Ruixuan Yu Treprostinil Injection

1. Indications and Usage
Pulmonary Arterial Hypertension (PAH):
Treatment of PAH (WHO Group 1) to reduce symptoms associated with exercise.
Target Population: Patients with NYHA Class II–IV symptoms due to idiopathic or heritable PAH, or PAH associated with connective tissue diseases or congenital systemic-to-pulmonary shunts.
2. Dosage and Administration
Route of Administration:
Continuous Subcutaneous (SC) or Intravenous (IV) infusion ONLY.
Recommended Dosage:
Initial Dose: 1.25 ng/kg/min. (Reduce to 0.625 ng/kg/min if the patient cannot tolerate the initial dose).
Titration: Increase by 1.25 ng/kg/min weekly for the first 4 weeks, then by 2.5 ng/kg/min weekly thereafter, based on clinical response and tolerability.
Critical Administration Instructions:
Continuous Infusion: Must be administered continuously via an external infusion pump.
Interruption: Abrupt cessation or significant reduction in dose can lead to rebound PAH symptoms.
IV Preparation: If administered intravenously, must be diluted with Sterile Water for Injection or 0.9% Sodium Chloride.
Backup: Patients must have a backup pump and supplies available at all times.
3. Mechanism of Action
Prostacyclin Mimicry:
Treprostinil is a stable analog of prostacyclin (PGI2), which is produced endogenously by endothelial cells.
Receptor Activation:
It binds to and activates prostacyclin receptors on vascular smooth muscle and platelet cells.
Therapeutic Result: This leads to vasodilation (relaxation of smooth muscle in pulmonary and systemic arteries) and inhibition of platelet aggregation, thereby reducing pulmonary vascular resistance and improving exercise capacity.
4. Safety and Warnings
Rebound Hypertension:
Abrupt withdrawal or rapid dose reduction may cause rebound pulmonary hypertension symptoms (dyspnea, dizziness, asthenia).
Bleeding Risk:
Treprostinil inhibits platelet aggregation and may increase the risk of bleeding, especially in patients taking anticoagulants.
Infusion Site Complications:
SC: Pain and erythema are very common. Severe reactions may require conversion to IV.
IV: Risk of sepsis and thrombotic events at the catheter site.
Hypotension:
As a vasodilator, it may cause systemic hypotension, dizziness, or syncope.
5.Adverse Reactions and Clinical Research
Most Common Adverse Reactions:
Injection Site Pain/Reaction: Extremely common (up to 85% in SC studies).
Systemic: Headache, diarrhea, nausea, rash, jaw pain, and flushing.
Clinical Research Highlights:
Efficacy: In a pivotal 12-week placebo-controlled trial, Treprostinil improved the 6-minute walk distance by a mean of 16 meters compared to placebo.
Dose Correlation: Improvement in exercise capacity was noted to be dose-related.
6.Drug Interactions
Anticoagulants/Antiplatelets:
Use with caution due to additive bleeding risks (e.g., Warfarin, Heparin).
Antihypertensives:
Additive hypotensive effects may occur.
CYP450 Enzymes:
No clinically significant interaction with CYP3A4 substrates. (Note: Primarily metabolized by CYP2C8 in some contexts, but no major dose adjustments are typically required for standard inhibitors).
7.Pharmaceutical Information
Chemical Composition:
Active Ingredient: Treprostinil (Dimesylate).
Appearance: Clear, colorless to slightly yellow solution.
Packaging: Single-use vials (various concentrations).
Storage: Store at 20°C to 25°C (68°F to 77°F).