A case report describes a patient stable on lacidipine, ramipril, levothyroxine, rosuvastatin, metoprolol and acetylsalicylic acid who developed extreme bradycardia (20-25 bpm) and hypotension (50/20 mmHg) 48 hours after starting HIV post-exposure prophylaxis (tenofovir, emtricitabine, lopinavir/ritonavir).  Lopinavir/ritonavir, lacidipine, ramipril and metoprolol were discontinued. Raltegravir was prescribed on day 4. Lacidipine, ramipril were re-instated on day 7 and metoprolol on day 9.  Blood concentrations were analyzed approximately 12 h after the last dose of tenofovir/emtricitabine and 20 h after the last dose of lopinavir/ritonavir. Lopinavir, ritonavir, tenofovir and emtricitabine plasma concentrations were 8.40 mg/L, 0.29 mg/L, 0.059 mg/L and 0.12 mg/L, respectively. The lopinavir plasma concentration was higher than usual (3 to 7 mg/L); but the measurement was done only 3 days after treatment initiation while 2 weeks are required to see the maximal enzyme inducing effects of ritonavir. Tenofovir and emtricitabine plasma concentrations were in the normal range.  Genetic analysis showed the patient to be an intermediate metaboliser for CYP2D6, a normal metaboliser for CYP3A4 and a low expressor of P-gp. The authors propose that the AV block and the hypotension were primarily associated with co-administration of the lopinavir/ritonavir combination with metoprolol and lacidipine as the patient was asymptomatic while he started antiretroviral therapy, and discontinuation of lopinavir/ritonavir, lacidipine, ramipril and metoprolol, restored normal rhythm, and further, re-introduction of lacidipine, ramipril and metoprolol without lopinavir/ritonavir induced no bradyarrythmia.
Extreme bradycardia due to multiple drug-drug interactions in a patient with HIV post-exposure prophylaxis containing lopinavir-ritonavir. Puech R, Gagnieu M-C, Planus C, et al. Br J Clin Pharmacol, 2011, 71(4): 621-623.