lloprost delivered via the BREELIB^TM nebulizer: a review of the clinical evidence for efficacy and safety

Abstract

Inhaled iloprost is a well-established medication to treat pulmonary arterial hypertension (PAH), a serious and potentially fatal disease of the pulmonary resistance vessels. The therapeutic administration of iloprost requires six to nine inhalations per day, due to the short biological half-life of this prostacyclin analogue. The I-NebTM AADTM, introduced in 2006, is the most commonly used nebulizer for delivering iloprost, requiring at least 6.5 min for an inhaled dose of 5 µg. In order to reduce inhalation time, a portable nebulizer based on modern-device technology was developed. The acute safety and tolerability of rapid iloprost inhalation via the BREELIBTM nebulizer was assessed in a four-part clinical trial. In this review, I describe the rationale and features of the new nebulizer, with particular emphasis on the safety and tolerability profile of iloprost inhalation via BREELIBTM observed in the first clinical studies. Meanwhile, the BREELIBTM nebulizer is approved and available for inhaled iloprost therapy combining significantly reduced inhalation time with good tolerability. This new approach will certainly improve patient convenience and compliance, possibly resulting in broader acceptance and improved efficacy of iloprost aerosol therapy in PAH.

Digital Tracking of Physical Activity, Heart Rate, and Inhalation Behavior in Patients With Pulmonary Arterial Hypertension Treated With Inhaled Iloprost: Observational Study (VENTASTEP)

“…To reduce bias, the apps did not provide feedback on physical activity to patients or physicians. A nebulizer (Breelib, Bayer AG) was used to record inhalation behavior [ 13 , 15 , 16 ].…”

“…Iloprost, a prostacyclin-based inhaled therapy for patients with primary pulmonary hypertension (idiopathic pulmonary arterial hypertension) in WHO functional class III, has shown beneficial effects on 6-minute walk distance and WHO functional class in clinical trials [10][11][12]. Iloprost is administered via nebulizers such as the Breelib nebulizer (Vectura Group plc) [13], which automatically saves inhalation information (dates, times, and completeness of inhalations).…”

Pulmonary arterial hypertension: available treatments in the modern era

“…However, despite the improvements in exercise capacity, NYHA FC and clinical deterioration reported with its long-term administration, the use of inhaled iloprost in clinical practice is limited by the high number of daily inhalations (six to nine) and the prolonged inhalation times. Modern vibrating mesh nebulizers, recently developed, could overcome these drawbacks, increasing patient's acceptance and adherence to therapy [15]. 2.…”

Clinical efficacy, safety, tolerability, and survival outcome of long-term inhaled iloprost treatment in the management of pulmonary arterial hypertension: Data from prospective multicenter observational OPTION study

“…The development of pathway-specific targeted drugs has considerably improved the management of PAH by symptom reduction, deceleration of disease progression, and prolonged survival (5)(6)(7). Currently approved PAH-specific medicines address the three principal signaling pathways of pulmonary vasoregulation, including prostacyclin pathway (epoprostenol, iloprost, treprostinil, beraprost, and selexipag), nitric oxide pathway (sildenafil, tadalafil, vardenafil, and riociguat), and endothelin pathway (bosentan, ambrisentan, and macitentan) (2,8).…”

“…Inhaled iloprost has emerged as a major strategy in the treatment of PAH with certain advantages such as few systemic adverse effects, simple delivery, and vasodilation through different cellular mechanisms (15)(16)(17). However, its relatively short half-life necessitating frequent dosing (6-9 times per day) is considered likely to affect adherence (7), in addition to a paucity of clinical evidence regarding its therapeutic effectiveness in the long-term (15,18).…”