Drug Interactions between landiolol and lopinavir / ritonavir

Consumer information for this interaction is not currently available.

MONITOR: Lopinavir in combination with ritonavir has been shown to prolong the PR interval of the electrocardiogram in some patients. Theoretically, coadministration with other agents that prolong the PR interval (e.g., beta blockers, calcium channel blockers, atazanavir, digoxin, lacosamide, mefloquine) may result in additive effects and increased risk of conduction disturbances and atrioventricular block. In a study of 39 healthy adults who were administered lopinavir-ritonavir at a therapeutic dosage of 400 mg-100 mg twice daily and a supratherapeutic dosage of 800 mg-200 mg twice daily, mean changes from baseline in the PR interval ranged from 11.6 to 24.4 msec in the 12 hours postdose on treatment day 3 when exposures were approximately 1.5 and 3-fold higher, respectively, than those observed with recommended once-daily or twice-daily dosages of lopinavir-ritonavir at steady state. After baseline correction, the maximum mean difference from placebo in the PR interval was 24.9 msec for the lower dosage and 31.9 msec for the supratherapeutic dosage. Maximum PR interval observed was 286 msec, and no second- or third-degree heart block occurred. There have been postmarketing reports of asymptomatic prolongation of the PR interval in some patients receiving combination antiretroviral therapy containing lopinavir-ritonavir. Second- and third-degree atrioventricular block have occurred rarely in patients with underlying structural heart disease or preexisting conduction system abnormalities and in patients receiving lopinavir-ritonavir with other drugs known to prolong the PR interval.

MANAGEMENT: Caution is advised if lopinavir-ritonavir is used concomitantly with other agents that prolong the PR interval, particularly those that are metabolized by CYP450 3A4 (e.g., calcium channel blockers) because lopinavir-ritonavir is a potent inhibitor of the isoenzyme. The elderly as well as patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies may be at increased risk for developing cardiac conduction disturbances and atrioventricular block associated with the use of lopinavir-ritonavir. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.