Iloprost hypertension

Alternative treatments Use of iloprost with other approved treatments for pulmonary hypertension has not been studied. If patients deteriorate while on this treatment, consider alternative treatments. 

Syncope Because of the risk of syncope, monitor vital signs while initiating iloprost. In patients with low systemic blood pressure, take care to avoid further hypotension. Do not initiate iloprost in patients with systolic blood pressure less than 85 mm Hg. Be alert to the presence of concomitant conditions or drugs that might increase the risk of syncope. Syncope can also occur in association with pulmonary arterial hypertension, particularly in association with physical exertion. 

Puimonary edema If signs of pulmonary edema occur when inhaled iloprost is administered in patients with pulmonary hypertension, stop the treatment immediately. This may be a sign of pulmonary venous hypotension. 

Speciai risk Iloprost has not been studied in patients with pulmonary hypertension, which increases mean AUC in otherwise healthy patients. 

The synthetic analogues of prostacyclin, be-raprost, treprostinil and iloprost, although also platelet aggregation inhibitors, are used to treat pulmonary arterial hypertension. 

There has been a sequential comparison of inhaled nitric oxide 40 ppm with aerosolized iloprost 14— 17 micrograms in 35 adults with primary pulmonary hypertension (125). Five of the patients had minor headache and facial flushing during inhalation of iloprost, but these symptoms were short-lived and abated a few minutes after the inhalation ended. One patient had mild jaw pain after aerosolized iloprost, but again this was shortlived. There was an unexpected increase in pulmonary artery pressure in 10 patients and vascular resistance in six patients who received nitric oxide. The authors were uncertain of the cause of this increase, as nitric oxide generally behaves as a vasodilator, but they noted that... 

Hoeper MM, Schwarze M, Ehlerding S, Adler-Schuermeyer A, Spiekerkoetter E, Niedermeyer J, Hamm M, Fabel H. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000 342(25) 1866-70. 

Schenk P, Petkov V, Madl C, Kramer L, Kneussl M, Ziesche R, Lang I. Aerosolized iloprost therapy could not replace long-term IV epoprostenol (prostacyclin) administration in severe pulmonary hypertension. Chest 2001 119(1) 296-300. 

The use of iloprost has been proposed in patients with systemic sclerosis, a disease that is often characterized by pulmonary hypertension and Raynaud s phenomenon. Three patients with systemic sclerosis who were treated with iloprost developed acute thrombotic events (3). In one case, intestinal infarction occurred 1 day after infusion of iloprost. In another patient the left kidney was not perfused 22 days after the last infusion of iloprost because of thrombosis of the left renal artery. The last patient, 9 months after the start of treatment with iloprost, and 5 days after the last infusion, had an anterolateral myocardial infarction. The authors commented that their observations did not allow them to conclude that there is a direct relation between infusion of iloprost and thrombotic events. However, they said that this possibility should be considered, and they suggested that risk factors for thromboembolism should be carefully evaluated in each patient with systemic sclerosis who is receiving iloprost. 

Inhalation of aerosolized iloprost is being tested in patients with severe primary or secondary pulmonary hypertension refractory to conventional therapy. The aim is to produce predominantly pulmonary vasodilatation without significant systemic effects. In an uncontrolled series of 19 patients, the most common adverse effects of inhaled iloprost were coughing, nausea, edema, and thoracic pain (4). In most patients, these effects were transient and rarely required a change in therapy. 

Olschewski H, Ghofrani HA, Schmehl T, Winkler J, Wilkens H, Hoper MM, Behr J, Kleber FX, Seeger W. Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group. Ann Intern Med 2000 132(6) 435 13. 

Olschewski, H., Rohde, B., Behr, J., et al. (2003), Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension, Chest, 124,1294—1304. 

VASODILATOR ANTI HYPERTENSIVES GLYCOPROTEIN llb/llla INHIBITORS t risk of bleeding when eptifibatide or tirofiban is co-administered with iloprost Uncertain at present Closely monitor the effects watch for signs of excess bleeding... 

ANTICOAGULANTS-ORAL ANTI HYPERTENSIVES AND HEART FAILURE DRUGS-VASODILATOR ANTI HYPERTENSIVES 1. Bosentan may i warfarin levels 2. Iloprost and sitaxentan may t warfarin levels 1. Uncertain postulated that bosentan induces CYP3A4 and CYP2C9 2. Uncertain Monitor INR closely... 

HEPARINS VASODILATOR ANTI HYPERTENSIVES Possible t risk of bleeding with iloprost Anticoagulant effects of heparins t by an mechanism that is uncertain at present Monitor APTT closely... 

The effects of aerosolized iloprost have been reported in three patients with severe pulmonary hypertension... 

Hoeper MM, Olschewski H, Ghofrani HA, Wilkens H, Winkler J, Borst MM, Niedermeyer J, Fabel H, Seeger W, Grimminger F, et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J Am CoU Cardiol 2000 35(l) 176-82. 

The cyclo-oxygenase metabolite prostacyclin is a potent, short-lived vasodilator and antithrombotic agent. Intravenous administration of the commercially available form of prostacyclin, epoprostenol, relieves the symptoms of primary pulmonary hypertension by dilating the pulmonary vasculature [99]. A stable prostacyclin analogue, iloprost, appears to be similarly effective when administered as an aerosol and obviates the logistical problems associated with maintained intravenous administration [100]. 

Secondary Pulmonary Hypertension. Secondary pulmonary hypertension is seen in some heart transplant candidates, and documenting the potential for reversibility when the primary defect is corrected is important in selecting appropriate heart transplant candidates and liver transplant patients as well. Aerosolized prostacyclin has been shown at least as effective as inhaled NO 40 ppm for this purpose in heart transplant candidates [170], while aerosolized epoprostenol has been shown similarly useful in liver transplant candidates. Delivery of iloprost was faster with an ultrasonic nebulizer but equally efficacious as compared to a jet nebulizer [171]. The role of aerosolized prostacyclin and related medications for pulmonary hypertension and for diagnostic evaluation of transplant candidates remains to be proven. Certainly, a successful aerosol treatment for pulmonary hypertension would be well received because of the inconvenience of the current method of constant infusion via an indwelling catheter. From an economic viewpoint, the market is small, so the chance of recovery of investment in new treatment would be limited. 

There are experiences of ambulatory treatment of patients with pulmonary hypertension, with inhaled nitric oxide and with prostaglandins, in both cases using an ambulatory delivery system. In our center we have an outpatient treatment program of pulmonary hypertension with inhaled iloprost leading in some patients to significant improvement in pulmonary hypertension and in the quality of life with no adverse effects. 

Iloprost (prostaglandin PG12) For pulmonary arterial hypertension... 

Finally, a comprehensive hemodynamic evaluation in IPAH patients should include assessment of pulmonary vasoreactivity with inhaled nitric oxide (10-40 ppm), inhaled iloprost, IV epoprostenol, or adenosine in patients with precapillary hypertension. If with these treatments mPAP decreases by 10 mm Hg to levels <40 mm Hg, IPAH patients are considered responders. This denotes a small but very important population (<15% of IPAH patients) with significantly improved outcomes when treated with high doses of calcium channel blockers (29,30). For the select patients who are deemed responders and are subsequently treated with calcium antagonists, close follow-up to confirm a sustained hemodynamic improvement is essential. 

McLaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med 2006 174 1257-63. 

Currently, prostanoids are administered for various therapeutic interventions e.g., 1) treprostinil, beraprost, and iloprost (Fig. 3) are analogs of PGI2 (prostacychn) which are used to treat pulmonary arterial hypertension (PAH) to overcome the drawback of short circulation... 

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