Meta Description
Ambrisentan is a selective endothelin receptor antagonist used for the treatment of Pulmonary Arterial Hypertension (PAH). Learn about its uses, dosage, mechanism of action, benefits, side effects, warnings, and precautions in this complete medical guide.
Introduction
Ambrisentan is an advanced oral medication classified under endothelin receptor antagonists (ERA). It is specially designed to manage Pulmonary Arterial Hypertension (PAH), a serious and progressive disease that causes high blood pressure in the arteries of the lungs. PAH forces the heart to work harder, leading to fatigue, shortness of breath, and heart failure if untreated.
Ambrisentan works by targeting endothelin-1, a protein that causes constriction and scarring of pulmonary blood vessels. By blocking this protein, Ambrisentan reduces pulmonary vascular resistance, allowing smoother blood flow and better oxygen delivery to body tissues.
Medical Indications
Ambrisentan is primarily approved for:
1. Pulmonary Arterial Hypertension (PAH), WHO Group 1
Improves exercise capacity
Delays disease progression
Enhances quality of life
2. Combination Therapy
Can be used with other PAH drugs like phosphodiesterase-5 inhibitors (sildenafil, tadalafil) for better results.
Mechanism of Action
Endothelin-1 is a potent vasoconstrictor (narrows blood vessels).
In PAH patients, endothelin-1 is present in abnormally high levels, leading to pulmonary vessel thickening and increased resistance.
Ambrisentan selectively blocks Endothelin-A receptors, reducing vasoconstriction and preventing vascular remodeling.
This action lowers pulmonary artery pressure, decreases the workload on the right side of the heart, and improves physical activity tolerance.
Pharmacokinetics
Absorption: Rapidly absorbed after oral intake.
Bioavailability: High (works effectively with or without food).
Metabolism: Mainly metabolized in the liver by glucuronidation and oxidation.
Excretion: Eliminated mostly through feces, partly in urine.
Half-life: 9ā15 hours (supports once-daily dosing).
Dosage Guidelines
Starting dose: 5 mg orally once daily.
Maintenance dose: May increase to 10 mg once daily if tolerated.
Special conditions:
With cyclosporine: maximum 5 mg/day.
Children: Not well studied; use only under specialist supervision.
Elderly: No specific dose adjustment but monitor closely.
Clinical Benefits
Improves 6-minute walk distance (a test used in PAH patients).
Delays time to clinical worsening.
Reduces hospitalization due to PAH.
Provides better outcomes when combined with other PAH therapies.
Side Effects
Common (Mild)
Headache
Flushing
Nasal congestion or sinusitis
Swelling (peripheral edema)
Stomach discomfort
Serious (Requires medical attention)
Liver toxicity: Jaundice, nausea, vomiting, dark urine.
Anemia: Fatigue, dizziness, shortness of breath.
Hypotension: Dizziness or fainting due to low blood pressure.
Allergic reactions: Rash, itching, breathing difficulty.
Warnings and Contraindications
Pregnancy: Ambrisentan is teratogenic (causes birth defects). Mandatory negative pregnancy test before starting and monthly monitoring during treatment.
Breastfeeding: Not recommended.
Liver impairment: Use with caution; regular liver function tests required.
Fluid retention: May worsen swelling, especially in patients with left heart failure.
Do not use in: Patients with idiopathic pulmonary fibrosis (may worsen outcomes).
Drug Interactions
Cyclosporine: Increases Ambrisentan levels ā dosage adjustment needed.
Rifampin, ketoconazole, HIV protease inhibitors: May alter blood levels.
Other PAH drugs: Can be combined, but careful monitoring is necessary.
Monitoring Requirements
Patients on Ambrisentan must undergo:
Liver function tests (monthly)
Hemoglobin & hematocrit (risk of anemia)
Pregnancy test (before and during therapy for females of childbearing age)
Edema monitoring (swelling in legs/ankles)
Storage and Handling
Store at 20Ā°Cā25Ā°C (room temperature).
Protect from heat, moisture, and direct light.
Keep medication out of reach of children.
Advantages Over Other ERA Drugs
More selective for endothelin-A receptor ā fewer side effects.
Lower risk of liver damage compared to Bosentan.
Once-daily dosing makes it more convenient.
Conclusion
Ambrisentan is a highly effective and selective ERA for managing Pulmonary Arterial Hypertension (PAH). It significantly improves exercise tolerance, delays disease progression, and enhances patient quality of life. However, due to potential risks like liver damage, anemia, and teratogenic effects, strict medical supervision and regular monitoring are essential.
