Macrolide antibacterials. Drug interactions of clinical significance.

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von Rosensteil NA, Adam D

Macrolide antibacterials. Drug interactions of clinical significance.

Drug Saf. 1995 Aug;13(2):105-22.

PubMed ID

7576262 [ View in PubMed

]

Abstract

Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Midecamycin	Cytochrome P450 3A4	Protein	Humans	No	Substrate Inhibitor	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Alfentanil Erythromycin	The serum concentration of Alfentanil can be increased when it is combined with Erythromycin.
Alfentanil Josamycin	The serum concentration of Alfentanil can be increased when it is combined with Josamycin.
Alfentanil Dirithromycin	The serum concentration of Alfentanil can be increased when it is combined with Dirithromycin.
Alfentanil Telithromycin	The serum concentration of Alfentanil can be increased when it is combined with Telithromycin.
Alfentanil Solithromycin	The serum concentration of Alfentanil can be increased when it is combined with Solithromycin.