Erythromycin coadministration

Siedlik PH, Olson SC, Yang BB, Stern RH. Erythromycin coadministration increases plasma atorvastatin concentrations. J Clin Pharmacol 1999 39(5) 501 l. 

Siedlik, P.H., Olson, S.C.. Yang. B.B.. and Stern, R.H. (1999) Erythromycin coadministration increases plasma atorvastatin concentrations. Journal of Clinical Pharmacology, 39, 501-504. 

CYP3A4 enzyme. A clinical study has shown that coadministration of eletriptan with ketoconazole, erythromycin, verapamil, and fluconazole increased the Cmax3> cl... 

Clozapine is metabolized by hepatic CYP 1A2 and, to a lesser degree, CYP 3A3/4 therefore, the drug is subject to changes in serum concentration when combined with medications that inhibit or induce these enzymes. Serum clozapine levels increase with coadministration of fluvoxamine or erythromycin and decrease with coadministration of phenobarbital or phenytoin and with cigarette smoking (Byerly and DeVane 1996). These pharmacokinetic interactions are particularly important because of the dose-dependent risk of seizures. 

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Triazolam plasma concentrations were determined by gas chromatography with electron capture detection (73,95). The pharmacokinetic results demonstrated that mean clearance during Trials B and C were nearly identical (413 and 416 mL/min, respectively) that is, coadministration of azithromycin had no effect on the pharmacokinetics of triazolam (Fig. 5). However, triazolam clearance was significantly reduced to 146 mL/min by erythromycin (Trial D) and to 95 mL/min by clarithromycin (Trial E). Thus, the in vivo kinetic results are highly consistent with the in vitro data. 

The pharmacodynamic data indicated that the benzodiazepine agonist effects of triazolam plus placebo (Trial B) and of triazolam plus azithromycin (Trial C) were similar to each other and greater than the effects of placebo plus placebo (Trial A). However, coadministration of erythromycin (Trial D) or... 

Advanced cases may require coadministration of ampicillin or erythromycin. 

The association of ventricular dysrhythmias with coadministration of erythromycin and terfenadine (58) is thought to be due to inhibition of CYP3A4 by erythromycin. This combination should be avoided. 

Telithromycin has several clinically significant drug interactions similar to those for erythromycin. It is both a substrate and a strong inhibitor of CYP3A4. Coadministration of rifampin, a potent inducer of CYP, decreases the serum concentrations of telithromycin by 80%. CYP3A4 inhibitors (e.g., itraconazole) increase peak serum concentrations of telithromycin. Serum concentrations of CYP3A4 substrates (e.g., pimozide, cisapride, midazolam, statins, cyclosporine, phenytoin) are increased by telithromycin. Telithromycin also increases peak serum concentrations of metoprolol and digoxin. 

Despite decades of clinical availability and coadministration of erythromycin with theophylline-containing compounds, the nature, extent, and severity of this potentially serious metabolic drug-drug interaction was not immediately recognized. Recently, however, erythromycin drug-drug interactions have been extensively studied and are now well recognized (see Section III). 

Yamreudeewong W, Scavaie I one RP, Lewis GP Effect of antacid coadministration on the bioavailability of erythromycin stearate. Cbn Pharm ( 9Z9) 8, 352-4. 

GouldenKJ, CamfieldP, Dooley JM,Fraser A, Meek DC, Renter KW, Tibbies JAR. Severe carbamazepine intoxication after coadministration of erythromycin. J Pediatr (1986) 109, 135-8. 

Sale M, Lyness W, Perhach J, Woosley R, Rosenberg A. Lack of effect of coadministration of erythromycin (ERY) with azelastine (AZ) on pharmacokinetics (PK) or... 

Hourmant M, Le Bigot JF, Vemillet L, Sagniez G, Remi JP, Soulillou JP. Coadministration of erythromycin results in an increase of blood cyclosporine to toxic levels. Transplant Proc (1985) 17, 2723-7,... 

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