¶ Dose reduction and/or serum Theophylline concentration measurement is indicated whenever adverse effects are present, physiologic abnormalities that can reduce Theophylline clearance occur (., sustained fever), or a drug that interacts with Theophylline is added or discontinued (see WARNINGS ).
Once-Daily Dosing: The slow absorption rate of this preparation may allow once-daily administration in adult non-smokers with appropriate total body clearance and other patients with low dosage requirements. Once-daily dosing should be considered only after the patient has been gradually and satisfactorily titrated to therapeutic levels with q12h dosing. Once-daily dosing should be based on twice the q12h dose and should be initiated at the end of the last q12h dosing interval. The trough concentration (C min ) obtained following conversion to once-daily dosing may be lower (especially in high clearance patients) and the peak concentration (C max ) may be higher (especially in low clearance patients) than that obtained with q12h dosing. If symptoms recur, or signs of toxicity appear during the once-daily dosing interval, dosing on the q12h basis should be reinstituted.
It is essential that serum Theophylline concentrations be monitored before and after transfer to once-daily dosing.
Food and posture, along with changes associated with circardien rhythm, may influence the rate of absorption and / or clearance rates of Theophylline from extended-release dosage forms administered at night. The exact relationship of these and other factors to nighttime serum concentrations and the clinical significance of such findings require additional study. Therefore, it is not recommended that Theophylline extended-release once-daily dosing be administered at night.
BIs exposed to a sterilant that results in a quantal-zone outcome demonstrate more variability than unexposed BIs but also show a low frequency of BIs with a prolonged grow-out time. The MIT method proposed in this paper using the CST sterilization exposure takes into account this increased variability but properly avoids the occurrence and inappropriate influence of “outlier” results. In contrast, an unforeseen consequence of the 30-80% survival window of the FDA CDRH protocol is that the RIT is driven by the outlier results of large percentages of BIs having only a single spore. This effect can be seen in the fact that a shorter incubation time can be achieved if the average nonsterile results are closer to 80% versus 30%, which is a result attributed to the difference in the fraction of nonsterile BIs having only a single surviving spore. This consequence is clearly undesirable for a test method and demonstrates a lack of robustness and reproducibility.