Dofetilide

Dolutegravir inhibits OCT2, may increase plasma concentrations of dofetilide, a drug eliminated via OCT2.

Cimetidine 400 mg BID increases dofetilide plasma levels by 58%. Concomitant use is contraindicated.

Dolutegravir inhibits OCT2 and MATE1, increasing dofetilide plasma concentrations. Consider alternatives due to risk of Torsade de Pointes.

Hydrochlorothiazide (HCTZ) Alone or in Combination with Triamterene: (see CONTRAINDICATIONS ) Concomitant use of HCTZ alone or in combination with triamterene is contraindicated.

Itraconazole increases dofetilide concentrations, potentially causing QT prolongation and Torsade de Pointes. Contraindicated during and 2 weeks after itraconazole treatment.

Ketoconazole: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of ketoconazole is contraindicated. Ketoconazole at 400 mg daily (the maximum approved prescription dose) co-administered with dofetilide (500 mcg BID) for 7 days has been shown to increase dofetilide C max by 53% in males and 97% in females, and AUC by 41% in males and 69% in females.

Coadministration of lamotrigine with dofetilide (OCT2 substrate with narrow therapeutic index) is not recommended due to increased plasma levels.

Coadministration with lamotrigine ER is not recommended due to narrow therapeutic index and increased plasma levels via OCT2 inhibition.

Concomitant use is contraindicated due to increased risk of QT prolongation and torsades de pointes.

Additive QT interval prolongation effect anticipated, increasing risk of ventricular arrhythmias.

Trimethoprim Alone or in Combination with Sulfamethoxazole: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of trimethoprim alone or in combination with sulfamethoxazole is contraindicated. Trimethoprim 160 mg in combination with 800 mg sulfamethoxazole co-administered BID with dofetilide (500 mcg BID) for 4 days has been shown to increase dofetilide AUC by 103% and C max by 93%.

Triamterene in combination with HCTZ increases dofetilide AUC by 30%, Cmax by 16%, with pharmacodynamic effects increased by 190% (QTc increase over time). Concomitant use is contraindicated.

Trimethoprim 160 mg BID increases dofetilide AUC by 103% and Cmax by 93%. Concomitant use is contraindicated.

Verapamil increases dofetilide peak plasma levels by 42% and is associated with higher occurrence of Torsade de Pointes. Concomitant use is contraindicated.

Antiarrhythmic with narrow safety margin; subject to CYP3A inhibition by clarithromycin, which may increase concentrations and prolong therapeutic/adverse effects.

Concomitant use with digoxin associated with higher rate of torsades de pointes. Use with caution.

Dolutegravir may increase plasma concentrations of dofetilide via OCT2 or MATE1 inhibition, potentially leading to serious adverse effects.

Dolutegravir inhibits renal OCT2 and MATE1 transporters, which may increase plasma concentrations of dofetilide.

Should be avoided due to risk of QT prolongation and torsades de pointes.

Coadministration of lamotrigine with dofetilide (OCT2 substrate with narrow therapeutic index) is not recommended.

Class III antiarrhythmic that prolongs QT interval; should be avoided with toremifene citrate or requires close monitoring.

COSELA inhibits OCT2 and may increase dofetilide concentration, causing serious ventricular arrhythmias and QT interval prolongation including torsade de pointes.

BIC inhibits OCT2 and MATE1, which may increase dofetilide plasma concentrations.

Class III antiarrhythmic drug; specific interaction studies not performed but caution is advised when used with lidocaine and prilocaine.

Tafenoquine may increase dofetilide concentrations through OCT2/MATE transporter inhibition, potentially increasing toxicity risk. Monitor for toxicity and consider dosage reduction.

Tafenoquine may increase dofetilide concentrations via OCT2/MATE transporter inhibition, raising toxicity risk. Monitor for toxicities and consider dosage reduction.

Other Drugs: In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides), and theophylline did not affect the pharmacokinetics of dofetilide.

Other Drugs: In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides), and theophylline did not affect the pharmacokinetics of dofetilide.

Inhibitors of this isoenzyme (e.g., macrolide antibiotics, azole antifungal agents, protease inhibitors, serotonin reuptake inhibitors, amiodarone, cannabinoids, diltiazem, grapefruit juice, nefazadone, norfloxacin, quinine, zafirlukast) should be cautiously co-administered with dofetilide as they can potentially increase dofetilide levels.

If a patient requires dofetilide and anti-ulcer therapy, it is suggested that omeprazole, ranitidine, or antacids (aluminum and magnesium hydroxides) be used as alternatives to cimetidine, as these agents have no effect on the pharmacokinetic profile of dofetilide. Other Drugs: In healthy volunteers, amlodipine, phenytoin, glyburide, ranitidine, omeprazole, hormone replacement therapy (a combination of conjugated estrogens and medroxyprogesterone), antacid (aluminum and magnesium hydroxides), and theophylline did not affect the pharmacokinetics of dofetilide.

In addition, studies in healthy volunteers have shown that dofetilide does not affect the pharmacokinetics or pharmacodynamics of warfarin, or the pharmacokinetics of propranolol (40 mg twice daily), phenytoin, theophylline, or oral contraceptives.