Inhaled pulmonary vasodilators for persistent pulmonary hypertension of the newborn: safety issues relating to drug administration and delivery devices

Figures & data

Table 1 Aerosolized vasodilators used in PPHN: nebulizers and dosing in published studies

Vasodilator	Nebulizer (specifications)	Dosing in PPHN studies
Epoprostenol (Flolan^®)	MiniHEART Lo-Floa Particle size: 2–3 μm^Citation38 Nebulization rate: 8 mL/h	50 ng epoprostenol/kg/min^9
	SPAG-2b MMAD: 1.3 μm^Citation21 Nebulization rate: 12.5–15.0 mL/h	2.5 mg epoprostenol/mL at 6 mL/h (51 ng/kg/min)^Citation17 10 μg epoprostenol/mL at 12 mL/h^Citation20,Citation40
Iloprost (Ventavis^®)	Aeroneb Soloc Particle size: 3.1–3.9 μm^Citation22 Nebulization rate: 0.30 mL/min	10 μg iloprost/3 mL in nebulizer to obtain a dose of 1.2 μg^Citation27
	OMRON CX3d MMAD: 3.8 μm^Citation30 Nebulization rate: 0.25 mL/min	1–2.5 μg iloprost/kg every 2–4 hours^Citation29
	SPAG-2b MMAD: 1.3 μm^Citation21 Nebulization rate: 12.5–15.0 mL/h	20 μg iloprost/kg/d^Citation28
	OPTINEB with baffle platee MMAD: 2.3 μm^Citation33 Nebulization rate not provided (only available for treprostinil [mg/min])	2 μg iloprost/kg^Citation32
Prostaglandin E1 (alprostadil)	MiniHEARTa Particle size: 2–3 μm^Citation38 Nebulization rate: 8 mL/h	25–300 ng iloprost/kg/min (incremental doses)^Citation37

Notes:

a MiniHEART Lo-Flo nebulizer (Westmed, Inc., Tucson, AZ, USA).

b SPAG-2 (ICN Pharmaceuticals, Inc., Costa Mesa, CA, USA).

c Aeroneb Solo System (Aerogen Ltd., Galway, Ireland).

d OMRON CX3 nebulizer (OMRON Healthcare Europe B.V., Hoofddorp, the Netherlands).

e OPTINEB Ultrasonic Nebulizer (NEBU-TEC International, Elsenfeld, Germany) was sold to United Therapeutics Corporation (Silver Spring, MD, USA) and is currently available only for delivery of inhaled treprostinil (Tyvaso Inhalation System); Green Baffle Plate MMAD™ 2.3 μm (NEBU-TEC International).

Abbreviations: MMAD, mean mass aerosol diameter; PPHN, persistent pulmonary hypertension of the newborn; SPAG-2, Small Particle Aerosol Generator-2.

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