Drug Interactions between Decadron with Xylocaine and Estragyn 5

MONITOR: Estrogens may enhance the systemic effects of both endogenous and exogenous corticosteroids. The proposed mechanism is an increase in serum cortisol-binding globulin (transcortin) induced by estrogens, resulting in a decreased rate of corticosteroid metabolic clearance. The interaction has been reported with estrogens or estrogen-containing oral contraceptives (OCs) and hydrocortisone, prednisone, and prednisolone. In one pharmacokinetic study, the mean plasma clearance of total prednisolone (40 mg IV) in eight female OC users was less than half that of five healthy female non-OC users and eight healthy males, and the prednisolone half-life and mean residence time were longer. There was also a 2-fold increase in the area under the plasma concentration-time curve for unbound prednisolone compared to controls.

MANAGEMENT: Patients treated concomitantly with an estrogen-containing drug may require lower dosages of corticosteroids or adrenocorticotropic agents. Pharmacologic response to these agents should be monitored more closely whenever an estrogen is added to or withdrawn from therapy in patients stabilized on their existing corticosteroid or adrenocorticotropic regimen, and the dosage(s) adjusted as necessary.

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Coadministration with inducers of CYP450 1A2 and/or 3A4 may decrease the plasma concentrations of lidocaine, which is primarily metabolized by these isoenzymes. In four healthy volunteers (2 smokers and 2 nonsmokers), administration of a single 400 mg oral dose of lidocaine following pretreatment with the CYP450 inducer phenobarbital (15 mg/day for 4 weeks, followed by 30 mg/day for 4 weeks) decreased lidocaine systemic exposure (AUC) by 37% and increased its oral clearance by 56% compared to administration of lidocaine alone. In another study, the mean bioavailability of a single 750 mg oral dose of lidocaine in six patients receiving chronic antiepileptic drug therapy (consisting of one or more of the following enzyme-inducing anticonvulsants: phenobarbital, primidone, phenytoin, carbamazepine) was approximately 2.5-fold lower than that reported for six healthy control subjects, while intrinsic clearance was nearly threefold higher. By contrast, the interaction was modest for lidocaine administered intravenously, suggesting induction of primarily hepatic first-pass rather than systemic metabolism of lidocaine. When a single 100 mg dose of lidocaine was given intravenously, mean lidocaine AUC was reduced by less than 10% and serum clearance increased by just 17% in the epileptic patients compared to controls. These changes were not statistically significant. Likewise, mean lidocaine AUC decreased by approximately 11% and plasma clearance increased by 15% when a single 50 mg intravenous dose of lidocaine was administered following pretreatment with the potent CYP450 inducer rifampin (600 mg/day for six days) in ten healthy, nonsmoking male volunteers. Another pharmacokinetic study found that cigarette smoke, an inducer of CYP450 1A2, reduced the bioavailability of lidocaine when administered orally, but had only minor effects on lidocaine administered intravenously. When 4 smokers and 5 non-smokers received 2 doses of lidocaine (100 mg IV followed by 100 mg orally after a 2-day washout period), the smoker's systemic exposure (AUC) of oral lidocaine was 68% lower than non-smokers. The AUC of IV lidocaine was only 9% lower in smokers compared with non-smokers. The clinical impact of smoking on lidocaine has not been studied, however, a loss of efficacy may occur.

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Coadministration with estrogens may increase or decrease the plasma concentrations and effects of lidocaine. Estrogen can reduce alpha-l-acid glycoprotein (AAG), a plasma protein to which lidocaine has a relatively high binding affinity. Theoretically, a reduction in AAG could result in a higher free fraction of lidocaine, though clinical reports of adverse reactions resulting from this effect do not currently exist. In contrast, a pharmacokinetic study of postmenopausal women on oral hormone therapy (HT) highlighted the opposite effect. Study subjects received oral or transdermal HT with 17-beta-estradiol and micronized progesterone for 6 months with single intravenous lidocaine doses (1 mg/kg) prior to, at 3 months, and at 6 months of HT. At 3 months, lidocaine plasma exposure (AUC) and half-life were reduced by 15% and 15.2%, respectively. Additionally, lidocaine's elimination rate constant increased by 10%. However, no changes in lidocaine's AUC, half-life, or elimination rate constant were observed at 6 months with oral HT or at any point with transdermal HT. The mechanism and clinical significance are not clear, nor is the contribution, if any, of progesterone to this interaction. Clinical and laboratory monitoring may be advised when estrogen-containing products are coadministered with lidocaine.

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