Ambrisentan is a prescription oral medication, sold under the brand name Letairis, used for the treatment of pulmonary arterial hypertension. Its function is to improve a patient’s ability to exercise and to delay the clinical worsening of this specific condition. It can be prescribed by itself or in combination with other drugs, such as tadalafil, to achieve these outcomes.
How Ambrisentan Treats Pulmonary Hypertension
Pulmonary arterial hypertension, or PAH, is a form of high blood pressure that affects the arteries within the lungs and the right side of the heart. With PAH, the walls of these small lung arteries become stiff and narrow, making it harder for blood to flow through. This resistance forces the right side of the heart to work much harder to pump blood into the lungs.
Over time, this continuous strain can weaken the heart muscle, leading to symptoms such as fatigue, dizziness, and shortness of breath, particularly during physical activity. By helping to relax and widen the blood vessels in the lungs, ambrisentan reduces the workload on the heart. This action helps to slow the progression of the disease and improve a person’s capacity for exercise.
The medication is approved for patients with WHO Functional Class II or III symptoms, which categorize the severity of the condition based on how much physical activity is limited. Through its effects, ambrisentan helps manage the daily impact of PAH, allowing for better quality of life and slowing down the advancement of symptoms.
Mechanism of Action
Ambrisentan functions by targeting a substance called endothelin-1. Endothelin-1 is a naturally occurring peptide that plays a part in controlling blood vessel tone. Its primary actions include causing blood vessels to narrow, a process known as vasoconstriction, and promoting the proliferation of cells within the vessel walls.
In individuals with pulmonary arterial hypertension, the concentration of endothelin-1 in the plasma is significantly elevated. This excess contributes directly to the high blood pressure in the lung arteries that characterizes PAH. Two main receptor subtypes, endothelin type-A (ETA) and endothelin type-B (ETB), mediate the effects of endothelin-1, with the ETA receptor being mainly responsible for vasoconstriction.
Ambrisentan is classified as a selective endothelin receptor antagonist with a high affinity for the ETA receptor subtype. By binding to and blocking these ETA receptors, ambrisentan prevents endothelin-1 from exerting its constricting effect on the vascular smooth muscle. This targeted blockage allows the blood vessels in the lungs to relax and widen, lowering blood pressure in the pulmonary arteries.
Potential Side Effects and Safety Warnings
Common side effects of ambrisentan include peripheral edema, which is swelling caused by fluid retention in the hands, legs, or feet, as well as nasal congestion, sinusitis, and flushing. While most instances of edema are mild to moderate, fluid retention has been reported within weeks of starting the medication.
More serious adverse effects can also occur, including the potential for liver injury. Patients should immediately contact their doctor if they experience symptoms like nausea, vomiting, fever, dark urine, or yellowing of the skin or eyes. Regular blood tests are necessary to monitor liver function. Another potential serious side effect is anemia, a condition marked by low levels of red blood cells.
A significant safety concern associated with ambrisentan is its risk of causing embryo-fetal toxicity; it should not be taken by anyone who is pregnant. Due to this risk, ambrisentan is only available through a restricted distribution program called the Letairis REMS (Risk Evaluation and Mitigation Strategy) Program. Females who are able to become pregnant must have a negative pregnancy test before starting the drug, monthly during treatment, and one month after stopping. Effective contraception is required. The medication may also have an adverse effect on male fertility by decreasing sperm counts.
Dosage and Patient Guidelines
Ambrisentan is administered orally as a tablet, typically once daily, and can be taken with or without food. The standard dosage is either 5 mg or 10 mg, and the tablet should be swallowed whole. It is important not to stop taking ambrisentan suddenly, as this can lead to a worsening of the condition.
If a dose is missed, the patient should take it as soon as they remember. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Patients should not take two doses at the same time to make up for a missed one. The medication should be stored in its original container at room temperature, away from moisture and heat.
Certain medications can interact with ambrisentan, altering its effectiveness or increasing the risk of side effects. For instance, co-administration with cyclosporine requires that the ambrisentan dose be limited to 5 mg per day. Other drugs may also interact by affecting the enzymes that metabolize ambrisentan in the body, such as CYP3A4 and CYP2C19. Patients must inform their doctor about all medications they are taking, including prescriptions, over-the-counter drugs, and herbal supplements.