Combination of Ambrisentan and Tadalafil
Pharmacological agents with different mechanisms of action are often used in combination for the treatment of many health conditions. There is the proposition in medicine that combining pharmacological agents with different mechanisms generally provides superior results than increasing the dosage of a single agent. When we increase the dosage of a medication, every increment of efficacy is coupled with an increase in the risk for adverse effects. Combining agents with different mechanisms of actions can often produce the same desired therapeutic effect at lower doses of each agent. In the treatment of pulmonary hypertension, the combination associated with the best efficacy that we know today, is the combination of tadalafil and ambrisentan for patients with WHO functional class II or III pulmonary arterial hypertension (PAH).
Tadalafil is a phosphodiesterase-5 inhibitor, while ambrisentan is an endothelin receptor antagonist. One major randomized trial of 500 newly diagnosed patients with PAH who had WHO class II or III symptoms compared the effect of the oral combination regimen of tadalafil 40mg plus ambrisentan 10mg versus taking either agent alone. The study was titled “Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension”, also known as the AMBITION study, and published in the New England Journal of Medicine in 2015. The study successfully demonstrated the combined regimen of ambrisentan and tadalafil resulted in a 50% reduction in the rate of clinical failure (18% versus 31%) and significantly improvement in exercise capacity (49 metres versus 24 metres).
Currently, the AMBITION trial results provides the main basis in support of the recommendation of the combination of ambrisentan plus tadalafil for PAH patients. Studies of combinations of other agents from the same drug families, namely sildenafil (phosphodiesterase-5 inhibitor) plus bosentan (endothelin receptor antagonist), however, have produced mixed results. It is possible that the less favorable results with the combination of bosentan plus sildenafil may be due to the drug-drug interaction between the two agents. When taken together, bosentan can increase the metabolism of sildenafil resulting in a reduction in the blood concentration of sildenafil. On the other hand, tadalafil and ambrisentan do not have any significant drug-drug interactions.
You can visit our website or consult our pharmacist toll-free by phone to learn how we can help PAH patients with affordable access to medications including ambrisentan (Letairis/Volibris), tadalafil (Cialis/Adcirca), bosentan, sildenafil, and many others.