Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Flolan (GlaxoSmithKline)
vials containing 500 microgram as freeze-dried powder
Approved indication: primary pulmonary hypertension
Australian Medicines Handbook section: 7.1
Primary pulmonary hypertension is a serious, but rare, condition. A rise in pulmonary artery pressure leads to right ventricular failure and death. The median survival time is less than three years, so patients may die while waiting for a transplant.
Treatment regimens include anticoagulants and the use of vasodilators to reduce pulmonary vascular resistance. Epoprostenol (formerly known as prostacyclin or prostaglandin I2) is a vasodilator which also inhibits platelet aggregation.
In an eight-week randomised trial, 11 patients with primary pulmonary hypertension were given a continuous infusion of epoprostenol. Compared with 12 patients who received conventional therapy, the infusion group had reductions in pulmonary artery pressure and total pulmonary resistance. Both groups were able to walk further after treatment.1
All the patients who completed the study were able to continue treatment with epoprostenol in an uncontrolled trial. This found that the survival of patients with severe symptoms (New York Heart Association class III or IV) increased. Their three-year survival rate was 63% compared with 41% in a group of historical controls.2
Improved survival was also seen in a prospective study of 81 patients with class III or IV heart failure. All 41 of the patients given epoprostenol survived, but eight of the 40 people in the control group died during the 12-week study.3
Epoprostenol is too unstable to be given orally. Its intravenous half-life is less than six minutes so it has to be given by continuous infusion. In the clinical trials each patient used a portable infusion pump connected to a central venous catheter. The infusion should not be stopped suddenly as the patient can deteriorate within minutes. Adjustments to the infusion rate must be done under observation so that heart rate and blood pressure can be monitored for several hours.
As epoprostenol is a vasodilator its acute adverse effects include hypotension, flushing and headache. Other common adverse effects reported in the clinical trials include tachycardia, jaw pain, myalgia, nausea and diarrhoea.
The indwelling catheter is a risk for infection and more than 20% of patients may develop local infections. In the long-term trial the drug delivery system was implicated in half the deaths.2 Patients must therefore be taught how to prepare the drug and how to care for their catheter to minimise the risk of sepsis.
Epoprostenol may have an effect on coagulation but as the patients are also usually taking anticoagulants they should already be being routinely monitored for signs of bleeding. The clearance of digoxin is temporarily reduced by epoprostenol.
Although treatment with epoprostenol has risks, it appears to improve survival and quality of life.3 Its haemodynamic effects may delay the need for transplant surgery and improve the outcomes for people who need to have surgery. Epoprostenol is also being studied in patients with other causes of pulmonary hypertension, such as scleroderma.
