Ciclosporin Amiodarone

AMIODARONE CICLOSPORIN Cidosporin levels may be t by amiodarone risk of nephrotoxicity Uncertain cidosporin is metabolized by CYP3A4, which is markedly inhibited by amiodarone. Amiodarone also interferes with renal elimination of cidosporin and inhibits intestinal P-gp, which may T the bioavailability of cidosporin Monitor renal function closely consider reducing the dose of cidosporin when co-administering amiodarone... 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

Citrus flavinoids in grapefruit (but not orange) juice decrease hepatic metaboUsm and may lead to risk of toxicity from amiodarone, terfenadine (cardiac arrhythmia), benzodiazepines (increased sedation), ciclosporin, felodipine (reduced blood pressure). 

Amiodarone can increase the blood concentrations of ciclosporin and thus impair renal function. 

A 66-year-old developed a ventricular tachycardia after kidney transplantation and was given amiodarone. Maintenance immunosuppression included prednisone, azathioprine, and ciclosporin. Ciclosporin concentrations before amiodarone initiation were stable (range 100-150 ng/ml). During amiodarone therapy, the ciclosporin concentration increased more than two-fold. 

Mibefradil inhibits CYP3A4 (2). Other drugs that are metabolized by this pathway accumulate as a result. Drugs that were commonly affected included amiodarone, astemizole, ciclosporin, cisapride, erythromycin, imi-pramine, lovastatin, propafenone, quinidine, simvastatin (9), tacrohmus (10), tamoxifen, terfenadine, thioridazine, and drugs that impair sinoatrial node function (for example beta-blockers) (6). 

Ciclosporin serum levels can be increased or decreased by amiodarone, and nephrotoxicity has occurred as a result of increased levels. Increased amiodarone levels and pulmonary toxicity have been reported in patients also given ciclosporin. 

In contrast, in 5 heart transplant patients amiodarone was discontinued and ciclosporin initiated, but the metabolism of ciclosporin was increased for 4 to 5 weeks (total plasma metabolites increased from 720 to 1437 nanograms/mL). The mean maintenance ciclosporin level was reduced by 15 nanograms/mL. ... 

In two heart transplant patients who had stopped amiodarone and started ciclosporin an increase in the plasma levels of amiodarone and its main metabolite, desethylamiodarone, was seen for 4 to 5 weeks. During this period increased adverse effects, including pulmonary toxicity, were... 

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