Drug Interactions Associated With Therapies for Pulmonary Arterial Hypertension

Objective: To evaluate the potential for drug interactions with therapies for pulmonary arterial hypertension (PAH). Treatments include calcium channel blockers, phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists. Data Sources: A systemic literature search (January 1980-December 2021) was performed using PubMed and EBSCO to locate relevant articles. The mesh terms used included each specific medication available as well as "drug interactions." DAILYMED was used for product-specific drug interactions. Study Selection and Data Extraction: The search was conducted to identify drug interactions with PAH treatments. The search was limited to those articles studying human applications with PAH treatments and publications using the English language. Case reports, clinical trials, review articles, treatment guidelines, and package labeling were selected for inclusion. Data Synthesis: Primary literature and package labeling indicate that PAH treatments are subject to pharmacokinetic and pharmacodynamic interactions. The management of PAH is rapidly evolving. As more and more evidence becomes available for the use of combination therapy in PAH, the increasing use of combination therapy increases the risk of drug-drug interactions. Pulmonary arterial hypertension is also associated with other comorbidities that require concomitant pharmacotherapy. Conclusion: The available literature indicates that PAH therapies are associated with clinically significant drug interactions and the potential for subsequent adverse reactions. Clinicians in all practice settings should be mindful that increased awareness of drug interactions with PAH therapy will ensure optimal management and patient safety.