Terfenadine Alcohol

Dyspepsia is the most common side effect of zileuton. Liver transaminase levels are elevated in a small percentage of patients taking zileuton. Serum Uver transaminase levels should be monitored and treatment halted if significant elevations occur. Zileuton inhibits the metabolism of theophylline. Thus, when these agents are used concomitantly, the dose of theophylline should be reduced by approximately one-half, and plasma concentrations of theophylline should be monitored closely. Caution should also be exercised when using zileuton concomitantly with warfarin, terfenadine, or propranolol, as zileuton inhibits the metabolism of these agents. Zileuton is contraindicated in patients with acute liver disease and should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease. 

Moser L, Huther KJ, Koch-Weser J, Lundt PV. Effects of terfenadine and diphenhydramine alone or in combination with diazepam or alcohol on psychomotor performance and subjective feelings. Eur J Clin Pharmacol 1978 14(6) 417-23. 

Bhatti JZ, Hindmarch I. The effects of terfenadine with and without alcohol on an aspect of car driving performance. Clin Exp Allergy 1989 19(6) 609-11. 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

P450 enzyme inhibition by SSRIs may also augment effects of alcohol, tramadol, methadone, terfenadine (danger of cardiac arrhythmia), -caine anaesthetics and theophylline. 

Cohen AF, Hamilton MJ, Peck AW. The effects of acrivas-tine (BW825C), diphenhydramine and terfenadine in combination with alcohol on human CNS performance. Eur J Clin Pharmacol 1987 32(3) 279-88. 

In a comparison of cetirizine and loratadine, cetirizine 10 mg had acute sedative effects and impaired driving performance (65), whereas loratadine had no sedating potential furthermore, there was an additive effect of alcohol and cetirizine but not alcohol and loratadine. However, in a study using a driving simulator cetirizine 10 mg did not affect driving ability (66). In other studies cetirizine 20 mg caused significant sedation, while in one study there was a dose-dependent sedative effect with 10 mg and 20 mg but not 5 mg (67). Pooling the available data (SEDA-16, 163) shows that cetirizine is little more sedative than loratadine and terfenadine. 

The stabilization of benzylic radical and cation makes homolytic or heterolytic fragmentation at the benzylic position a common occurrence in the photochemistry of these derivatives C-H and C-C fragmentation take place (Scheme 4.29). An example of the first case is the oxidation of the alcohol function to ketone in the anthistaminic drug terfenadine (44 dehydration to form a conjugated alkene also takes place, Scheme 4.30) (Chen et al., 1986). Another is the oxidation of a CH2 to... 

Terfenadine is contraindicated in patients with impaired hepatic function (for example, alcoholic cirrhosis, hepatitis)... 

Unlike other antihistamines, terfenadine has minimal anticholinergic activity and does not potentiate the CNS effects of alcohol, antianxiety agents, or other CNS depressants. 

Buspirone does not appear to interact with amitriptyline, cimetidine or terfenadine. An isolated report describes mania when an alcoholic patient taking huspirone was given disulfiram. Nefazodone greatly increases huspirone levels. 

HAM of substituted allyl alcohols results in biologically active tertiary amines, such as ibutilide and aripiprazole (Scheme 5.118) [57]. Protection of the allylic hydroxyl group was found to be unnecessary no lactol formation was observed during the hydroformylation step. The antihistamines terfenadine and fexofenadine were prepared in the same manner [102]. 

Fexofenadine, as the carboxylic analogue of terfenadine, is an amino acid with a highly hydrophilic zwitterionic stmcture. Its enantiomers have been separated repeatedly by chromatographic methods [9, 17, 18], and the CD spectra reveal a positive extreme for the f -(+)-enantiomer at 205 nm with a shoulder at 225 nm. The absolute configuration of the fexofenadine enantiomers was determined by chemical correlation with the alcohol S-(-)-12, for which the prediction of absolute configuration is based on the configuration of the chiral catalysts used in reduction. Details are presented in Scheme 10.9. 

It was found that the fungus, C. blakesleeana, was not able to perform the complete oxidation of terfenadine to fexofenadine, because the reactimi stopped at the level of the prim-alcohol. Since the prim-alcohol cannot be selectively oxidized with strong agents, such as RuCls or HslOe, but rather this occurs with the secondary hydroxy group, the result was disappointing for the scale-up process. 

Further progress was made by Buisson et al. [40]. These authors screened a series of micro-organisms for their abiUty to oxidize the ieri-butylphenyl group in terfenadine. They defined the culture conditions required to increase the formation of the carboxylic acid and to avoid the formation of alcohols and other side products. Table 10.4 shows the products detected in crude extracts after 96 h incubation [40]. 

Micro-organisms Culture medium Terfenadine Fexofenadine Alcohol... 

---