Generic Name

Nourianz

Brand Names

for inhaled treprostinil (TreoVas), a prostacyclin analog used to treat pulmonary arterial hypertension (PAH).

Mechanism

• Treprostinil is a prostacyclin (IP) receptor agonist.
• Binding to IP receptors on smooth‑muscle cells ↑ intracellular cAMP → vasodilation of pulmonary arterioles.
• Decreases pulmonary vascular resistance (PVR) and right‑ventricular afterload.
• Inhibits platelet aggregation and promotes endothelial cell survival.

Pharmacokinetics

• Formulation: 0.4 µg/mL aerosol in a dual‑jet nebulizer.
• Absorption: Pulmonary delivery → rapid systemic uptake; peak plasma concentrations typically within 15–30 min.
• Distribution: Highly protein‑bound (~90 %); distributes widely, including to the pulmonary circulation.
• Metabolism: primarily oxidative via glutathione S‑transferase; minimal CYP involvement.
• Elimination: Renal (~30 %) and hepatic (~70 %); half‑life ≈ 5–7 h.
• Drug–drug interactions: modest; caution with CYP3A4 inhibitors/inducers can alter clearance.

Indications

• New‑ or refractory‑PAH in adults not adequately controlled with oral/IV prostanoids or endothelin‑receptor antagonists.
• Approved for both women and men; contraindicated in pregnancy (category C).

Contraindications

• Hypersensitivity to treprostinil or any excipient.
• Severe pulmonary disease (e.g., uncontrolled COPD, significant bronchospasm) that may impair pulmonary drug delivery.
• Active uncontrolled infection in the lungs.
• Critical bradyarrhythmias or significant conduction abnormalities.
• Pregnancy and lactation – not recommended.
• Caution in patients with hepatic dysfunction; monitor LFTs.

Dosing

• Initial titration: 1.5 µg/inh 3×/wk (4 days).
• Stepwise increase to 3.0 µg/inh 3×/wk, then 4.5 µg/inh, up to a max of 12 µg/inh 3×/wk over 4–6 weeks.
• Device: 16‑mL cylinder with dual‑jet nebulizer; 30 s inhalation, 5–10 s rest between actuations.
• Monitoring: Adjust dose based on tolerability and clinical response (hemodynamics, BNP levels).

Adverse Effects

Monitoring

• Baseline: Right‑heart catheterization, echocardiogram, BNP, spirometry, CBC, LFTs.
• Follow‑up:
• 4–6 weeks: BP, HR, NPR; repeat right‑heart cath if indicated.
• 3–6 month intervals: BNP, echo, functional class (NYHA).
• Pulmonary function tests and cough assessment as needed.
• Laboratory: Monitor renal/hepatic function every 2–3 months.

Clinical Pearls

• Device‑specific best practices: Verify dry‑cylinder fit; perform a “dry‑run” to ensure the patient’s inhalation technique is proper before drug delivery.
• Cumulative dosing tolerance: Patients often develop early tolerability issues; proactive dose adjustments (e.g., 30‑second breaks) can minimize coughing.
• Interaction with endothelin‑receptor antagonists: Combined use can be synergistic but may increase hypotensive response; titrate carefully.
• Pregnancy & lactation considerations: High‑risk, thus avoid in pregnant women and advise against breastfeeding until cleared.
• Physical exam tip: Look for a “pre‑exhaustion” constellation of right‑ventricular enlargement and increased PVR—key indicators for dose escalation.
• Patient education: Counsel on proper storage (desiccated environment), reconstitution steps, and the importance of nightly dosing for maximum efficacy.

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