In controlled and uncontrolled clinical trials involving more than 5000 patients treated with ZYFLO, the overall rate of ALT elevation ≥ 3xULN was %. In these trials, one patient developed symptomatic hepatitis with jaundice , which resolved upon discontinuation of therapy. An additional 3 patients with transaminase elevations developed mild hyperbilirubinemia that was less than three times the upper limit of normal. There was no evidence of hypersensitivity or other alternative etiologies for these findings. In subset analyses, females over the age of 65 appeared to be at an increased risk for ALT elevations. Patients with pre-existing transaminase elevations may also be at an increased risk for ALT elevations (see CONTRAINDICATIONS ).
Safety and efficacy have not been established. However, pediatric patients commonly receive dosing as in product labels: 1 to 2 drops in the affected eye(s) 2 to 4 times daily or 2 drops in the affected eye(s) 4 times per day. During the initial 24 to 48 hours, may increase dose frequency if necessary. If signs and symptoms fail to improve after 2 days, re-evaluate. Once the condition is responding, lower dosage may be used, but care should be taken not to discontinue therapy prematurely. In chronic conditions, withdrawal of treatment should be carried out by gradually decreasing the frequency of applications.
Two small trials recruiting 23 participants met the inclusion criteria for the review . Participants may have been suffering from comorbid lung disease. No data on oral steroid consumption were reported. No significant differences were observed in the studies for FEV 1 , FVC, PaO 2 and symptoms. One study reported a statistically significant difference in SGaw, but the clinical importance of this is uncertain. Due to concerns over the small sample sizes and methodological shortcomings in terms of inadequate washout in one study , and methods used in outcome assessment for both studies, the findings of the studies are not generalisable to the issue of steroid tapering. An update search conducted in August 2010 did not identify any new studies for consideration in the review .