Clarithromycin Ciclosporin

The macrolide antibacterials (including erythromycin, clarithromycin and telithromycin) are often implicated in interactions, most frequently as a result of inhibition of the CYP3A4 enzyme system in the liver and enterocytes. Erythromycin inhibits the metabolism of carbamazepine, ciclosporin and theophylline significant increases in serum levels and features of toxicity have been documented. Careful clinical and pharmacokinetic monitoring are required in a patient taking any of these drugs who requires concomitant erythromycin. 

The metabolism of ciclosporin is inhibited by diltiazem, verapamil, azole antifungal agents, erythromycin and clarithromycin with resultant potential for renal, hepatic and CNS toxicity. These interactions have been investigated as a cost saving device in organ transplant recipients, with the aim of using a lower dose of ciclosporin to achieve immunosuppression. 

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... 

Erythromycin increases ciclosporin blood concentrations, and increased serum creatinine concentrations have been consistently demonstrated isolated reports have also suggested possible interactions with clarithromycin, josamycin, midecamycin, or pristinamycin (SEDA-21, 385) (274). A two-fold increase in ciclosporin concentrations has been... 

In a study in 8 healthy subjects, ciclosporin 3.75 to 7.5 mg/kg was given alone and after they took clarithromycin 250 mg every 12 hours for 7 days. The maximum ciclosporin levels were raised by 50% by the clarithromycin. In another study a mean 30% reduction in the dosage of ciclosporin was needed in 6 transplant patients also given clarithromycin. Clarithromycin 500 mg twice daily as part of a Helicobacter pylori eradication regimen caused a two- to threefold increase in ciclosporin levels in 27 kidney transplant patients. The ciclosporin levels in 4 renal transplant patients with stable renal function increased by approximately 72% when clarithromycin 250 mg twice daily for 6 days was added to treat gingival hyperplasia. Ciclosporin levels returned to baseline levels within 7 days of stopping clarithromycin. Only two patients required a ciclosporin dose reduction. ... 

Numerous case reports also describe this interaction ciclosporin levels or AUC have been increased by two- to threefold, " with changes being seen within 3 to 6 days of clarithromycin 250 or 500 mg twice daily being started. " Another patient had a seven- to twelvefold rise in serum ciclosporin levels and acute renal failure within 3 weeks of starting to take clarithromycin 1 g daily. Another case report in a heart transplant patient taking ciclosporin found that the addition of rifampicin to clarithromycin negated the increase in ciclosporin levels seen with clarithromycin alone, and the ciclosporin dose requirement with concurrent clarithromycin plus rifampicin was similar to that before clarithromycin or rifampicin were started. ... 

Information about the interactions with clarithromycin, josamycin, mi-decamycin, and pristinamycin is much more limited, but they appear to behave like erythromycin. The same precautions should be taken. There seems to be no direct clinical information about telithromycin, trolean-domycin and rokitamycin but they would be expected to interact like erythromycin. Note that troleandomycin is usually a more potent inhibitor of CYP3A4 than erythromycin, so it may be expected to have a larger effect on ciclosporin levels. 

Three patients needed increases in the dosage of ciclosporin when given rifampicin and erythromycin, although the latter normally reduces ciclosporin requirements.Another patient whose ciclosporin levels had been raised by clarithromycin , (p.l016), had a fall in their levels when rifampicin was added... 

Drug-drug iuteractions Colchicine is metabolized by CYP3A4 and transported by P glycoprotein. It can therefore accumulate and have toxic effects during concomitant therapy with inhibitors of CYP3A4 and P glycoprotein, such as clarithromycin, disulfiram, and ciclosporin. Three such cases have been described [93, 94, 95 ]. 

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