Ambrisentan is an oral medication classified as a selective Endothelin Receptor Antagonist (ERA). It is primarily used to treat Pulmonary Arterial Hypertension (PAH), a serious, progressive disease characterised by high blood pressure in the arteries of the lungs. By relaxing the blood vessels in the lungs, Ambrisentan helps to reduce the workload on the heart, improve exercise capacity, and slow the progression of the disease. The standard starting dose is 5mg, taken once daily.

Ambrisentan is a medicine used to treat pulmonary arterial hypertension (PAH), a condition in which the blood vessels in the lungs become narrowed and stiff. This increases pressure in the lungs and makes it harder for the heart to pump blood, leading to symptoms such as shortness of breath, tiredness, and reduced ability to exercise.

In PAH, the body produces too much endothelin-1, a naturally occurring substance that causes blood vessels to tighten and promotes thickening of the vessel walls. Ambrisentan works by selectively blocking the endothelin type A (ETA) receptor, which is responsible for most of these harmful effects.

By blocking the ETA receptor, Ambrisentan helps relax the blood vessels in the lungs and reduces abnormal cell growth in the vessel walls. This leads to wider pulmonary arteries, lower resistance to blood flow, and improved blood circulation through the lungs. As a result, patients may experience improved breathing, reduced fatigue, and better exercise tolerance, such as an increased distance walked during a 6-minute walk test.

Ambrisentan is more selective for the ETA receptor than for the endothelin type B (ETB) receptor. Preserving ETB receptor activity is important because it helps clear endothelin-1 from the bloodstream and supports the release of natural vessel-relaxing substances.

Because PAH is a serious and complex condition, treatment with Ambrisentan is usually started and closely monitored by a healthcare professional who specialises in pulmonary hypertension.

Ambrisentan is indicated for:

Treatment of Pulmonary Arterial Hypertension (PAH):

Specifically, WHO Functional Class II and III to improve exercise ability and decrease the rate of clinical worsening.

Combination Therapy:

Used alone or in combination with other agents (e.g., PDE-5 inhibitors like Tadalafil) to manage PAH.

Improved Hemodynamics:

Reduces pulmonary vascular resistance and pulmonary artery pressure.

Enhanced Exercise Capacity:

Improves patient functional status, often measured by increased 6-minute walk distance.

Slower Disease Progression:

Helps delay the time to clinical worsening in PAH patients.

Once-Daily Dosing:

Provides convenience and promotes better patient adherence to therapy.

Ambrisentan can be associated with various side effects, some of which require immediate medical attention or regular monitoring.

Common Side Effects (Usually Mild):

• Peripheral oedema (swelling of ankles and legs)
• Headache
• Anaemia (decrease in haemoglobin and hematocrit)
• Nasal congestion (stuffy nose)
• Flushing

Serious Side Effects (Stop taking the medicine and seek urgent medical attention if you experience):

• Severe Liver Problems (Hepatotoxicity): Symptoms include severe nausea, vomiting, yellowing of the skin or eyes (jaundice), dark urine, or unexplained fatigue.
• Fluid Retention/Heart Failure: Sudden, significant weight gain or swelling, or difficulty breathing, which may indicate heart failure or worsening PAH.
• Angioedema: Swelling of the face, lips, tongue, or throat, which can impair breathing.
• Hypotension: Severe dizziness or fainting due to dangerously low blood pressure.

• Dosage: The typical starting dose is 5mg once daily. If tolerated, the dose may be increased to 10mg once daily as determined by the prescribing specialist.
• Administration: Take the tablet orally, once daily, with or without food. Swallow the tablet whole. Do not cut, crush, or chew the tablet.
• Consistency: Take Ambrisentan at the same time each day to maintain stable blood levels. Never discontinue this medication abruptly without consulting your physician.

Ambrisentan functions as a highly selective Endothelin Receptor Antagonist (ERA), primarily targeting the Endothelin Type A (ET_A) receptor.

1. Endothelin-1 Blockade: In PAH, high levels of the peptide Endothelin-1 (ET-1) cause excessive vasoconstriction and cell proliferation in the pulmonary arteries.
2. Receptor Selectivity: Ambrisentan binds competitively to the ET_A receptor on vascular smooth muscle cells, preventing the powerful ET-1 from binding.
3. Vasodilation: By blocking the ET_A receptor, the potent vasoconstrictive signals are inhibited, leading to the relaxation and widening of the pulmonary blood vessels (pulmonary vasodilation).
4. Reduced Resistance: This vasodilation results in a decrease in Pulmonary Vascular Resistance (PVR), lowering the pressure in the pulmonary arteries and easing the burden on the right side of the heart.

• Do not stop suddenly: Stopping Ambrisentan without medical advice can make pulmonary arterial hypertension (PAH) worse. Always talk to your specialist before stopping or changing the dose.
• Attend regular monitoring: Keep all scheduled appointments for required blood tests, including monthly liver function tests and, if needed, monthly pregnancy tests. These tests help make sure the medicine is safe for you.
• Watch for swelling: Swelling of the ankles, feet, or legs can occur. Contact your healthcare team if swelling becomes severe, happens quickly, or is accompanied by sudden weight gain or worsening shortness of breath.
• Use reliable contraception: This medicine can harm an unborn baby. Women who could become pregnant must use two reliable methods of birth control during treatment and for the advised time after stopping.
• Report new or unusual symptoms: Tell your doctor or nurse if you feel unusually tired, dizzy, faint, have chest discomfort, or notice symptoms such as nausea, dark urine, or yellowing of the skin or eyes.

• Store at room temperature, ideally between 20°C and 25°C (68°F and 77°F).
• Keep the tablets in their original packaging, protected from light and moisture.
• Keep out of reach and sight of children.

• Grapefruit Products: No specific warnings exist, but it is generally wise to avoid excessive intake of grapefruit and its juice, as it can affect the metabolism of many oral medications.
• General: Ambrisentan can be taken independently of meals.

• Cyclosporine A: Using Ambrisentan with cyclosporine can greatly increase the amount of Ambrisentan in your blood. This combination is usually avoided, or the dose must be reduced with close medical monitoring.
• Rifampin: Rifampin can lower the level of Ambrisentan in the body, which may make it less effective. Your doctor may avoid this combination or monitor your response closely.
• Strong enzyme inhibitors (such as ritonavir or ketoconazole): These medicines may slightly increase Ambrisentan levels. Careful monitoring for side effects is recommended.
• PDE-5 inhibitors (such as sildenafil or tadalafil): These are commonly used together with Ambrisentan to treat PAH. Blood pressure should be monitored, as using them together may increase the risk of low blood pressure. Always tell your healthcare provider about all medicines, supplements, or herbal products you are taking before starting or changing Ambrisentan.

• Severe Hepatic Impairment (Liver Disease): CONTRAINDICATED. The drug is primarily metabolised by the liver, and severe impairment increases the risk of toxicity.
• Anaemia: Use with caution, as the drug can cause a dose-dependent decrease in haemoglobin levels, which may necessitate blood transfusions or discontinuation of therapy.
• Left-Sided Heart Disease: Should not be used in PAH patients who also have significant left-sided heart disease, as it could worsen pulmonary congestion.

The typical starting daily dose is 5mg taken once daily. The dose may be increased to a maximum of 10mg once daily based on patient tolerability and therapeutic response, under the guidance of a specialist.

If you miss a dose, take it as soon as you remember that same day. If the next day has already arrived, skip the missed dose and return to your regular once-daily schedule. Do not take two doses at the same time.