Pulmonary Arterial Hypertension Pregnancy: Use only if clearly necessary — PAH in pregnancy is extremely high risk; treprostinil used under specialist supervision; seek specialist PAH and obstetric advice

Treprostinil

Brand names: Tyvaso, Remodulin, Orenitram

Adult dose

Dose: Inhaled: 18 mcg per breath, 3 breaths 4 times daily increasing to 9 breaths 4 times daily. SC infusion: start 1.25 ng/kg/minute, increase by 1.25 ng/kg/minute weekly

Route: Inhaled (Tyvaso), SC continuous infusion (Remodulin), or oral (Orenitram)

Frequency: 4 times daily (inhaled); continuous infusion (SC); twice or three times daily (oral)

Max: 9 breaths per session 4 times daily (inhaled); individual titration (SC)

Inhaled Tyvaso approved for PAH and ILD-PH (INCREASE trial). SC Remodulin: continuous pump required but avoids central line infection risk of IV epoprostenol. Oral Orenitram: food improves absorption but GI side effects prominent.

Paediatric dose

Dose: Seek specialist opinion N/A/kg

Route: SC or inhaled

Frequency: N/A

Max: N/A

Not established in paediatrics; seek specialist paediatric pulmonary hypertension opinion

Dose adjustments

Renal

SC/oral: dose reduction in renal impairment — treprostinil metabolites renally excreted

Hepatic

Reduce initial dose by 50% in mild-moderate hepatic impairment; avoid in severe hepatic impairment

Paediatric weight-based calculator

Patient weight (kg)

Not established in paediatrics; seek specialist paediatric pulmonary hypertension opinion

Clinical pearls

Mechanism: synthetic prostacyclin analogue — more stable than epoprostenol (half-life 4 hours vs 2–3 minutes); same mechanism as epoprostenol (IP receptor agonism) but allows SC or inhaled delivery without need for central line
INCREASE trial (NEJM 2021): inhaled treprostinil vs placebo in PAH associated with interstitial lung disease (ILD-PH) — significant improvement in 6MWT and WHO functional class; first evidence-based PAH treatment specifically for ILD-PH
SC route advantage: avoids central venous catheter and catheter-related infection risk (major cause of mortality in IV epoprostenol patients); SC site pain is the main limitation
Oral treprostinil (Orenitram): first oral prostacyclin for PAH; significant GI side effects limit uptake; used in stable PAH patients tolerating prostacyclin class
MHRA: Remodulin licensed for PAH (SC and IV); Tyvaso/Brinavess inhaled form being evaluated for UK; oral form licensed in US — check current MHRA status; ESC/ERS guidelines recommend treprostinil as prostacyclin option
ILD-PH treatment: inhaled treprostinil targets the pulmonary circulation preferentially — minimal systemic vasodilation; important as systemic hypotension in ILD-PH can worsen ventilation-perfusion mismatch

Contraindications

Known hypersensitivity to treprostinil or structurally related compounds
Severe hepatic impairment

Side effects

Infusion site pain and reaction (most common with SC route — dose-limiting in some patients; requires site rotation)
Headache (prostacyclin class)
Jaw pain (prostacyclin class)
Flushing and vasodilation
Nausea and diarrhoea
Cough (inhaled route)
Hypotension

Interactions

Antihypertensives and diuretics (additive hypotension)
Anticoagulants and antiplatelets (treprostinil inhibits platelet aggregation — additive bleeding risk)
Gemfibrozil (CYP2C8 inhibitor — increases treprostinil exposure; monitor for side effects)

Monitoring

6-minute walk test (baseline and 3–6 monthly)
WHO functional class
Blood pressure (hypotension monitoring)
SC site inspection (site pain, infection, skin necrosis)
RHC haemodynamics (annually or per specialist)
Platelet count and bleeding symptoms

Reference: BNFc; BNF 90; INCREASE trial NEJM 2021;384(4):325-334; ESC/ERS PAH Guidelines 2022; MHRA SPC Remodulin; NICE TA459. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

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