Prostacyclin Analogue — Pulmonary Arterial Hypertension / Digital Ulcers Pregnancy: Use with caution — limited data; benefit/risk assessment in specialist PAH centre

Treprostinil

Brand names: Remodulin (SC/IV), Tyvaso (inhaled), Orenitram (oral)

Adult dose

Dose: SC infusion: 1.25 ng/kg/min initially, titrate by 1.25 ng/kg/min weekly; IV: same as SC; Inhaled (Tyvaso): 3 breaths (18 mcg) 4x/day; Oral (Orenitram): 0.25 mg BD with food

Route: Subcutaneous infusion, IV infusion, inhalation, or oral

Frequency: Continuous (SC/IV); 4 times daily (inhaled); twice daily (oral)

Max: Titrated individually for SC/IV; inhaled 9 breaths 4x/day; oral titrated to max 16 mg BD

SC route: infused via subcutaneous catheter (abdomen/thigh) — site pain is major issue; rotate sites every 3 days. Longer half-life than epoprostenol (4 hours) — brief interruptions less catastrophic but still avoid. Oral form has lower bioavailability and more GI side effects.

Paediatric dose

Route:

Seek specialist opinion — limited paediatric data

Dose adjustments

Renal

Reduce starting dose in renal impairment — increased exposure

Hepatic

Reduce starting dose — hepatically metabolised; avoid severe impairment

Clinical pearls

SC treprostinil avoids central line complications of IV epoprostenol — key advantage in patients who cannot tolerate central venous access
SC site pain is the major limitation — often managed with topical anaesthetics, site rotation, and dose titration
FREEDOM-C2 and GRIPHON trials support use in PAH combination therapy
Oral treprostinil (Orenitram) — only oral prostacyclin licensed in some countries; unpredictable absorption limits use
Digital ulcer prevention in systemic sclerosis: SC treprostinil used off-label when iloprost insufficient

Contraindications

Hypersensitivity to treprostinil
Severe hepatic impairment (relative)

Side effects

SC site pain and reaction (dose-limiting — up to 85% of patients)
Jaw pain
Headache
Diarrhoea
Nausea
Flushing
Hypotension
Bleeding tendency (antiplatelet effect)

Interactions

Anticoagulants — additive bleeding
Antihypertensives — additive hypotension
CYP2C8 inhibitors (gemfibrozil) — increase treprostinil levels

Monitoring

SC site inspection (infection, necrosis)
Blood pressure
6MWD
FBC (platelet function)
Liver and renal function

Reference: BNFc; BNF 90; FREEDOM-C2 Trial; GRIPHON Trial; ESC/ERS PAH Guidelines 2022; NICE TA325 (Treprostinil). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways