What is the role of inhaled treprostinil (a prostacyclin analogue) in the management of secondary pulmonary hypertension?

From the Guidelines

Inhaled treprostinil is a recommended treatment option for patients with secondary pulmonary hypertension, particularly those who remain symptomatic on stable and appropriate doses of an endothelin receptor antagonist (ERA) or a phosphodiesterase 5 inhibitor (PDE5I), with a suggested initial dose of 3 inhalations (18 mg) every 6 hours, which can be titrated up to 9 inhalations (54 mg) every 6 hours as needed and tolerated 1.

Key Points

• Inhaled treprostinil is an effective treatment for secondary pulmonary hypertension, promoting vasodilation in the pulmonary circulation, reducing pulmonary vascular resistance, and improving cardiac output.
• The recommended starting dose is 3 inhalations (18 mg) every 6 hours, with the possibility of increasing the dose up to 9 inhalations (54 mg) every 6 hours as needed and tolerated.
• Treatment should be initiated under the supervision of a physician experienced in pulmonary hypertension management, with regular follow-up to assess efficacy and adjust dosing as needed.
• Common side effects include cough, headache, throat irritation, nausea, and flushing.
• Inhaled treprostinil works by promoting vasodilation in the pulmonary circulation, reducing pulmonary vascular resistance and improving cardiac output, with a targeted delivery system that minimizes systemic side effects compared to parenteral prostacyclin therapies 1.

Considerations

• Patients should be monitored for clinical improvement in exercise capacity, functional class, and hemodynamic parameters.
• The dose can be increased by 3 inhalations at 1-2 week intervals as tolerated, with a maximum dose of 9 inhalations (54 mg) every 6 hours.
• Inhaled treprostinil is delivered via the Tyvaso Inhalation System, a specialized nebulizer device.
• Treatment should be individualized based on patient response and tolerance, with consideration of combination therapy for patients who fail to improve or deteriorate with first-line treatment 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Pulmonary Arterial Hypertension Treprostinil is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to -pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%)

The FDA drug label does not specifically address the use of inhaled treprostinil in secondary pulmonary hypertension. Secondary pulmonary hypertension is not explicitly mentioned in the provided drug labels. The labels discuss the use of treprostinil in pulmonary arterial hypertension (PAH), which may be primary or secondary, but the specific context of secondary pulmonary hypertension is not directly addressed. Therefore, based on the information provided, no conclusion can be drawn regarding the use of inhaled treprostinil in secondary pulmonary hypertension 2.

From the Research

Inhaled Treprostinil in Secondary Pulmonary Hypertension

• Inhaled treprostinil is a prostacyclin analog used to treat pulmonary arterial hypertension (PAH) and secondary pulmonary hypertension 3, 4.
• The safety and tolerability of inhaled treprostinil have been studied in patients with PAH and secondary pulmonary hypertension, with results showing that it is generally well-tolerated and safe 3.
• Common side effects of inhaled treprostinil include cough, headache, and throat irritation, which often improve over time 3.

Efficacy of Inhaled Treprostinil

• Inhaled treprostinil has been shown to improve exercise capacity and symptoms in patients with PAH and secondary pulmonary hypertension 3, 4.
• The FREEDOM-C2 study found that oral treprostinil, a related medication, did not result in a statistically significant improvement in exercise capacity when added to background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy 5.
• However, other studies have found that inhaled treprostinil can improve symptoms and exercise capacity in patients with PAH and secondary pulmonary hypertension 3, 4.

Comparison with Other Treatments

• Prostacyclin and its analogues, including treprostinil, have been shown to be efficacious in treating pulmonary hypertension, with different modes of application and dosing regimens 6.
• The choice of treatment for pulmonary hypertension depends on various factors, including the severity of the disease, the patient's response to treatment, and the presence of comorbidities 6, 7.
• Inhaled treprostinil is one of several treatment options available for patients with PAH and secondary pulmonary hypertension, and its use should be individualized based on patient needs and response to treatment 3, 4.