RxPRODUCT NEWS: PROFILE: Ventavis (iloprost)

Pulmonary arterial hypertension (PAH) is a condition of high blood pressure in the pulmonary arteries of the lungs. The pulmonary arterial pressure is continuously elevated (defined as pressure >25 mm Hg at rest or >30 mm Hg with exercise).^1,2 PAH is illustrated by vascular changes?such as vasoconstriction, vascular proliferation/remodeling, and thrombosis formation?leading to compromised pulmonary circulation and increased oxygen demand.³ There is no cure, and, if left untreated, the disease can progress to right heart failure and potentially death.

Therapeutic considerations include anticoagulants, calcium channel blockers, endothelin-receptor antagonists, and prostacyclin therapy.³ CoTherix's Ventavis (iloprost) is the first inhaled prostacyclin in the United States that has been FDA-approved for PAH in patients with New York Heart Association (NYHA) Class III or IV symptoms.⁴

Pharmacology

A metabolite of arachadonic acid in vascular cells, prostacyclin (or prostaglandin I²) allows for the relaxation of vascular smooth muscle by stimulating cyclic adenosine monophosphate production and impeding smooth muscle cell growth.^2,3

Ventavis is a synthetic prostacyclin analogue that causes the dilation of systemic and pulmonary arterial vasculature.⁵

Clinical Trials

Ventavis was studied in a randomized, double-blind, multicenter, placebo-controlled trial involving 203 patients with severe PAH and chronic thromboembolic PAH (NYHA Class III or IV). The combined primary end point included an improvement of at least 10% in walking distance within 6 minutes, and improvement in the NYHA functional class versus baseline with no deterioration or death. Either Ventavis or placebo was added to patients'current therapy, which included vasodilators, anticoagulants, diuretics, and oxygen. Those receiving Ventavis were given 2.5-or 5-mcg doses by repeated inhalations 6 to 9 times per day. After 12 weeks of treatment, 17% of the patients taking the drug met the clinical end point, versus 5% receiving placebo (P = .007). In addition, there was improvement in the NYHA class (P = .03), in dyspnea (P = .015), and in quality of life (P = .026) with Ventavis, versus placebo.⁶

In an uncontrolled study, a total of 24 patients with NYHA Class III and IV PAH received Ventavis in addition to basic therapy. Participants received daily doses of Ventavis 100 or 150 mcg for at least 1 year. At the end of 12 months, there was significant improvement in mean pulmonary arterial pressure, cardiac output, stroke volume, mixed oxygen saturation, and pulmonary vascular resistance (P <.05).⁷

CoTherix currently is sponsoring a phase 2 randomized, double-blind, parallel-group, placebo-controlled trial, named the STEP trial.4 The results of this trial will be used to evaluate the safety and efficacy of Ventavis when it is added to patients'therapy that already includes the use of bosentan, an endothelin-receptor antagonist that prevents vasoconstriction of the vascular endothelium and smooth muscle.^4,8

Safety

Ventavis is generally well tolerated. Common side effects include flushing, coughing, mild jaw pain, headaches, syncope, and flu-like symptoms.^5,6 Increased dosages may result in more serious adverse events, including chest pain and discomfort.⁵ Caution should be used when administering Ventavis with vasodilators because there is a potential to increase the hypotensive effect. There also may be a risk for increased bleeding in patients maintained on anticoagulants. In clinical trials, however, Ventavis was used concomitantly with vasodilators and anticoagulants without reports of complications.^5,6 Caution also should be exercised with the elderly, pregnant and nursing mothers, and hepatically and renally impaired patients.⁵

Outlook

Overall, Ventavis appears to be safe and effective. It provides patients and physicians with a new inhaled, noninvasive option for PAH. Such an option should increase patient compliance, improve management of the disease, and avoid intravenous complications associated with invasive therapy. Ventavis Inhalation is available in cartons of 30 or 100 clear-glass single-use ampules (20 mcg/2 mL). It is stored at room temperature. The recommended dose of Ventavis is 2.5 mcg for the first inhalation and 5 mcg 6 to 9 times per day thereafter if the first dose is well tolerated.⁵

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist at Partners HealthCare System.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@mwc.com.