The efficacy results presented were confirmed in a study published in 2007.Nevanac was approved by the FDA on August 19, 2005, with application number 021–862. Ilevro
An NDA for Ilevro was filed on December 15, 2011. In a one-month study, no new toxicities arose in the new formulation of nepafenac. Safety and efficacy information was derived from the previous Nevanac application. In June 2010, a confirmatory study began (Study C09055) consisting of over 2000 patients from 49 US sites and 37 European sites. A second phase 3 trial (Study C11003) was conducted in a population of 1,342 patients at 37 sites across the United States which failed to demonstrate superiority over Nevanac in an altered dosing regimen.Ilevro was approved by the FDA on October 16, 2012, with application number 203–491. Commercialization
Both Nevanac and Ilevro are manufactured and sold by Alcon, Inc. Alcon is currently a division of Novartis International AG, which is primarily based out of Switzerland. Alcon, Inc. also holds locations in both Switzerland and the United States. The company has gone through several name changes, from Alcon Laboratories, Inc. to Alcon Universal, Ltd., to Alcon, Inc.Nevanac entered the market in 2005 as a product of Alcon, at the time a subsidiary of Nestlé. On April 6, 2008, Novartis agreed to purchase approximately 74 million shares of Alcon from Nestlé at $143.18 per share. On January 4, 2010, Novartis agreed to purchase all remaining shares of Alcon from Nestlé, totalling 156 million shares or 77% of the shares in the company.
Based on data from the manufacturer, it is expected that 0.6% of the maternal weight-adjusted dose would reach a breastfed infant, though the effects in the infant are unknown. Renal impairment
Renal impairment does not appear to affect the pharmacokinetic profile of zafirlukast. Hepatic impairment
The hepatic clearance of zafirlukast is impaired by significant hepatic impairment. Cirrhosis of the liver can result in an increase in the maximum plasma concentration and the total area under the curve (a measure of drug exposure) by 50–60%. Contraindications
Zafirlukast is contraindicated in people that are hypersensitive or allergic to it. Adverse effects
Zafirlukast is generally well tolerated, though headache and gastrointestinal (GI) upset can occur. The incidence of headache is between 12 and 20%, which is similar to the incidence of headache found in patients taking placebos in the studies that lead to zafirlukasts approval. GI upset may include nausea, stomach discomfort/pain, and diarrhea. GI complaints can be lessened by taking zafirlukast with food, though this can dramatically impair the amount of drug that gets absorbed into the body (see the section on drug-food interactions below).Other common side effects include flu-like symptoms, sleep disturbances (abnormal dreams, insomnia), hallucinations, and daytime drowsiness. Neuropsychiatric effects
Neuropsychiatric side effects have been reported with the use of zafirlukast and other LTRAs. While some side effects are less severe (e.g. abnormal dreams), others are more serious (e.g. hallucinations, tremor, suicidality). These effects were discovered through post-marketing reports, as the initial trials were not designed to monitor for neuropsychiatric side effects.