A single dose of inhaled iloprost 5mcg was administered via 3 different pulmonary drug delivery devices in a Phase I, single-dose, crossover pharmacokinetic and pharmacodynamic trial to 13 patients with various forms of PAH.1,23
Increased serum concentrations of iloprost appeared within 10 to 20 minutes of beginning inhalation with all 3 devices, and peak concentrations were achieved at the end of the inhalation (ie, 9 to 12 minutes) or within 5 minutes after inhalation.1,23
This same trial provided information about the hemodynamic effects of inhaled iloprost. Immediately after inhalation, iloprost reduced mean PVR by approximately 35.5 - 38.0, with PVR returning to baseline within 60 to 120 minutes. Inhaled iloprost also decreased mean PAP and slightly increased mean cardiac output over pre-inhalation values. Systemic heart rate and blood pressure remained unchanged. Plasma concentrations were undetectable 30 minutes after inhalation.23
In studies in normal volunteers there was no pharmacodynamic interaction between intravenous iloprost and either nifedipine, diltiazem, or captopril.1 However, iloprost has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents. Since iloprost inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants.1
In vitro studies reveal that cyctochrome P450-dependent pathways play only a minor role in the metabolism of iloprost.1
The AIR trial compared the effect of 3 months of inhaled iloprost versus placebo and evaluated changes in walk distance at peak and trough levels. When walk distance was measured immediately prior to inhalation, the improvement compared to placebo was approximately 60% of the effect seen at 30 minutes after inhalation. To assess "long-term" effects, hemodynamics before inhalation (expected trough condition) and at the end of inhalation (expected peak condition) at week 12 were compared with the pre-inhalation values obtained at baseline. A significant improvement was observed for mPAP, PVR, and SvO2 at the peak measurement in the iloprost group (p < 0.05). At 12 weeks, patients were stable compared with baseline for trough values.4
In clinical studies, common adverse reactions due to Ventavis included: vasodilation (flushing, 27%), cough (39%), headache (30%), flu syndrome (14%), nausea (13%), trismus (12%), hypotension (11%), insomnia (8%), and syncope (8%). Other pre-marketing serious adverse events reported with the use of Ventavis included congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.1
Vital signs should be monitored while initiating Ventavis. In patients with low systemic blood pressure, care should be taken to avoid further hypotension. Ventavis should not be initiated in patients with systolic blood pressure less than 85 mm Hg. Physicians should be aware of 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. The occurrence of exertional syncope may reflect a therapeutic gap or insufficient efficacy, and the need to adjust dose or change therapy should be considered.1
Ventavis should be taken 6 to 9 times per day during waking hours, according to individual need and tolerability (but not more than once every 2 hours). In the randomized, placebo-controlled, Phase 3 clinical trial, the mean number of inhalations per day was 7.3 and 90% of patients in the iloprost group never inhaled study medication during sleeping hours.1
The I-neb AAD System uses Adaptive Aerosol Delivery (AAD) technology to precisely and reproducibly deliver Ventavis to every patient, at either dose (2.5 mcg or 5.0 mcg), using a single ampule of medication.
The I-neb AAD System monitors a patient's unique breathing pattern and continually adapts to breathing changes during treatment to deliver a precise dose. The I-neb AAD System delivers aerosolized Ventavis during the first 80% of inhalation, ensuring no medication is wasted in the deadspace on inhalation or lost to the environment on exhalation.2 With the I-neb AAD System, a medication chamber controls the dose and a control disc operates the I-neb AAD System. Once a patient receives a complete dose, the I-neb AAD System stops delivering aerosol and signals the user with visual and audible indicators.
Although there are many aerosol devices approved in the U.S., it is important that Ventavis be dosed only via the I-neb AAD System. Only the I-neb AAD System is currently available and has been FDA approved to deliver safe and accurate dosing of Ventavis.
Standard airjet nebulizers/compressors or ultrasonic nebulizer systems are continuous flow systems that constantly generate aerosol. Patients typically have a 40:60 inhalation:exhalation ratio; therefore, about 60% of the drug is wasted to the environment with such devices during exhalation.2 Additionally, a variable amount of drug is inhaled by each patient because individual breathing patterns differ (e.g., short, shallow breaths to long, deep breaths).
In contrast, Ventavis is a potent prostacyclin analogue which requires precise, reproducible dosing of Ventavis to every patient for the safety and efficacy of the drug. The I-neb AAD System only delivers the drug during the patient's inhalation and adapts for each patient's unique breathing pattern.
The I-neb AAD device is a compact, lightweight, battery-powered system that is approximately 6 inches high and weighs less than 8 ounces. Each patient is provided with one I-neb AAD System and a convenient carrying bag, complete with room for supplies.