Interaction between Dofetilide and Dolutegravir
Major
Excretion
| ID | DDInter580 and DDInter582 |
| Interaction | Coadministration with dolutegravir may increase the plasma concentrations of dofetilide. The proposed mechanism is dolutegravir inhibition of renal organic cation transporter (OCT2) and potentially multidrug and toxin extrusion transporter (MATE) 1. Dolutegravir has been shown in vivo to inhibit tubular secretion of creatinine by inhibiting OCT2. In vitro, dolutegravir inhibits both OCT2 and MATE1. Clinically, high plasma levels of dofetilide may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death. |
| Management | Given the risk for serious and/or life-threatening cardiovascular events associated with increased dofetilide plasma levels, concomitant use with dolutegravir is considered contraindicated. |
| References | |
| Alternative for Dofetilide |
C01B
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| Alternative for Dolutegravir |
J05A
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.