Study Details Drug-Drug Interactions within Combination Therapies for PAH
Bosentan may decrease the effectiveness of sildenafil and tadalafil when used together to treat pulmonary arterial hypertension (PAH), according to a recent study.
The study included 125 patients with PAH (84 participants were female, 57% idiopathic/heritable) who were treated with endothelin receptor antagonists and phosphodiesterase type 5 inhibitors with targeted dosage for at least 1 month. Measurements for clinical parameters and plasma drug concentrations were routinely taken.
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Overall, concentrations of sildenafil and tadalafil were the lowest when the drugs were combined with bosentan, compared with concentration levels when the drugs were combined with ambrisentan or macitentan.
Notably, when combined with sildenafil, bosentan concentrations were more than twice the expected amount in 53.8% of patients.
In addition, the researchers found a significant increase in sildenafil concentrations when patients switched from the combination of sildenafil and bosentan to a combination of sildenafil and macitentan.
“Only the combination with macitentan or ambrisentan led to targeted mean [phosphodiesterase type 5] plasma concentrations and should therefore be preferred to combination with bosentan. Sildenafil-bosentan showed the strongest interaction, with low sildenafil and high bosentan concentrations,” the researchers concluded.
“The study was not powered to analyze whether lower [phosphodiesterase type 5] concentrations cause unsatisfying clinical response. However, plasma concentrations within a targeted range are desirable and may become of increasing importance.”
—Melissa Weiss
Reference:
Grüng E, Ohnesorge J, Benjamin N, et al. Plasma drug concentrations in patients with pulmonary arterial hypertension on combincation treatment [published online May 12, 2017]. Respiration. doi:10.1159/000470916.