Getting The Most From Your PAH Therapy

We would like to introduce a new series on PulmonaryHypertensionRN.com.  This series will include periodic articles focusing on a specific therapy and how to benefit maximally and minimize side effects.

PAH medicationsLetairis (Ambrisentan) Efficacy in Pulmonary Hypertension

This medicine was first approved in 2007 based on 2 studies that both showed improvement in exercise capacity and reduction in the rate of clinical worsening over 12 weeks.  Subsequent studies have amplified on the efficacy of this medicine.  The recently reported AMBITION study powerfully showed 50% reductions in the rates of clinical decline over a several year period.  The benefits were maximal when combined with Adcirca (Tadalafil).  The combination of Letairis and Adcirca together was much more effective than either medicine alone.

Maximizing the Efficacy of Letairis

Is 10mg better than 5mg?  This is a difficult question to answer definitively.  In the 12 week study there was not a clear difference in improvement in exercise capacity.  There was a strong suggestion that the higher dose lowered pulmonary artery pressures a bit more.  In the AMBITION study, most patients were titrated to the 10mg dose over a period of a few weeks.  So our best data regarding long-term benefit is with the 10mg dose.  My practice is to start with 5mg once daily for a one to three months and reassess.  For patients that are not troubled by any side effects, then I generally move the dose to the 10mg once daily.   If patients are struggling with side effects, then I leave the dose at 5mg once daily for six months and reassess.

I generally encourage patients to take the medication with food although it may be taken on an empty stomach.  Most patients take the medication in the morning but this is not a necessity.

We have compelling data that Letairis is effective as monotherapy.  However, with the addition of the AMBITION clinical trial results, we can say with confidence that the combination of Letairis with Adcirca is even more effective.  We don’t know if Letairis combined with Revatio (Sildenafil) is as effective as Letairis combined with Adcirca.

Side Effects of Letairis

Common side effects with Letairis and strategies to deal with them are listed below.

1.     Nasal congestion.

This is the most common side effect in my experience and  is dose related (10mg results in more nasal congestion than 5mg).  For most patients it is mild in severity and requires no specific action.  For some patients it can be very frustrating (especially patients that use supplemental oxygen).  I have a series of treatments to help with nasal congestion.  First, I make sure that the nasal congestion is due to the Letairis and not seasonal allergies.  A careful history can usually tease this apart.

Once I am convinced that the nasal congestion is due to Letairis, my first line treatment is nasal saline spray.  This can be used very frequently throughout the day.  Nasal saline does not require a prescription and it is relatively inexpensive.  There are no risks to using nasal saline spray.  If this proves inadequate, then my next strategy is to try Nasal Atrovent (Ipratropium bromide spray).  Nasal Atrovent is a drying agent that may help with congestion.  This spray may be used twice daily.  Next I try Astelin (Azelastine), a nasal antihistamine.  It may be used twice daily.  If this does not help then I try a nasal steroid spray such as Flonase (Fluticasone Nasal Spray).  Flonase may be used once or twice daily.

In rare cases where the nasal congestion is very severe and not responding to treatment with the aforementioned medications, I will reduce the dose if the patient is taking 10mg.  If the patient is already taking 5mg then I will consider switching from Letairis to Opsumit (Macitentan).

2.     Flushing.

This side effect is usually mild.  Patients notice a feeling of warmth.  This may occur periodically during the day.  Some patients notice that they appear mildly red in the face during episodes.  Most importantly, the flushing sensation does not mean that anything bad is about to happen.  The first few times patients experience the sensation it can be quite surprising.  After a few episodes patients become more at ease and most do not find this a major problem.

Letairis is absolutely forbidden in women who are or may become pregnant. All women of child bearing potential must be enrolled in a monitoring program that requires a pregnancy test prior to starting therapy and each month. Effective birth control must be used.

Always consult your treating physician before making any medication decisions.