- Aust Prescr 2004;27:76-9
- 1 June 2004
- DOI: 10.18773/austprescr.2004.063
Ampoules containing 20 microgram (10 microgram/mL) nebuliser solution
Approved indication: pulmonary hypertension
Australian Medicines Handbook section 6.7.3
Increased pressure in the pulmonary artery may have no obvious cause or it may be secondary to conditions such as thromboembolism and connective tissue diseases.1 It leads to signs of right-sided heart failure, such as peripheral oedema and liver enlargement.
Some secondary causes can be treated. For example, pulmonary artery hypertension due to chronic thromboembolism may respond to pulmonary thromboendarterectomy. Some patients with advanced disease may live long enough to receive a heart-lung transplant.
Patients with pulmonary hypertension may have an imbalance of prostacyclin and thromboxane A2. Giving an analogue of prostacyclin may therefore induce vasodilatation and reduce pressure in the pulmonary artery. Epoprostenol was approved for use in primary pulmonary hypertension in 2002, but it has to be given by continuous intravenous infusion. Treprostinil was approved in 2003, but requires continuous subcutaneous infusion. Iloprost is also an analogue of prostacyclin, but it can be given by inhalation.
Patients inhale a nebulised solution over 5-10 minutes. The serum concentration of iloprost peaks at the end of the inhalation but declines rapidly. Iloprost is extensively metabolised and none can be detected an hour after the inhalation. Some patients will need to take a dose nine times a day. Most of the metabolites are excreted in the urine, so clearance can be reduced by renal and hepatic dysfunction.
A randomised-controlled trial compared iloprost with an inhaled placebo in 203 patients with primary or secondary pulmonary hypertension. After 12 weeks, function had improved in 16.8% of the patients given iloprost, but only in 4.9% of those given a placebo.2
Another study enrolled 31 patients with primary pulmonary hypertension and followed them for a year. The mean pulmonary artery pressure was reduced in the 24 people who completed the study. This was associated with an increased exercise capacity.3
While dyspnoea improves with iloprost, coughing is common in the first weeks of treatment. Patients may also complain of flushing and pain in the jaw. Other common adverse effects are hypotension, syncope, trismus and headache.
Although iloprost is significantly better than placebo the absolute benefits are limited. In the placebo-controlled study patients given iloprost for 12 weeks were able to walk an extra 36.4 metres in six minutes.2 Few of the patients with secondary pulmonary hypertension gained much benefit. Iloprost has been approved for secondary pulmonary hypertension for a strictly limited range of conditions.
Inhaled iloprost is likely to be cheaper than intravenous epoprostenol, but epoprostenol is proven to increase survival in patients with primary pulmonary hypertension. In contrast to the other prostacyclin analogues, iloprost is given intermittently. It is uncertain whether there could be a rebound in the pulmonary artery pressure between inhalations.
In addition to the prostacyclin analogues bosentan, an oral endothelin receptor antagonist, is also available to treat primary pulmonary hypertension. Comparative studies are therefore needed to determine the best medical therapy.