Management of pulmonary vasodilator therapy in patients with pulmonary arterial hypertension during critical illness

Table 1 Recommendations for enteral administration of pulmonary arterial hypertension medications

Drug	Oral suspension available	Intravenous formulation available	Data supporting enteral drug administration
Sildenafil [8]-[10]	Yes	Yes (dosage is 10 mg every 8 hours)	Reports exist where sildenafil tablet was crushed, dissolved in 5 ml sterile water and administered via enteral tube
Tadalafil [11],[12]	No^a	No	No data available. May be reasonable to use extemporaneous preparation of tadalafil suspension for enteral administration
Bosentan [13]-[16]	No^a	No	Institute for Safe Medication Practices does not recommend crushing due to teratogenic properties^b
Ambrisentan [14],[17]	No	No	Institute for Safe Medication Practices: `do not crush medication’ (extended release product with teratogenic properties); do not administer via enteral tube
Macitentan [18]	No	No	Manufacturer recommends that tablets not be split, chewed or crushed; do not administer via enteral tube
Riociguat [19]	No	No	No data available; would not recommend crushing due to teratogenic properties

^aMay be compounded as follows: grind 15 tadalafil 20 mg tablets in a glass mortar, then mix with 30 ml Ora-Plus (Paddock Laboratories, Minneapolis, MN, USA) and 30 ml Ora-Sweet (Paddock Laboratories) to make a final volume of 60 ml. Suspension is stable for at least 91 days when stored in amber plastic bottles at room temperature. ^bMay be compounded as follows: place bosentan tablet in 5 to 25ml water to create a suspension. An appropriate aliquot of the suspension can be used to deliver the prescribed dose. Any remaining suspension should be discarded. Bosentan should not be mixed or dissolved in liquids with a low (acidic) pH (for example, fruit juices) due to poor solubility; the drug is most soluble in solutions with pH >8.5. Women who are or may become pregnant should not handle crushed bosentan.