FDA-approved Treatments for Pulmonary Hypertension
Vasodilator & Anti-Proliferative Agents
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.
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 medications. As of April 2005, Ventavis is approved for use in patients in World Health Organization 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 and Remodulin, Ventavis is an inhaled medication, administered via a nebulizer, that is recommended for use between 6-9 times daily. Side effect profile of Ventavis is similar to Flolan 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.
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 PPH 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.
Sildenafil (Revatio)
As a result of small but favorable studies, sildenafil was tested and found useful in recent trials in 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.
Calcium Channel Blockers and Other Therapies
Currently, several medications continue to be under active investigation and/or pending FDA approval for use in PAH:
- Inhaled Treprostinil– may allow for less frequent dosing
- Sitaxsentan – a selective endothelin antagonist expected to have FDA approval in 2006
- Ambrisentan – also a selective endothelin antagonist
- Cialis – long acting phosphodiesterase inhibitor which may allow less frequent dosing than sildenafil
Calcium Channel Blockers
Diltiazem and Nifedipine (and more recently amlodipine) are used in some patients with pulmonary hypertension. Enthusiasm for this class of medications has decreased over the past few years. Approximately 10% of patients may benefit in the short term, and even fewer over the long term. Patients with Raynaud’s (painful color change of the fingers on exposure to cold) often find their symptoms improved while on calcium channel blockers.
Blood Thinners
Warfarin, (Coumadin) is prescribed for most patients with pulmonary hypertension. There is some data from research studies that this medication may improve survival. It requires monitoring to adjust the dose. There are many medications and foods that interact with warfarin. In general, patients on Warfarin should avoid aspirin containing products.
Diuretics
Most if not all patients with pulmonary hypertension will require a diuretic to prevent retention of salt and water. Commonly prescribed agents include furosemide (Lasix), bumetinide (Bumex), and spironolactone (Aldactone). These medications are prescribed once daily initially, but in patients with more advanced disease, escalated dosing and combination is often required. Patients must pay close attention to their diets and avoid high salt foods and limit their intake of liquids. Periodic monitoring of blood chemistries is required, and many patients require supplemental potassium.
Digoxin (Lanoxin)
This very old medication is used in certain patients with pulmonary hypertension, particularly patients with advanced disease. It may help the heart pump more effectively. Patients with kidney failure may need to have Digoxin levels monitored very carefully.
Oxygen
Patients with low oxygen levels benefit from oxygen therapy. Low oxygen levels in the lungs causes the pulmonary arteries to constrict, thereby worsening pulmonary hypertension. Some patients may require supplemental oxygen only with exertion or sleep; others will need continuous therapy.
