What is the management of Opsumit (macitentan)-induced pulmonary infiltrates in patients with Pulmonary Arterial Hypertension (PAH)?

Management of Macitentan (Opsumit)-Induced Pulmonary Infiltrates in PAH

Macitentan (Opsumit) should be discontinued immediately upon confirmation of drug-induced pulmonary infiltrates in patients with Pulmonary Arterial Hypertension (PAH), with prompt transition to alternative PAH-specific therapy. 1

Initial Assessment and Management

When pulmonary infiltrates are detected in a patient taking macitentan:

1. Immediate discontinuation of macitentan 1

2. Provide supplemental oxygen to maintain saturation >90% 1

3. Assess severity of pulmonary involvement:

   • Oxygen saturation
   • Diffusion capacity
   • Presence of hypoxemia
   • Signs of right heart failure

4. Manage right ventricular volume overload with diuretics if present, while monitoring:

   • Serum electrolytes
   • Renal function 1

Alternative PAH-Specific Therapy

Transition to alternative PAH therapy based on WHO Functional Class:

1. First-line options:

   • PDE-5 inhibitors (sildenafil or tadalafil) 1

2. Alternative options (use with caution):

   • Soluble guanylate cyclase stimulators (riociguat)
   • Different endothelin receptor antagonists (ambrisentan or bosentan) 1

3. Consider parenteral prostanoid therapy for severe cases:

   • Continuous IV epoprostenol
   • IV/subcutaneous treprostinil 1

Monitoring and Follow-up

Implement a structured monitoring protocol:

• Weekly clinical assessment during the first month after discontinuation 1
• Serial imaging to document resolution of infiltrates 1
• Regular echocardiography to assess right ventricular function 1
• Track BNP/NT-proBNP levels to monitor disease progression 1
• Monitor for signs of clinical deterioration:
  • Worsening exercise capacity
  • Declining oxygen saturation
  • Increasing symptoms

Special Considerations and Differential Diagnosis

• Consider pulmonary veno-occlusive disease (PVOD) in the differential diagnosis, as it presents with similar radiographic findings 1
• Use vasodilators and prostanoids with caution in suspected PVOD due to risk of pulmonary edema 1
• Ensure effective contraception for women of childbearing potential, as macitentan is contraindicated in pregnancy 1
• Monitor liver function tests regularly when transitioning to other endothelin receptor antagonists, as they can cause hepatotoxicity 1

Prevention and Management of Complications

• Administer immunizations against influenza and pneumococcal pneumonia 1
• Treat respiratory infections promptly 1
• Provide oxygen therapy during air travel if baseline oxygen saturation is <92% 1
• Consider lung transplantation for patients who fail to improve with maximal medical therapy 1

The management approach prioritizes immediate discontinuation of the offending agent while ensuring continued treatment of the underlying PAH condition. While the SERAPHIN trial demonstrated macitentan's efficacy in reducing PAH-related hospitalizations and mortality 2, the development of pulmonary infiltrates necessitates prompt intervention to prevent further deterioration of respiratory function and right heart failure.