Ciclosporin Amlodipine

CALCIUM CHANNEL BLOCKERS CICLOSPORIN 1. Plasma concentrations of ciclosporin are t when co-administered with diltiazem, nicardipine, verapamil and possibly amlodipine and nisoldipine. However, calcium channel blockers seem to protect renal function 2. Ciclosporin t nifedipine levels 1. Uncertain presumed to be due to impaired hepatic metabolism. Also, diltiazem and verapamil inhibit intestinal P-gp, which may t the bioavailability of ciclosporin. Uncertain mechanism of renal protection 2. Uncertain effect of ciclosporin on nifedipine 1. Monitor ciclosporin levels and i dose accordingly (possibly by up to 25-50% with nicardipine) 2. Monitor BP closely and warn patients to watch for signs of nifedipine toxicity... 

Ciclosporin increases the survival of allografts in man. However, it causes renal vasoconstriction and increases proximal tubular reabsorption, leading in some cases to hjrperten-sion (20). The concomitant use of calcium channel blockers can prevent most of these adverse effects of ciclosporin. However, some calcium channel blockers (verapamil, dUtia-zem, nicardipine) can increase plasma concentrations of ciclosporin up to three-fold through inhibition of cjhochrome P450. Eight different studies have been performed on the combination of amlodipine and ciclosporin given for 1-6 months to kidney transplant recipients, and the results have been reviewed (21). In three studies, in a total of 41 patients, amlodipine increased ciclosporin concentrations, while in the others, a total of 85 patients, there was no evidence of an interaction. 

In normotensive renal transplant recipients treated for 2 months with amlodipine there was a small but significant nephroprotective effect (22). Thus, amlodipine, in contrast to other calcium channel blockers, does not affect ciclosporin blood concentrations and can be safely added in transplant recipients. 

Calcium channel blockers are given to transplant patients for their protective effect against cidosporin-induced nephrotoxicity and to optimize ciclosporin immunosuppression in order to reduce early rejection of renal grafts. Nifedipine has been used to treat cidosporin-induced hypertension, although amlodipine may be just as effective (185). 

However, some calcium channel blockers have pharmacokinetic interactions diltiazem, verapamil, nicardipine, and amlodipine increase ciclosporin concentrations, whereas nifedipine, felodipine, and isradipine do not (SED-14, 604) (SEDA-21, 210) (SEDA-21, 212)... 

Diltiazem, nicardipine and verapamil markedly raise serum ciclosporin levels but also appear to possess kidney protective effects. A single case describes elevated ciclosporin levels caused by nisoldipine. Nifedipine normally appears not to interact, but rises and falls in ciclosporin levels have been seen in a few patients. Fe-lodipine, isradipine, lacidipine and nitrendipine normally appear not to raise serum ciclosporin levels. Amlodipine has modestly increased ciclosporin levels in some studies, but not in others, and it may also have kidney-protective properties. 

Mouth Gingival enlargement is often associated with calcium channel blockers and ciclosporin. In 93 renal transplant recipients who had taken ciclosporin ( = 31), ciclosporin -b nifedipine ( = 31), or ciclosporin -b amlodipine (n = 31), more... 

Nifedipine The incidence of gingival hyperplasia has been studied in 31 patients taking ciclosporin, 31 taking ciclosporin - - amlodi-pine, and 31 taking ciclosporin - - nifedipine [23 ]. There was gingival hyperplasia in 16, 18, and 28 respectively furthermore, more of those who took ciclosporin - - nifedipine had severe hyperplasia ( = 7), compared with ciclosporin alone ( = 0) and ciclosporin + amlodipine (n = 5). 

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