Iloprost is metabolized principally via β-oxidation of the carboxyl side chain. The main metabolite is tetranor-iloprost, which is found in the urine in free and conjugated form. In animal experiments, tetranor-iloprost was pharmacologically inactive.
Iloprost, an inhalation solution, is sold under the name Ventavis® and is used to treat pulmonary arterial hypertension (PAH). It was developed by the pharmaceutical company Schering AG and is marketed by Schering AG in Europe and Actelion Pharmaceuticals in the USA.
Iloprost is a synthetic analogue of prostacyclin PGI2. Iloprost dilates systemic and pulmonary arterial vascular beds. It also affects platelet aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer.
Dosage and administration
In the U.S., iloprost is intended to be inhaled specifically using the I-Neb® AAD® or Prodose® AAD® delivery systems. Iloprost has not been approved for use with other brands of nebulizers.
The approved dosing regimen for iloprost is 6 to 9 times daily (no more than every 2 hours) during waking hours, according to individual need and tolerability. The significant clinical effects observed in the pivotal study of patients with PAH were achieved with a median dose of 30 mcg per day (range: 12.5 to 45 mcg delivered at the mouthpiece), corresponding to 6 daily inhalations of 5 mcg. The majority of patients (> 80%) in the pivotal study used this median dose or a higher dose with an excellent treatment compliance after 12 weeks.
The first inhaled dose of iloprost should be 2.5 mcg (as delivered at the mouthpiece). If this dose is well tolerated, dosing should be increased to 5 mcg and maintained at that dose. Any patient who cannot tolerate the 5 mcg dose should be maintained at 2.5 mcg.
Each inhalation treatment requires one entire single-use ampule. Each single-use ampule delivers a concentration of 10 mcg/mL to the medication chamber of either the I-Neb® AAD® or Prodose® AAD® System, and delivers a nominal dose of either 2.5 mcg or 5.0 mcg to the mouthpiece. After each inhalation session, any solution remaining in the medication chamber should be discarded. Use of the remaining solution, even if the reservoir is “topped off” with fresh medication, will result in unpredictable dosing. Patients should follow the manufacturer’s instructions for cleaning the I-Neb® AAD® or Prodose® AAD® System components after each dose administration.
Complete information regarding use of iloprost in specific populations (e.g. nursing mothers, pediatrics, patients with hepatic or renal impairment), drug interactions, and overdosage can be found in full prescribing information.
Iloprost as Ventavis is intended for inhalation administration only via the I-Neb® AAD® or Prodose® AAD® Systems, pulmonary drug delivery devices. It has not been studied with any other nebulizers.
Vital signs should be monitored while initiating inhaled iloprost therapy. Dose adjustments or a change in therapy should be considered if exertional syncope occurs. Inhaled Iloprost should not be initiated in patients with systolic blood pressure lower than 85 mm Hg. Iloprost should be stopped immediately if signs of pulmonary edema occur. This may be a sign of pulmonary venous hypertension. Iloprost has not been evaluated in patients with chronic obstructive pulmonary disease (COPD), severe asthma, or with acute pulmonary infections.
Should signs of pulmonary edema occur when inhaled iloprost is administered in patients with pulmonary hypertension, the treatment should be stopped immediately. This may be a sign of pulmonary venous hypertension.