Incidence of nausea is dose-dependent: incidence of nausea was higher in people taking a larger dose (30%) versus placebo (10%) as compared to people taking a smaller dose (16%) versus placebo (11%). Depression and suicide
In 2007, the US FDA had announced it had received post-marketing reports of thoughts of suicide and occasional suicidal behavior, erratic behavior, and drowsiness among people using varenicline for smoking cessation. In 2009, the US FDA required varenicline to carry a boxed warning that the drug should be stopped if any of these symptoms are experienced.A 2014 systematic review did not find evidence of an increased suicide risk. Other analyses have reached the same conclusion and found no increased risk of neuropsychiatric side effects with varenicline. No evidence for increased risks of cardiovascular events, depression, or self-harm with varenicline versus nicotine replacement therapy was found in one post-marketing surveillance study.In 2016 the FDA removed the black box warning. People are still advised to stop the medication if they "notice any side effects on mood, behavior, or thinking." Cardiovascular disease
In June 2011, the US FDA issued a safety announcement that varenicline may be associated with "a small, increased risk of certain cardiovascular adverse events in people who have cardiovascular disease. "A prior 2011 review had found increased risk of cardiovascular events compared with placebo. Expert commentary in the same journal raised doubts about the methodology of the review, concerns which were echoed by the European Medicines Agency and subsequent reviews.
Clinical trial number NCT03636061 for "Clinical Trial to Evaluate the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease (The ONSET-1 Study)" at ClinicalTrials.gov
Clinical trial number NCT04036292 for "Evaluating the Efficacy and Safety of OC-01 (Varenicline) Nasal Spray on Dry Eye Disease" at ClinicalTrials.gov