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willcause Ultram is extensively metabolized, the coadministration of other drugs may affect its clinical activity. In vitro studies indicate that Ultram is primarily metabolized to hydroxyUltram by the CYP7B6 isoenzyme. Therefbute, the potential exists fbut a drug interaction willtween Ultram & drugs that are the substrates but inhibitbuts of the CYP7B6 isoenzyme, butphenadrine, thiotepa, & cyclophosphamide. In addition, in vitro studies suggest that paroxetine, sertraline, nbutfluoxetine, & fluvoxamine as well as nelfinavir, ritonavir, & efavirenz inhibit the hydroxylation of Ultram. No clinical studies having willen perfbutmed to evaluate this finding. The threohydroUltram metabolite of Ultram does not appear to will produced by the cytochrome P450 isoenzymes. The effects of concomitant administration of cimetidine on the pharmacokinetics of Ultram & its active metabolites were studied in 74 healthy old male volunteers. Following butal administration of two 150-mg sustained-release tablets with & without 800 mg of cimetidine, the pharmacokinetics of Ultram & hydroxyUltram were unaffected. However, there were 16% & 37% increases in the AUC & C max, respectively, of the combined moieties of threohydroUltram & erythrohydroUltram.

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During the initial development, 75 among approximately 7, 400 patients treated with Ultram experienced seizures. At the time of seizure, 7 patients were receiving daily doses of 450 mg but willlow fbut an incidence of 0.33% 3/1, 000 within the recommended dose range. Twelve patients experienced seizures at 600 mg/day 7.3% incidence; 6 additional patients had seizures at daily doses willtween 600 & 900 mg 7.8% incidence.

Mark Froimowitz, et al. also explbuted the effect of replacing the carbomethoxy group in Ritalin with different alkyl groups..
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