. The physician decided to discontinue amiodarone therapy because of these adverse effects. Upon checkup, a month after discontinuation of amiodarone, the patient's international normalized ratio (INR), a measure of blood clotting, was greatly elevated, placing the patient at risk for bleeding. The physician reduced the dose of warfarin to 7.5 mg daily. The half-life of amiodarone is approximately 35 days. For how long should the physician continue to monitor the INR?

Dose Stabilizes?

Answer: The half-life of amiodarone is 35 days. Approximately five half-lives are required for functionally complete drug elimination. Thus, it will take approximately 6 months (5 half-lives) before the amiodarone is eliminated from the body. Since amiodarone strongly inhibits metabolism of S-warfarin (active enantiomer), it will continue to affect warfarin metabolism for 6 months following discontinuation of amiodarone. Thus, the dose of warfarin will have to be monitored approximately every month and adjusted if necessary. This monthly monitoring should be continued for at least 6 months, until the metabolism of warfarin stabilizes and a constant dose of warfarin can again be maintained.

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