FDA-approved Treatments
for Pulmonary Hypertension
VASODILATOR & ANTI-PROLIFERATIVE AGENTS
This is the first drug specifically approved for the treatment of pulmonary hypertension. Flolan is the most effective drug for the treatment of advanced disease. Studies have shown the drug to be effective in pulmonary arterial hypertension (PAH), as well as pulmonary hypertension related to scleroderma, lupus, congenital heart disease, diet-pill associated and stimulant associated pulmonary hypertension (PH). Flolan requires a substantial commitment from the patient. This medication is delivered by a continuous infusion via a special intravenous catheter. The medication must be mixed on a daily basis and kept refrigerated. Meticulous attention must be paid to catheter care to prevent serious infections. Common side effects include headache, jaw discomfort, flushing, rashes, and stomach upset. In patients with advanced disease, this medication improves exercise capacity and survival. Periodic monitoring of blood counts is required.
Epoprostenol (Flolan)
This is the first drug specifically approved for the treatment of pulmonary hypertension. Flolan is the most effective drug for the treatment of advanced disease. Studies have shown the drug to be effective in pulmonary arterial hypertension (PAH), as well as pulmonary hypertension related to scleroderma, lupus, congenital heart disease, diet-pill associated and stimulant associated pulmonary hypertension (PH). Flolan requires a substantial commitment from the patient. This medication is delivered by a continuous infusion via a special intravenous catheter. The medication must be mixed on a daily basis and kept refrigerated. Meticulous attention must be paid to catheter care to prevent serious infections. Common side effects include headache, jaw discomfort, flushing, rashes, and stomach upset. In patients with advanced disease, this medication improves exercise capacity and survival. Periodic monitoring of blood counts is required.
Epoprostenol (Veletri)
Veletri is a new formulation of Epoprostenol approved by the FDA in 2010 for the treatment of PAH, as well as pulmonary hypertension related to scleroderma, lupus, congenital heart disease, diet-pill associated and stimulat associate PH. It is for patient with severe disease that have not responded to conventional therapy. Substantial commitment is required from the patient in order to use this medication as it is a continuous infusion via an intravenous catheter via an ambulatory infusion pump. Different to Flolan, Veletri requires less frequent mixing and does not have to be continuously refrigerated. The side effects are the same as with Flolan and again meticulous attention must be paid to catheter care to prevent serious infections.
Treprostinil (Remodulin)
This medication is structurally related to epoprostenol (Flolan). It is approved for the treatment of PAH, and pulmonary hypertension due to connective tissue disease. There is also experience with this drug in congenital heart disease. Studies have shown that Remodulin increases exercise tolerance and decreases pulmonary artery pressure. The drug is delivered by a continuous infusion either intravenous or subcutaneous. If indicated, the subcutaneous formulation is infused underneath the skin in the abdomen via a very small plastic catheter. Side effects are similar to Flolan. Although the delivery system is complex, it is somewhat less so than Flolan. Remodulin does not need to be mixed or refrigerated. Infusion site pain for the subcutaneous formulation remains a significant problem with this medication for many patients. Periodic monitoring of blood counts is required.
Iloprost (Ventavis)
Like Flolan and Remodulin, Ventavis is also a prostanoid medication. As of April 2005, Ventavis was approved for use in patients in World Health Organization (WHO) group I which includes patients with idiopathic PAH, familial PAH, associated PAH (collagen vascular disease, congenital heart disease, stimulant associated, portal hypertension, etc), PAH associated with venous or capillary disease, and persistent PH of the newborn. Unlike Flolan, Veletri and Remodulin, Ventavis is an inhaled medication, administered via a nebulizer. It is recommended for use between 6-9 times daily. Side effect profile of Ventavis is similar to Flolan, Veletri and Remodulin. However, patients report less flushing & diarrhea. Patients with a history of asthma or emphysema may need to be cautious at the time of initiation since worsening cough and breathing may result.
Treprostinil (Tyvaso)
Tyvaso, like Ventavis, is also an inhaled prostanoid medication. It was approved in July 2009 for use in patients with WHO group I PAH that are suffering from moderate to severe symptoms in order to increase walk distance. The dosing regimen is not as frequent as Ventavis, only requiring use 4 time per day with increasing number of breaths per dose as the patient is optimized on therapy. The medication is delivered via a specialized and individualized nebulizer device. The side effect profile is once again similar to that of the previously discussed medication but again tends to have less flushing and diarrhea. Tyvaso does tend to cause increased sore throat and cough with initial use.
Bosentan (Tracleer)
This is the first oral medication specifically approved for the treatment of pulmonary hypertension. It is approved for patients with advanced disease due to PAH or connective tissue disease associated pulmonary hypertension. In research studies, the medication was shown to increase exercise tolerance and decrease clinical worsening compared to placebo. Approximately 10% of patients taking this drug will develop elevated liver function tests. As a result, monthly monitoring is required. A smaller percentage of patients may also experience a decrease in hemoglobin. Periodic monitoring of blood counts and liver function test is required. This drug is absolutely contraindicated in women who are or could become pregnant. For sexually active women, two methods of birth control are recommended and monthly pregnancy tests are also mandatory.
Ambrisentan (Letairis)
Letairis is in the same class of medication as Tracleer. It gained its initial FDA approval in May 2009 for treatment of PAH WHO group I to improve exercise ability and delay clinical worsening. The studies that established effectiveness predominantly included patients with moderate to severe disease with idiopathic, heritable or PAH associated with connective tissue diseases. Letairis is a once a day medications (Tracleer needs to be taken twice a day). Unlike Tracleer, it has not been shown to have the predilection to increase liver enzymes and was approved by the FDA in early 2011 to not require routine blood tests to evaluate the liver. Treatment with Letairis does require all women of childbearing potential to use two acceptable methods of contraception and have monthly pregnancy tests.
Sildenafil (Revatio)
As a result of small but favorable studies, sildenafil was tested and found useful in trials for patients with New York Heart Association (NYHA) Class II-IV pulmonary arterial hypertension. Sildenafil is an active vasodilator and allows for improved pulmonary blood flow. Sildenafil is currently approved for patient with PAH in the formulation of Revatio. The usual dose of 20 mg three times daily is the current recommendation by the FDA. However, patients with severe PAH may often require higher, and more frequent, dosing. Although used for erectile dysfunction in men, sildenafil has not been shown to affect sexual desire in men, nor does it have any effect in women. Side effects of sildenafil include headache, back pain, and flushing. The use of sildenafil is contraindicated in patients using nitrate containing medications such as isordil or sub-lingual nitroglycerin. Other drug interactions include alpha-blockers (such as Doxazosin), certain antibiotics, and verapamil (which may increase sildenafil serum concentration). Bosentan and sildenafil, when taken together, co-interact and result in elevated bosentan and decreased sildenafil levels. Patients with coronary artery disease need to notify their physician before using sildenafil.
Tadalafil (Adcirca)
Adcirca is an oral medication with similar affects as Revatio but is formulated for 1 time a day dosing. It has been approved for the treatment of PAH WHO group I with moderate to severe disease to improve exercise tolerance shown by increased 6-minute walk test and increases time to clinical worsening. It has been shown to improve patient compliance due to the once a day dosing. It is not to be used with concurrent use of organic nitrates in any form. Patient are often monitored directly by a physician during their first dosing as it can cause low blood pressure.