Macrolides adverse reaction

Discuss ways to promote an optimal response to therapy, how to manage adverse reactions, and important points to keep in mind when educating patients about the use of a tetracycline, macrolide, or lincosamide. 

Discuss the uses, general drug action, adverse reactions, contraindications, precautions, and interactions of the tetracyclines, macrolides, and... 

Table 1 and Table 2 summarize the frequencies of adverse reactions and premature withdrawal of the most widely used macrolides. 

Table 1 Frequencies of adverse reactions to macrolide antibiotics...

Adverse reactions Erythromycin can cause nausea, vomiting, diarrhea, and abdominal cramping. Gl intolerance due to erythromycin is due to direct stimulation of the motilin receptor, leading to increased Gl motility. This occurs with both the IV and PO formulation. Although rare, all macrolides can cause hepatotoxicity. The estolate formulation of erythromycin has been associated with cholestatic hepatitis in pregnant women. In high doses, all macrolides can cause tinnitus. All macrolides can cause QT prolongation and torsade de points... 

Adverse effects might be produced when macrolides are administered with other medications. Here are potential adverse reactions ... 

Reports of macrolides causing adverse reactions in humans relate primarily to medicated stockfeed and parenteral formulations for injection. Farmworkers exposed to stockfeed medicated with spiramycin and tylosin have developed dermatitis and bronchial asthma. In addition, accidental needlesticks with needles contaminated with tilmicosin have caused minor local reactions, whereas accidental self-administration of injectable formulations of tilmicosin has resulted in serious cardiac effects and death. 

The documentation seems to be limited to the reports eited, but the interaction is established. Co-trimoxazole, sulfamethizole, sulfadiazine and trimethoprim can increase serum phenytoin levels. The interaction probably occurs in most patients, but the small number of adverse reaction reports suggests that the risk of toxicity is small. It is clearly most likely in those with serum phenytoin levels at the top end of the range. If concurrent use is thought appropriate, the serum phenytoin levels should be closely monitored and the phenytoin dosage reduced if necessary. Alternatively, if appropriate, use a non-interacting antibacterial (in some circumstances penicillins , (p.562), or macrolides , (p.560), may be appropriate). There seems to be no information about other sulfonamides but it would be prudent to be alert for this interaction with any of them. 

The use of macrolides in diffuse panbronchiolitis has been reviewed [69 ]. There was only one suitable randomized control trial that suggested benefit from prolonged macrolide therapy. No comment on adverse events was made. Several prospective open trials suggested benefit of long-term, low-dose macrolides without significant adverse reactions. 

In patients allergic to penicillin, a macrolide such as erythromycin or a first-generation cephalosporin such as cephalexin (if the reaction is nonimmunoglobulin E-mediated hypersensitivity) can be used. Newer mac-rolides such as azithromycin and clarithromycin are as effective as erythromycin and cause fewer GI adverse effects. 

The use of cisapride and its benefit to harm balance in children has been reviewed (25). Overall it is well tolerated. The most common adverse effects are diarrhea, abdominal cramps, borborygmi, and colic. Serious adverse events are rare and include isolated cases of extrapyramidal reactions, seizures in epileptic patients, cholestasis, QT interval prolongation and ventricular dysrhythmias, anorexia, and enuresis. Interactions of cisapride with other drugs are similar to those reported in adults. Co-administration of drugs that inhibit CYP3A4, such as imidazoles, macrolide antibiotics, the antidepressant nefazodone, and protease inhibitors such as ritonavir, are contraindicated. Furthermore, co-administration of anticholinergic drugs can compromise the beneficial effects of cisapride. 

Although the incidence of serious adverse effects to the macrolides is relatively low in animals, notable reactions do occur with some formulations and in certain animal species. For example, the irritancy of some parenteral... 

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