| Medication | US brand name | Dose/route | Side effects | Comments |
| PDE5 inhibitors |
| Sildenafil | Revatio | Age <1 year: - 0.5 to 1 mg/kg per dose orally 3 times per day
Age ≥1 year: - <20 kg: 10 mg orally 3 times per day
- ≥20 kg: 20 mg orally 3 times per day
Maximum dose: - 20 mg orally 3 times per day
| Headache, flushing, nasal congestion, epistaxis, dizziness, hypotension, peripheral edema, dyspepsia, diarrhea, priapism | - Co-administration of nitrates is contraindicated
- Sensorineural hearing loss and ischemic optic neuropathy have been reported
- In extremely preterm infants, use should be delayed until retinal vascularization established
|
| Tadalafil | Adcirca | Initial dose: - 1 mg/kg/dose orally once daily
Maximum dose: | Similar to sildenafil | - Co-administration of nitrates is contraindicated
- Sensorineural hearing loss has been reported
- Ischemic optic neuropathy has been reported
- Very limited information in children regarding dosing, safety, and efficacy
|
| Calcium channel blockers |
| Nifedipine | | Initial dose: - 0.1 to 0.2 mg/kg per dose orally 3 times per day; increase to 2 to 3 mg/kg/day total oral dose
Maximum dose: Extended release tablets preferred for patients able to swallow whole pills | Hypotension, bradycardia, flushing, headache, peripheral edema, dizziness, rash, gingival hyperplasia | - Contraindicated with RV dysfunction
- Used in patients who demonstrate a response to AVT¶
|
| Amlodipine | | Initial dose: - 0.1 to 0.3 mg/kg per dose orally once daily; may increase to 2.5 to 10 mg orally once daily
Maximum dose: | Similar to nifedipine | - Contraindicated with RV dysfunction
- Used in patients who demonstrate a response to AVT¶
|
| Diltiazem | | Initial dose: - 0.5 mg/kg/dose orally 3 times per day; increase to 2 to 5 mg/kg/day total oral dose
Maximum dose: Extended release formulations preferred for patients able to swallow whole pills | Similar to nifedipine | - Contraindicated with RV dysfunction
- Used in patients who demonstrate a response to AVT¶
|
| Endothelin receptor antagonists |
| Bosentan | Tracleer | Starting dose is one-half maintenance dose; increase to full maintenance after 2 to 4 weeks if LFTs and Hgb are stable Maintenance dose: - <10 kg: 2 mg/kg/dose orally twice per day
- 10 to 20 kg: 31.25 mg orally twice per day
- 20 to 40 kg: 62.5 mg orally twice per day
- >40 kg: 125 mg orally twice per day
Maximum dose: - 125 mg orally twice per day
| 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 LFTs and Hgb and adjust dose per manufacturer's recommendations
- Not recommended in patients with moderate or severe hepatic impairment
- Caution with concomitant use of CYP3A4 inducers and inhibitors
- Is a teratogen; pregnancy test required prior to use and for 1 month afterwards; 2 forms of contraception required
- Concurrent use of bosentan and sildenafil increases bosentan serum levels and decreases sildenafil levels
|
| Ambrisentan | Letairis | Maintenance dose: - <20 kg: 2.5 to 5 mg orally once daily
- >20 kg: 5 to 10 mg orally once daily
Maximum dose: | Peripheral edema, nasal congestion, headache, flushing, anemia, nausea, and decreased sperm count The incidence of serum aminotransferase elevation is low | - Obtain baseline LFTs and Hgb, monitor after 1 month, then every 6 months or as clinically indicated
- Teratogenicity concerns as for bosentan
- Little efficacy and safety data for children; avoid use in neonates and infants
|
| Macitentan | Opsumit | Pediatric dosing is not established Adult dosing: | Nasal congestion, headache, flushing, anemia, decreased sperm count The incidence of serum aminotransferase elevation is low | - Obtain baseline LFTs and Hgb and monitor as clinically indicated
- Teratogenicity as for other ERAs
- Infrequently used in children as there are no available data in pediatric patients
|
| Prostacyclin analogues |
| Epoprostenol (IV) | Flolan Veletri | Initial infusion rate: - 1 to 3 nanograms/kg/min; slowly increase infusion rate over weeks
Maintenance infusion rate: - 50 to 80 nanograms/kg/min, titrated to effect
No clear maximum dose | 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
- Bolus infusion can cause systemic hypotension
- Short elimination half-life (3 to 5 minutes); PH crises can occur rapidly if infusion is stopped
- Cooling is needed for Flolan but not Veletri
- Dose increases needed due to tachyphylaxis
|
| Iloprost (inhaled) | Ventavis | Initial dose: - 2.5 micrograms per inhalation 6 times a day
Maintenance dose: - 5 micrograms per inhalation 6 to 9 times per day
Maximum dose: 45 mcg/day | Cough, wheeze, headache, flushing, jaw pain, diarrhea, rash, hypotension (at higher doses) | - Elimination half-life 20 to 30 minutes
- Potential risk of exacerbating reactive airway disease symptoms
- Patient must be old enough to initiate breath from nebulizer
|
| Treprostinil (IV/SC) | Remodulin | As for epoprostenol, but maintenance infusion rate may need to be higher | As for epoprostenol Pain and redness at SC infusion site | - Stable at room temperature
- Elimination half-life 4 hours
|
| Treprostinil (inhaled) | Tyvaso | Initial dose: - 3 breaths (18 micrograms) 4 times a day
Maintenance dose: - 9 breaths (54 micrograms) 4 times a day
| Cough, headache, nausea, dizziness, flushing, throat irritation | - As for iloprost
- Elimination half-life 4 hours
- Potential risk of exacerbating reactive airway disease symptoms
|
| Treprostinil diolamine (oral) | Orenitram | Initial dose: - 0.125 to 3 times per day, or
- 0.25 mg orally twice per day
Maintenance dose: - Determined by tolerability
| Headache, nausea, diarrhea, jaw pain, extremity pain, hypokalemia, abdominal discomfort, flushing | - Must be taken with food
- Limited experience in pediatric patients
- Unlikely to be sufficient substitute for parenteral prostacyclin for patients requiring high-dose prostacyclin
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