Ambrisentan (Letairis) Side Effects: What to Expect and When to Call Your Doctor

Like all medications, ambrisentan (Letairis) can cause side effects. Understanding what is normal, what to watch for, and when to seek immediate medical help will help you manage your PAH treatment safely and confidently. This guide covers everything from minor expected effects to serious warnings that require urgent action.

Boxed Warning: Risk of Fetal Harm

The most serious risk associated with ambrisentan is its potential to cause serious birth defects. Animal studies consistently showed that ambrisentan is teratogenic — meaning it can cause major malformations in developing fetuses, including abnormalities of the jaw and palate, heart and great vessel malformations, and failure of thyroid and thymus formation. This is why:

Ambrisentan is contraindicated (completely prohibited) during pregnancy

All females of reproductive potential must be enrolled in the Ambrisentan REMS program

Monthly pregnancy tests are required during treatment and for one month after stopping

Two highly effective forms of birth control must be used during treatment and for one month after the last dose

If you become pregnant or think you may be pregnant while taking ambrisentan, contact your doctor immediately. Do not stop the medication on your own without medical guidance.

Common Side Effects of Ambrisentan

These side effects are reported by a significant number of patients and are generally manageable:

Peripheral edema (swelling): Swelling in the ankles, legs, or arms is the most common side effect of ambrisentan and is a known class effect of endothelin receptor antagonists. It is more common when ambrisentan is combined with tadalafil. Inform your doctor if swelling becomes severe or sudden.

Headache: Mild to moderate headaches are common, especially during the initial weeks of treatment. These often improve over time.

Nasal congestion: Stuffy nose or nasal symptoms are reported by some patients.

Flushing: A feeling of warmth or redness in the face is a vasodilatory effect of the medication.

Palpitations: Some patients notice an awareness of their heartbeat. This should be reported to your doctor if new or significantly worsened.

Constipation: Some patients experience slowed bowel movements. Staying hydrated and increasing dietary fiber can help.

Nausea or abdominal discomfort: Taking ambrisentan with food may reduce nausea. Inform your doctor if upper right abdominal pain develops — this could signal liver issues.

Serious Side Effects: When to Call Your Doctor Immediately

These side effects require prompt medical attention:

Signs of liver injury: Nausea, upper right abdominal pain, yellowing of skin or eyes (jaundice), dark urine, clay-colored stools, loss of appetite, or fever. Liver enzyme elevations (ALT, AST) have been reported with ambrisentan. Contact your doctor immediately if these symptoms appear.

Severe or sudden fluid retention: Significant weight gain (more than 2 pounds per day or 5 pounds per week), severe swelling, or difficulty breathing at rest may indicate worsening heart failure or pulmonary edema.

Anemia symptoms: Pale skin, unusual tiredness, shortness of breath at rest, cold hands and feet, or feeling light-headed may indicate a drop in hemoglobin or hematocrit, which has been observed with ambrisentan.

Allergic reaction: Hives, severe itching, swelling of the face, lips, tongue or throat, or difficulty breathing require emergency care. Call 911.

Worsening PAH symptoms: If you notice increasing shortness of breath, significantly reduced exercise capacity, or syncope (fainting), contact your doctor — this may indicate your PAH is worsening or your medication needs adjustment.

Effects on Male Fertility

Animal studies and studies with other endothelin receptor antagonists have shown potential effects on sperm count and sperm quality. Ambrisentan may have an adverse effect on spermatogenesis (sperm production). Men who are concerned about fertility should discuss this with their doctor before starting treatment.

Managing Side Effects

Most patients tolerate ambrisentan reasonably well, and many side effects are manageable with simple adjustments. Never stop ambrisentan abruptly without medical guidance — this can cause rapid worsening of your PAH. If a side effect is troubling you, talk to your doctor about dose adjustments or management strategies before making any changes.

If you are having trouble filling your ambrisentan prescription, medfinder can help you find it at pharmacies near you. For more information on what drugs and substances to avoid while taking ambrisentan, see our guide to ambrisentan drug interactions.