Erythromycin nephrotoxicity

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

CICLOSPORIN MACROLIDES -CLARITHROMYCIN, ERYTHROMYCIN, TELITHROMYCIN t plasma concentrations of ciclosporin, with risk of nephrotoxicity, myelosuppression, neurotoxicity, excessive immunosuppression, with risk of infection and post-transplant lymphoproliferative disease Inhibition of CYP3A4-mediated metabolism of ciclosporin these inhibitors vary in potency. Clarithromycin and telithromycin are classified as potent inhibitors Avoid co-administration with clarithromycin and telithromycin. Consider alternative antibiotics but need to monitor plasma ciclosporin levels to prevent toxicity... 

Special attention is needed when new medications are prescribed to CSA-treated patients. CSA is extensively metabolized by the cytochrome P450 hver microsomal enzyme system [2, 3], and consequently drugs that interfere with this pathway can cause important changes in CSA blood levels (Table 3). Compounds inhibiting P450 enzymes, such as ketoconazole, erythromycin, verapamil, and diltiazem increase concentration of parent CSA and may cause acute nephrotoxicity. On the other hand, drugs that increase P450 enzyme activity, such as phenobarbital, carbamazepine and... 

Table 1. Some cytochrome P450 3A4 enzyme and P-glycoprotein efflux transporter inhibitors, inducers, and shared substrates with nephrotoxic potential. Inhibitors Inducers Substrates Erythromycin Amiodarine Cyclosporine ...

The oral administration of neomycin (usually in combination with erythromycin base) has been employed primarily for preparation of the bowel for surgery. For therapy of hepatic encephalopathy, a daily dose of 4 to 12 g (in divided doses) by mouth is given, provided that renal function is normal. Because renal insufficiency is a complication of hepatic failure and neomycin is nephrotoxic, it is used rarely for this indication. Lactulose is a much less toxic agent and is preferred. 

A study in 9 transplant patients taking ciclosporin found that erythromycin increased the mean trough serum levels of 3 kidney transplant patients sevenfold, from 147 to 1125 nanograms/mL, and of 6 heart transplant patients four- to fivefold, from 185 to 815 nanograms/mL. Acute nephrotoxicity occurred in all 9 patients, and 7 showed mild to severe hepatotoxicity caused by the increased ciclosporin levels. ... 

Direct information seems to be limited to these case reports. However, it would be prudent to closely monitor the effects of adding clarithromycin or erythromycin in any patient, being alert for the need to reduce the tacrolimus dosage to avoid nephrotoxicity. The manufaeturers prediet that josamycin and troleandomycin will internet similarly and so the same precautions would also be appropriate. The manufaeturers of telithromy-cin also recommend close monitoring of tacrolimus levels and reducing the tacrolimus dose as required. Most other maerolides would also be expected to interact although they do not all behave identically. 

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