Antibacterials drug interactions

Von Rosensteil NA, Adam D. Macrohde antibacterials. Drug interactions of chnical sigiuficance. Drug Saf 1995 13(2) 105-22. 

Von Rosenstiel, N. A., and Adam, D. (1995). Macrolide antibacterials Drug interactions of clinical significance. Drug Safety 13, 105-122. 

This section deals with interactions where the effects of the antibacterial are altered. In many cases the antibacterial drugs interact by affecting other drugs, and these interactions are dealt with elsewhere in this publication. Some of the macrolides and the quinolones are potent enzyme inhibitors the macrolides exert their effects on the cytochrome P450 isoenzyme CYP3A4, whereas many quinolones inhibit CYP1A2. Ri-fampicin (rifampin) is a potent non-specific enzyme inducer and therefore lowers the levels of many drugs. 

Kang, J., Wang, L., Chen, X.L., Higgle, D.J. and Rampe, D. (2001) Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG. Molecular Pharmacology, 29, 122-126. 

Tegretol consists of carbamazepine, which is an anti-epileptic drug. There is a clinically significant drug interaction between carbamazepine and clarithromycin (macrolide antibacterial agent) resulting in higher plasma concentrations of carbamazepine. 

La.4. Pharmacokinetics, i.e. Interaction between the Host and the Antibacterial Drug... 

Clarithromycin is metabolized in the liver. The major metabolite is 14-hydroxyclarithromycin, which also has antibacterial activity. A portion of active drug and this major metabolite is eliminated in the urine, and dosage reduction (eg, a 500-mg loading dose, then 250 mg once or twice daily) is recommended for patients with creatinine clearances less than 30 mL/min. Clarithromycin has drug interactions similar to those described for erythromycin. 

Stockley IH. Antibacterial and anti-infective agent drug interactions. In Stockley IH, ed. Stockley s drug interactions. 6th ed. London Pharmaceutical Press 2002. p. 128-232. 

Penning-van Beest FJ, van Meegen E, Rosendaal FR, Strieker BH. Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs. Clin Pharmacol Ther 2001 69(6) 451-7. 

Brouwers JR. Drug interactions with quinolone antibacterials. Drug Saf 1992 7(4) 268-81. 

Drug interactions with sulfonylureas and biguanides are common non-steroidal antiinflammatory drugs, warfarin, alcohol, monoamine oxidase inhibitors, some uricosurics, some antibacterials and some antifungals can interact with them. All increase the risk of hypoglycaemia. The mechanism is probably competition for metabolizing enzymes or displacement from plasma protein binding sites. 

A common drug interaction that occurs with the use of antimicrobial drugs, particularly drugs that have a wide antibacterial spectrum of activity, is... 

An established and clinically relevant metabolic drug interaction. The dosage of oral propafenone will need increasing during concurrent use of ri-fampicin. Alternatively, if possible, the authors of the case report advise the use of another antibacterial, where possible, because of the probable difficulty in adjusting the propafenone dosage. 

The known potential for quinolones to induce seizures suggests that these antibacterials should either be avoided in epileptics, or only used when the benefits of treatment outweigh the potential risks of seizures. Some of the reactions seem to be drug-disease interactions rather than drug-drug interactions, the usual outcome being that the control of epilepsy is worsened. However, it appears that ciprofloxacin may also alter (usually decrease) phenytoin levels, and if this combination is used it would be prudent to consider monitoring phenytoin levels. Enoxacin appears not to alter phenytoin levels. 

---