Table 2.

Treatment Options for Pediatric Pulmonary Hypertension

Prostacyclin	Medication	Dose	Side Effects	Consideration
	Mechanism of Action: increases cAMP; pulmonary and systemic vasodilation; inhibition of vascular remodeling; antiplatelet aggregation
	Epoprostenol	Initial infusion rate: 1 – 3 ng/kg/min Maintenance infusion rate: 50 – 80 ng/kg/min	Flushing, headache, nausea, diarrhea, jaw discomfort, rash, hypotension thrombocytopenia	Potential risk of hypotension and bleeding in children receiving concomitant drugs such as anticoagulants, platelet inhibitors, or other vasodilators
	Iloprost	Initial dose: 2.5 μg per inhalation 6 times daily Maintenance dose: 5 μg per inhalation 9 times daily	Cough, wheeze, headache, flushing, jaw pain, diarrhea, rash, hypotension (at higher doses)	Potential risk of exacerbating reactive airway disease
	Treprostinil (IV/SQ)	Initial infusion rate: 1.25 – 2 ng/kg/min Maintenance infusion rate: 50 – 80 ng/kg/min	Flushing, headache, nausea, diarrhea, musculoskeletal discomfort, rash, hypotension, thrombocytopenia, pain at subcutaneous infusion site	Similar to epoprostenol
	Treprostinil (Inhaled)	Initial dose: 3 breaths (18 μg) 4 times daily Maintenance dose: 9 breaths (54 μg) 4 times daily	Cough, headache, nausea, dizziness, flushing, throat irritation	Reactive airway symptoms, hypotension possible at high dose
	Treprostinil (Oral)	Initial dose: 0.25 mg PO BID Maintenance dose: Determined by tolerability	Headache, nausea, diarrhea, jaw pain, extremity pain, hypokalemia, abdominal discomfort, flushing	If BID dosing increment is not tolerated, consider TID dosing
Phosphodiesterase type 5 (PDE-5) Inhibitor	Mechanism of action: inhibits PDE-5; pulmonary vasodilation; inhibition of vascular remodeling
	Sildenafil	Pediatric (oral): Initial dose: 0.5 mg/kg/dose PO TID Maintenance dose: 1 – 2 mg/kg/dose PO TID Adult (oral): 20 mg PO TID Pediatric (IV): Loading Dose 0.4 mg/kg over 3 hours Followed by continuous infusion: 1.6 mg/kg/day	Headache, flushing, rhinitis, dizziness, hypotension, peripheral edema, dyspepsia, diarrhea, myalgia, back pain	Co-administration of nitrates is contraindicated Sensorineural hearing loss has been reported Ischemic optic neuropathy has been reported
	Tadalafil	Pediatric (preliminary studies suggest): 1 mg/kg/dose PO QD Adult: 40 mg PO QD	Similar to sildenafil No significant effect on vision	Co-administration of nitrates is contraindicated Sensorineural hearing loss has been reported Ischemic optic neuropathy has been reported
Endothelin receptor antagonist (ERA)	Mechanism of action: ETA/ETB receptor antagonist, pulmonary vasodilation, inhibition of vascular remodeling
	Bosentan	Pediatric: 2 mg/kg/dose PO BID 10–20 kg: 31.25 mg PO BID 20–40 kg: 62.5 mg PO BID >40 kg: 125 mg PO BID Adult: Initial dose: 62.5 mg PO BID Maintenance dose: 125 mg PO BID	Abdominal pain, vomiting, extremity pain, fatigue, flushing, headache, edema, nasal congestion, anemia, decreased sperm count Potential risk of dose-dependent increases in aminotransaminase levels	Monitor liver enzymes and hemoglobin (required) Not recommended in patients with moderate or severe hepatic impairment Caution with concomitant use of CYP3A4 inducers and inhibitors Teratogenecity * REMS*
	Ambrisentan	Pediatric: < 20 kg: 2.5 – 5 mg PO QD > 20 kg: 5 – 10 mg PO QD Adult: Initial dose: 5 mg PO QD Maintenance dose: 10 mg PO QD	Peripheral edema, nasal congestion, headache, flushing, anemia, nausea and decreased sperm count The incidence of serum aminotransferase elevation is low	Obtain baseline liver enzymes and hemoglobin and monitor as clinically indicated Teratogenecity * REMS*
	Macitentan	10 mg PO QD	Nasal congestion, headache, flushing, anemia, decreased sperm count The incidence of serum aminotransferase elevation is low	Obtain baseline liver enzymes and hemoglobin and monitor as clinically indicated Teratogenicity * REMS*
Soluble Guanylate Cyclase (sGC) Stimulator	Mechanism of action: Stimulate sGC, pulmonary vasodilation, inhibition of vascular remodeling
	Riociguat	Initial dose: 0.5 – 1 mg PO TID Maintenance dose: 2.5 mg PO TID	Headache, dizziness, dyspepsia, nausea, diarrhea, hypotension, vomiting, anemia, gastroesophageal reflux, constipation	Co-administration of nitrates and/or phosphodiesterase-5 inhibitors is contraindicated In growing rats effects on bone formation were observed Teratogenecity * REMS*

^*The FDA Amendments Act of 2007 gave the FDA authority to require Risk Evaluation and Mitigation Strategies (REMS) from manufacturers to ensure the benefits of a drug or biological product outweigh its risks. These medications require REMS due to teratogenicity.

None of these medications are FDA approved for pediatric use. Safety and dosing of these medications is not well established in children. Recommended pediatric dosing is included if available.