CCBs. Four options in this class have shown utility, notably in patients who have had a positive vasoreactivity test (see “How best to approach evaluation and diagnosis?”):
Nifedipine is started at 10 mg tid; target dosage is 20 to 60 mg, bid or tid.
Diltiazem is started at 60 mg bid; target dosage is 120 to 360 mg bid.
Amlodipine is started at 5 mg/d; target dosage is 15 to 30 mg/d.
Felodipine is started at 5 mg/d; target dosage is 15 to 30 mg/d.
Felodipine and amlodipine have longer half-lives than other CCBs and are well tolerated.
ERA.Used as vasodilators are ambrinsentan (starting dosage, 5 mg/d; target dosage, 10 mg/d), macitentan (starting and target dosage, 10 mg/d), and bosentan (starting dosage, 62.5 mg bid; target dosage, 125 mg bid).
Nitric oxide–cyclic guanosine monophosphate enhancers.These are the PDE5 inhibitors sildenafil (starting and target dosages, 20 mg tid) and tadalafil (starting dosage, 20 or 40 mg/d; target dosage, 40 mg/d), and the guanylate cyclase stimulant riociguat (starting dosage, 1 mg tid; target dosage, 2.5 mg tid). All 3 agents enhance production of the potent vasodilator nitric oxide, production of which is impaired in PH.
Prostanoids. Several options are available:
Beraprost sodium. For this oral prostacyclin analogue, starting dosage is 20 μg tid; target dosage is the maximum tolerated dosage (as high as 40 μg tid).
Extended-release beraprost. Starting dosage is 60 μg bid; target dosage is the maximum tolerated dosage (as high as 180 μg bid).
Oral treprostinil. Starting dosage is 0.25 mg bid or 0.125 mg tid; target dosage is the maximum tolerated dosage.
Inhaled iloprost. Starting dosage of this prostacyclin analogue is 2.5 μg, 6 to 9 times per day; target dosage is 5 μg, 6 to 9 times per day.
Inhaled treprostinil. Starting dosage is 18 μg qid; target dosage is 54 to 72 μg qid.
Eproprostenol is administered by continuous IV infusion, at a starting dosage of 2 ng/kg/min; target dosage is determined by tolerability and effectiveness (typically, 30 ng/kg/min).
IV treprostinil. Starting dosage 1.25 ng/kg/min; target dosage is determined by tolerability and effectiveness, with a typical dosage of 60 ng/kg/min.
Combination treatment with the agents listed above is often utilized.
Selexipag. This oral selective nonprostainoid prostacyclin receptor agonist is started at 200 μg bid; target dosage is the maximum tolerated, as high as 1600 μg bid.
