Dofetilide Trimethoprim

Dofetilide See below3 patients must be hospitalized for 3 days during initiation of therapy Cimetidine, hy d roch I o roth iaz i de, ketoconazole, medroxyprogesterone, promethazine, trimethoprim, verapamil (all inhibit dofetilide elimination)... 

Dofetilide has weak affinity for CYP3A4. Concomitant use of dofetilide with cime-tidine, hydrochlorothiazide (including combination products), verapamil, trimethoprim, prochlorperazine, megestrol, or ketoconazole is contraindicated due to significant increases in dofetilide serum concentrations (see Table 8.3). 

Trimethoprim markedly increases the plasma levels of dofetilide. This is likely to be associated with an increased risk of dofetilide-induced QT prolongation and torsade de pointes. 

The manufacturer of dofetilide notes that trimethoprim 160 mg (in combination with sulfamethoxazole 800 mg) twice daily given with dofetilide 500 micrograms twice daily for 4 days increased dofetilide peak levels by 93% and AUC by 103%. Trimethoprim inhibits the active renal tubular secretion mechanism by which dofetilide is eliminated, so reducing its loss from the body (see also Dofetilide + H2-receptor antagonists , p.255). There is a linear relationship between plasma dofetilide concentrations and prolongation of the QT interval, which increases the risk of torsade de pointes arrhythmia. For this reason, the manufacturer contraindicates the use of trimethoprim in patients on dofetilide. This would seem to be a prudent precaution. 

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See also in sourсe #XX -- [ ]

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