One of the problems with treatment combinations is that some of the therapies can affect the others’ ability to do their work. This appears to be the case when Tracleer (bosentan) is combined with the phosphodiesterase type 5 inhibitors Revatio (sildenafil) or Adcirca (taladafil), researchers said.
The evidence is that concentrations of Revatio and Adcirca in patients’ blood dropped when either was used with Tracleer. The lower concentrations could lead to worse treatment outcomes, the team said.
The study, “Plasma Drug Concentrations in Patients with Pulmonary Arterial Hypertension on Combination Treatment,” was published in the journal Respiration.
PAH is a disease characterized by high blood pressure in the vessels that carry blood to the lungs, causing shortness of breath, dizziness, and fatigue.
Tracleer, Opsumit (macitentan), and Letairis/Volibris (ambrisentan) are endothelin receptor antagonists (ERAs) used to improve PAH patients’ exercise capability. They block endothelin receptors, a protein in blood vessels believed to play a role in the development of PAH. ERAs are used in combination with Revatio or Adcirca as a PAH treatment.
Researchers looked at the interactions between the two types of drugs — ERAs and phosphodiesterase type 5 inhibitors, or PDE-5is — to see if either would diminish the effectiveness of the other. Scientists use the term drug interactions when they talk about one drug’s effect on another when they are used together.
The study included 125 PAH patients, 84 women and 41 men.
Researchers found that Tracleer reduced the blood concentrations of Revatio and Adcirca to levels lower than desired. Revatio had the reverse effect on Tracleer, doubling Tracleer’s concentration in more than half the patients.
Opsumit and ambrisentan also increased blood concentration levels of the PDE-5is they were combined with.
Interestingly, when patients were switched from a combination of Tracleer and Revatio to a combination of Opsumit and Revatio, their blood concentrations of Revatio rose.
“Only the combination with macitentan or ambrisentan led to targeted mean PDE-5i [blood] plasma concentrations and should therefore be preferred to combination with bosentan,” the researchers wrote. “Sildenafil-bosentan showed the strongest interaction, with low sildenafil and high bosentan concentrations.
“The study was not powered to analyze whether lower PDE-5i concentrations cause unsatisfying clinical response,” the team added. “However, plasma concentrations within a targeted range are desirable and may become of increasing importance.”