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 Patients

Discontinuation of macitentan is the recommended first-line approach for managing macitentan-induced pulmonary infiltrates in patients with pulmonary arterial hypertension (PAH). Patients should be promptly evaluated for alternative PAH therapy options while the infiltrates resolve.

Diagnostic Approach

When pulmonary infiltrates develop in a patient taking macitentan (Opsumit):

1. Confirm drug-induced etiology:

   • High-resolution CT scan to identify characteristic findings:
     • Subpleural thickened septal lines
     • Centrilobular ground-glass opacities
     • Mediastinal lymphadenopathy
   • Rule out other causes:
     • Infection
     • Heart failure
     • Other drug-induced lung disease

2. Assess severity:

   • Oxygen saturation (maintain >90%)
   • Diffusion capacity (DLCO)
   • Presence of hypoxemia (often more severe than in other forms of PAH)
   • Signs of right heart failure

Management Algorithm

Step 1: Immediate Management

• Discontinue macitentan immediately upon confirmation of drug-induced pulmonary infiltrates
• Provide supplemental oxygen to maintain saturation >90% 1
• Consider hospitalization for patients with significant hypoxemia or clinical deterioration

Step 2: Supportive Care

• Diuretics for right ventricular volume overload if present 1
• Close monitoring of serum electrolytes and renal function
• Consider corticosteroids in severe cases with significant respiratory compromise

Step 3: Alternative PAH Therapy

• Transition to alternative PAH-specific therapy based on WHO Functional Class:

For WHO FC II-III patients:

• Consider PDE-5 inhibitor (sildenafil or tadalafil) 1
• Alternative options:
  • Soluble guanylate cyclase stimulator (riociguat) 1
  • Different endothelin receptor antagonist (ERA) with caution (ambrisentan or bosentan) 1

For WHO FC IV or rapidly deteriorating patients:

• Initiate parenteral prostanoid therapy:
  • Continuous IV epoprostenol preferred 1
  • Alternatives: IV/subcutaneous treprostinil 1

Monitoring and Follow-up

• Weekly clinical assessment during the first month after discontinuation
• Monitor oxygen saturation, exercise capacity, and symptoms
• Serial imaging to document resolution of infiltrates
• Regular echocardiography to assess right ventricular function
• BNP/NT-proBNP levels to track disease progression 2

Important Considerations

• Avoid reintroduction of macitentan due to risk of recurrence with potentially more severe manifestations
• Pulmonary veno-occlusive disease (PVOD) should be considered in the differential diagnosis, as it can present with similar radiographic findings and may be exacerbated by PAH therapies 1
• Vasodilators and prostanoids must be used with caution in patients with suspected PVOD due to high risk of pulmonary edema 1

Special Populations

• Pregnancy: Macitentan is contraindicated in pregnancy. Ensure effective contraception for women of childbearing potential 1, 2
• Liver disease: Monitor liver function tests regularly as ERAs can cause hepatotoxicity
• Concomitant medications: Assess for drug interactions that may have contributed to the adverse effect 3

Prognosis and Long-term Management

• Most patients show improvement after discontinuation of the offending agent
• Lung transplantation should be considered for patients who fail to improve with maximal medical therapy 1, 2
• Regular follow-up assessments every 3-6 months are essential to evaluate treatment response 2

Prevention Strategies

• Immunizations against influenza and pneumococcal pneumonia 1, 2
• Prompt treatment of respiratory infections 1
• Oxygen therapy during air travel if baseline oxygen saturation is <92% 1

By promptly discontinuing macitentan and implementing appropriate alternative therapy, most patients with drug-induced pulmonary infiltrates can be effectively managed while maintaining control of their underlying PAH.