Can Fetzima (levomilnacipran) cause pulmonary hypertension?

Fetzima (Levomilnacipran) and Pulmonary Hypertension Risk

Fetzima (levomilnacipran) has not been directly associated with pulmonary hypertension, but caution is warranted due to its classification as a serotonergic drug (SNRI) which theoretically could contribute to pulmonary hypertension risk in susceptible individuals.

Mechanism and Risk Assessment

Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor (SNRI) that could potentially interact with serotonin metabolism. This is relevant because:

• Drugs affecting serotonin metabolism have been implicated in the development of pulmonary arterial hypertension (PAH), which is classified as Group 1 PH 1
• The European Society of Cardiology/European Respiratory Society guidelines classify drug and toxin-induced PH as Group 1 PAH 2
• Serotonergic drugs are listed as potential concerns for serious adverse reactions when combined with medications that have MAO inhibition properties 2

Evidence Regarding SNRIs and Pulmonary Hypertension

While there is no direct evidence linking Fetzima specifically to pulmonary hypertension:

• Drugs affecting serotonin pathways have historically been associated with PAH risk, with the strongest associations seen with anorexigens like aminorex, fenfluramine, and dexfenfluramine 2, 1
• Selective serotonin reuptake inhibitors (SSRIs) have been implicated in some cases of PAH development 1
• Levomilnacipran is specifically listed in drug interaction tables as a serotonergic drug that requires monitoring when used with other medications that affect MAO activity 2

Comparison with Known Drug-Induced PAH

The evidence for drug-induced PAH is strongest for:

• Dasatinib (a tyrosine kinase inhibitor), which has been reported to cause largely reversible pulmonary arterial hypertension in approximately 0.45-5% of patients 2
• Anorexigens (appetite suppressants) that increase serotonin release and block serotonin reuptake 2

Monitoring and Management Recommendations

For patients on Fetzima who may be at risk for pulmonary hypertension:

• Be alert to symptoms that might suggest developing PAH:

  • Progressive dyspnea on exertion
  • Fatigue
  • Chest pain
  • Syncope or near-syncope
  • Lower extremity edema

• Consider screening echocardiography in patients with:

  • Multiple risk factors for PAH
  • Unexplained dyspnea while on Fetzima
  • Signs of right heart failure

• Diagnostic approach if PH is suspected:

  • Transthoracic echocardiography is the recommended screening tool 2, 3
  • Right heart catheterization is required for definitive diagnosis 3
  • V/Q scan to rule out chronic thromboembolic PH 2

Clinical Perspective

While the direct association between Fetzima and pulmonary hypertension has not been established in clinical studies, the theoretical risk exists based on its mechanism as an SNRI and the known associations between serotonergic drugs and PAH. The risk appears to be lower than with medications that have established associations with PAH, such as dasatinib or anorexigens.

Key Takeaways

• No direct evidence links Fetzima specifically to pulmonary hypertension
• Theoretical risk exists due to its serotonergic mechanism
• Monitor patients on Fetzima for unexplained dyspnea or signs of right heart failure
• Consider alternative antidepressants in patients with pre-existing pulmonary hypertension or multiple risk factors for PAH
• If pulmonary hypertension develops while on Fetzima, consider discontinuation and referral to a PH specialist