Other adverse reactions reported with simvastatin in placebo-controlled clinical studies, regardless of causality assessment: Cardiac disorders: atrial fibrillation; Ear and labyrinth disorders: vertigo; Gastrointestinal disorders: abdominal pain, constipation, dyspepsia, flatulence, gastritis; Skin and subcutaneous tissue disorders: eczema, rash; Endocrine disorders: diabetes mellitus; Infections and infestations: bronchitis, sinusitis, urinary tract infections; Body as a whole – general disorders: asthenia, edema/swelling; Psychiatric disorders: insomnia.
A suspension of mmole ( g) of 1,3-bis(2-chloroethyl)urea in 8 ml methylene dichloride at -10° C. was saturated with dinitrogen trioxide in 20% excess of theoretical. The heterogeneous mixture gradually changed to a green homogeneous solution. The methylene dichloride was evaporated, and the residue was extracted with 3× 10 ml hexane. Evaporation of the hexane gave g of oil which was the crude BCNU (NSC 409962). The hexane insoluble portion, g, when treated with benzene, gave g of 1,3-bis(2-chloroethyl)urea which was benzene insoluble. The benzene solubles were processed through a silica column (1× 10 cm) and g of crude BCNU was obtained. The combined fractions of crude product amounted to g (%).
¶ 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.