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.
Remodulin (Orphan)
20 mL vials containing 1 mg/mL, 2.5 mg/mL, 5 mg/mL and 10 mg/mL
Approved indication: pulmonary arterial hypertension
Australian Medicines Handbook section 6. 7. 3
Pulmonary arterial hypertension is a rare condition and there has been criticism that Australian patients have not had access to effective therapy.1 The approval of treprostinil will increase the options for patients with severe pulmonary arterial hypertension (bosentan and epoprostenol are already available), but hospitals will have to grapple with its cost.
Treprostinil is an analogue of prostacyclin, the natural substance which causes vasodilatation and inhibits platelet aggregation. The haemodynamic effects of treprostinil include reduced pulmonary and systemic vascular resistance.
The drug is given by continuous subcutaneous infusion. Infusion rates are adjusted over several weeks to achieve a balance between improved symptoms and adverse effects. Most of the dose is metabolised in the liver and then excreted in the urine. The half-life is 2-4 hours.
A double-blind trial compared treprostinil to placebo in 470 patients with pulmonary artery hypertension (New York Heart Association (NYHA) functional class II-IV). After 12 weeks there were haemodynamic improvements and a dose-related increase in exercise capacity in the treprostinil group.2
Approximately 8% of the participants discontinued treprostinil because of pain at the infusion site. This problem affected 85% of the patients.2 In addition to problems related to the infusion system, common adverse events include diarrhoea, pain in the jaw, flushing and oedema. As treprostinil inhibits platelets, bleeding, such as gastrointestinal haemorrhage2, can occur.
Although dyspnoea improved during treatment with treprostinil, the increase in exercise capacity was small. At the start of the study the patients could walk 326 metres in six minutes. The median increase after treatment was 10 metres. Sicker patients tend to improve the most so treprostinil is only approved for patients in the NYHA III-IV functional class.
While it is unknown if treprostinil will have a similar effect on survival as epoprostenol, it has the advantage of not requiring intravenous infusion. It is possible to change patients from epoprostenol to treprostinil, but this has only been reported in patients with life-threatening complications of intravenous treatment.3 Treprostinil has not been compared with bosentan, an oral endothelin receptor antagonist, which is considerably cheaper.
