Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension.

The management of pulmonary arterial hypertension (PAH) has become more complex in recent years because of increased pharmacotherapy options and longer patient survival with increasing numbers of comorbidities. As such, more opportunities exist for drug-drug interactions between PAH-targeted medications and medications potentially used to treat comorbid conditions. In this review, we provide an overview of pharmaceutical metabolism by cytochrome P450 and discuss important drug-drug interactions for the 14 Food and Drug Administration-approved medications for PAH in the nitric oxide (NO), endothelin, and prostacyclin pathways. Among the targets in the NO pathway (sildenafil, tadalafil, and riociguat), important interactions with nitrates, protease inhibitors, and other phosphodiesterase inhibitors can cause profound hypotension. In the endothelin pathway, bosentan is associated with more drug interactions via CYP3A4 inhibition; macitentan and ambrisentan have fewer interactions of note. Although the parenteral therapies in the prostacyclin pathway bypass significant liver metabolism and avoid drug interactions, selexipag and oral treprostinil may exhibit interactions with CYP2C8 inhibitors such as gemfibrozil and clopidogrel, which can raise drug levels. Finally, we provide a framework for identifying potential drug-drug interactions and avoiding errors.

Iron deficiency and pulmonary arterial hypertension.

The purpose of this review article is to provide a comprehensive review of iron deficiency in the setting of pulmonary arterial hypertension (PAH) and to evaluate the utility of iron supplementation in PAH. Iron deficiency is present in 33%-46% of patients with PAH and has been associated with reduced exercise capacity, compromised oxygen handling, deterioration of right ventricular function, and even mortality. Iron homeostasis and the pathophysiology of PAH are highly intertwined, which has inspired the use of iron supplementation in patients with iron deficiency and PAH. A literature search was performed to identify all available evidence on iron supplementation for PAH. Limited evidence has suggested poor oral bioavailability of oral iron dosed three times a day, but newer formulations such as ferrous maltol may provide better absorption and clinical benefit, especially when dosed less frequently, such as every other day. Intravenous (IV) iron has been shown in observational studies to improve outcomes, but the single randomized control trial in patients without anemia has failed to show benefits in any measure of exercise tolerance. Larger randomized control studies on oral iron with good bioavailability or IV iron in patients with anemia are warranted to explore the potential utility of iron supplementation in patients with PAH.