Clinical twisters: Interactions impact therapy

January 28, 2008

Pharmacists evaluate potential drug interactions in patient with atrial fibrillation.

A 60-year-old Caucasian man, T.W., spent the night in your hospital's cardiac unit with new-onset atrial fibrillation (AF). His physician prescribed amiodarone 200 mg daily and warfarin 5 mg daily, instructing T.W. to return for follow-up in one month. The medical resident writing T.W.'s discharge orders calls the pharmacy, asking whether gabapentin interacts with these medications. (T.W. takes 600 mg three times daily for neuropathic pain.) Checking T.W.'s chart, you find he also takes metoprolol 50 mg twice daily; sertraline 100 mg, ramipril 10 mg, and rosuvastatin 20 mg (Crestor, AstraZeneca Pharmaceuticals, LP) daily; with trazodone 50 mg at bedtime. How do you respond?

In this scenario, health professionals performing medication reconciliation at hospital discharge should consider: Is warfarin necessary? Using the CHADS2 risk stratification scheme for stroke prevention in patients with AF, this patient has no documented risk factors. His adjusted stroke rate is 1.9, low risk with new-onset AF. Aspirin 325 mg/day as recommended by the American College of Cardiology/American Heart Association might be considered appropriate: mitigating potential for therapeutic misadventure from a severe amiodarone/warfarin drug interaction. Amiodarone and metabolites inhibit both R- and S-warfarin metabolism, with S-warfarin more strongly inhibited. In virtually all patients receiving this combination, this may significantly increase INR, potentially causing serious to fatal hemorrhagic complications. This interaction occurs rapidly and may persist for weeks due to amiodarone's long half-life. The one-month follow-up is too long-given potential for therapeutic misadventure. INR should be checked within days of discharge.

Drug interactions(s) such as amiodarone + metoprolol may increase the likelihood of hypotensive episodes, bradycardia, or cardiac arrest. Amiodarone + trazodone can cause QT prolongation.

Rosuvastatin + warfarin can potentiate warfarin response, prolonging prothrombin time/INR.

Sertaline + warfarin can potentiate warfarin response, prolonging prothrombin time/INR.

Medication reconciliation would also identify therapeutic duplications: amiodarone and metoprolol are antiarrhythmics; sertaline and trazodone are antidepressants; metoprolol and ramipril are antihypertensive agents. Medication reconciliation would cause us to investigate gabapentin dosing-is this an initiating dose? Or has the patient been titrated upward to this dose and interval? What is T.W.'s renal function? Dose and interval are adjusted with renal function.

James Groce, Pharm.D., CACP
Professor, Campbell University School of Pharmacy
Clinical Assistant Professor of Medicine, University of North Carolina School of Medicine
Clinical Pharmacy Specialist-Anticoagulation
Moses H. Cone Memorial Hospital
Greensboro, N.C.