Erythromycin intravenous administration

Intravenous antibiotic administration is the most common delivery method for surgical prophylaxis. Intravenous administration ensures complete bioavailability while minimizing the impact of patient-specific variables. Oral administration is also used in some bowel operations. Non-absorbable compounds like erythromycin base and neomycin are given up to 24 hours prior to surgery to cleanse the bowel. Note that oral agents are used adjunctively and do not replace IV agents. 

The incidence of side effects associated with erythromycin therapy is very low. Mild gastrointestinal upset with nausea, diarrhea, and abdominal pain are reported to occur more commonly when the propionate and es-tolate salts are used. Rashes are seen infrequently but may be a part of a general hypersensitivity reaction that includes fever and eosinophilia. Thrombophlebitis may follow intravenous administration, as may transient impairment of hearing. 

Administration The erythromycin base is destroyed by gastric acid thus either enteric coated tablets or esterified forms are administered. All are adequately absorbed on oral administration. Clarithromycin and azithromycin are stable to stomach acid and are readily absorbed. Food interferes with the absorption of erythromycin and azithromycin but can increase that of clarithromycin. Intravenous administration of erythromycin is associated with a high incidence of thrombophlebitis. 

Intravenous administration of erythromycin into peripheral veins relatively commonly causes thrombophlebitis, although the lactobionate form of erythromycin may be less irritating to veins than other parenteral forms (11,12). In a prospective study of 550 patients with 1386 peripheral venous catheters, the incidence of phlebitis was 19% with antibiotics and 8.8% without erythromycin was associated with an increased risk (13). 

The effects of erythromycin, an inhibitor of CYP3A4, on the pharmacokinetics of lidocaine have been studied in nine healthy volunteers. Steady-state oral erythromycin had no effect on the plasma concentration versus time curve of lidocaine after intravenous administration, but erythromycin increased the plasma concentrations of the major metabolite of lidocaine, MEGX (78). It is not clear what the interpretation of these results is, particularly since the authors did not study enough subjects to detect what might have been small but significant changes in various disposition parameters of lidocaine and did not report unbound concentrations of Udocaine or its metabolites. However, whatever the pharmacokinetic explanation, the clinical relevance is that one would expect that erythromycin would potentiate the toxic effects of lidocaine that are mediated by MEGX. 

Patients presenting with acute erythromycin overdose are usually asymptomatic or experiencing minor to moderate gastrointestinal side effects/ discomfort. Serious cardiac effects, including prolongation of the QT interval, arrhythmias (i.e., ventricular tachycardia. Torsades de Pointes, ventricular fibrillation, and heart block), may be observed after rapid intravenous administration and coincident with high, peak erythromycin plasma concentrations. The occurrences of these QT prolongation-associated arrhythmias are rare. 

Fig. 4. Whole-body autoradiograms showing the distribution of radioactivity 5 min after intravenous administration of C-clarithromycin (TE-031) and C-erythromycin (EM) (5 mg/kg) to rats. (From Kohno et al. [60], Fig, 2, p. 754.)...

What serious adverse effect is caused by intravenous administration of erythromycin ... 

Absorption Erythromycin base is incompletely but adequately absorbed from the upper small intestine. Because it is inactivated by gastric acid, the drug is administered as enteric-coated tablets, as capsules containing enteric-coated pellets that dissolve in the duodenum, or as an ester. Food may impair absorption. Esters of erythromycin base e.g., stearate, estolate, and ethylsuccinate) have improved acid stability and are less affected by food. Higher erythromycin concentrations can be achieved by intravenous administration. 

The terminal half-life of erythromycin A in calves and adult cows is relatively short (2.9-4.1 h) after intravenous administration, but much longer after intramuscular (11.9 h) or subcutaneous (18.3 to 26.9 h) dosing, as a consequence of flip-flop pharmacokinetics of commercially available formulations, that is, of a very slow process of drug... 

Acid-addition salts with hydrophilic acids are water-soluble forms of erythromycin for intravenous administration. The lactobionate and glucep-... 

Oleandomycin is a macrolide antibiotic produced by Streptomyces antibi-oticus. Oleandomycin and its triacetylated form, troleandomycin, are less effective than erythromycin against staphylococcal infections. They are usually administered orally or intravenously intramuscular administration is avoided because of the pain and tissue irritation it induces. Oleandomycin is also used in intramammary treatments and as a feed additive for growth promotion purposes. 

Ingestion is the most common route of both accidental and intentional exposures to erythromycin. Numerous erythromycin salt preparations are available in tablet, capsule, or liquid preparations for oral administration. Other available forms include intravenous, topical (acne), and ophthalmic preparations. 

In contrast, in 6 healthy subjeets erythromycin 500 mg twice daily for 7 days did not to affect the pharmaeokinetics of intravenous sufentanil 3 micrograms/kg in the 9 hours following administration. Two of the subjects were the same as those who had shown an alfentanil/erythromy-cin interaction cited above. 

In a study, 9 healthy subjects were given fluvoxamine 100 mg daily alone or with erythromycin 500 mg three times daily for 5 days before the administration of a single intravenous dose of lidoeaine 1.5 mg/kg on day 6. The clearance of lidoeaine was reduced 41% by fluvoxamine and 53% by concurrent fluvoxamine and erythromycin. ... 

In a similar study, erythromycin had no effect on the AUC or peak plasma level of a single 1.5-mg/kg intravenous dose of lidoeaine, but still increased the AUC of MEGX by 70%. In yet another study, erythromycin ethylsuccinate 600 mg three times daily for 5 doses had a minor effect on the pharmacokinetics of a single 1-mg/kg intravenous dose of lidoeaine (an 18% decrease in clearance), and caused a 33% increase in the AUC of MEGX. There was no difference in the results from the 10 healthy subjects and the 20 patients with biopsy proven cirrhosis. In another study, 9 healthy subjects were given fluvoxamine 100 mg daily alone or with erythromycin 500 mg three times daily for 5 days before the administration of a single intravenous dose of lidoeaine 1.5 mg/kg on day 6. The elearanee of lidoeaine was reduced 41% by fluvoxamine and 53% by concurrent fluvoxamine and erythromycin. ... 

The interaction between ciclosporin and erythromycin is well documented, well established and potentially serious. If concurrent use is thought appropriate, monitor the ciclosporin blood levels closely and reduce the dosage appropriately. A reduetion of about 35% has been calculated to be necessary The dosage should be inereased again when the erythromycin is stopped. The effect of intravenous erythromycin is less than oral erythromycin so if the route of administration is changed, be alert for the need to change the ciclosporin dosage. ... 

Development of bacterial resistance, with associated cross-resistance to lin-comycins, may occasionally limit the clinical use of the macrolides. The esters formed by these antibiotics are clinically important because they are more readily absorbed from the intestinal tract, but are possibly more toxic. Erythromycin is commonly administered orally as a base, stearate, or as an estolate, but it can also be administered intravenously as a lactobionate or glucoheptonate or intramuscularly as an ethylsuccinate, although such administration is rare, because the injec-... 

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