Nifedipine Ciclosporin

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... 

Gingival hyperplasia, similar to that seen with phenytoin and ciclosporin, is a rare but well-recognized adverse effect of nifedipine (88). It has also been reported in patients taking felodipine (89,90), nitrendipine (SEDA-16, 200), and verapamil (91), suggesting that this adverse effect is a class effect. Only one case of gingival hyperplasia related to calcium channel blockers was reported to the Norwegian Adverse Drug Reaction Committee up to 1991, despite their widespread use (92). However,... 

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)... 

SEDA-22,216). Two confirmations of these observations have been published. In a retrospective study of 103 transplant patients verapamil and diltiazem, but not nifedipine or isradipine, caused a significant increase in plasma ciclosporin concentrations (186). The effect of verapamil and diltiazem on ciclosporin concentrations was independent of dosage. In a crossover comparison between verapamil, felodipine, and isradipine in 22 renal transplant recipients, verapamil interacted... 

The effects of antihypertensive agents have been evaluated in patients taking ciclosporin. Collectively, dihydropyridine calcium channel blockers that do not affect ciclosporin blood concentrations substantially or at all (felodipine, isradipine, and nifedipine) are usually considered to be the drugs of choice. However, the risk of gingival hyperplasia with nifedipine, which ciclosporin also causes, should be borne in mind. Combination therapy with angiotensin-converting enzyme inhibitors or beta-blockers, or the use of other calcium channel blockers (verapamil or diltiazem) should also be considered, but careful monitoring of ciclosporin blood concentrations is recommended with the latter because they inhibit ciclosporin metabolism. 

The combination of ciclosporin with nifedipine produces an additive on gingival hyperplasia, with an increased prevalence and/or severity (SED-13, 1127) in both children (77,81) and adults (76,80,82). In contrast, verapamil had no significant additional effects on the prevalence or severity of ciclosporin-induced gingival overgrowth (SEDA-21, 385). 

Nifedipine and ciclosporin can cause gingival hyperplasia, which is associated with gingival inflammation and can be mitigated by careful oral hygiene, although this has not been clearly shown. In gingival biopsies from nine... 

In another study, gingival samples were collected from 19 healthy individuals, 12 nifedipine-treated cardiac patients, and 22 immunosuppressant-treated organ transplant recipients, 11 of whom were also taking nifedipine (23). Mitotic activity was measured in the basal cell layer, and the results suggested that the increased epithelial thickness observed in nifedipine- and ciclosporin-induced gingival overgrowth is associated with increased mitotic activity. 

Ciclosporin significantly inhibits the metabolism of nifedipine, leading to increased effects (53). 

Imatinib increases serum tacrolimus levels and is therefore predicted to increase ciclosporin levels. Imatinib may also increases the levels of some benzodiazepines (e.g. midazolam), some calcium-channel blockers (e.g. nifedipine), oestrogens, paracetamol, pimozide, and warfarin. In one case lansoprazole was suspected to have raised imatinib levels. 

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. 

The situation with nifedipine is not totally clear (no effect or decreases or increases) but it appears to have a kidney-protective effect as does fe-lodipine. The manufacturers of ciclosporin recommend avoiding nifedipine in patients who develop gingival overgrowth. ... 

A man with a kidney transplant taking corticosteroids and ciclosporin developed a cytomegalovirus infection that was treated with foscarnet 85 mg/kg daily. Despite efforts to minimise the nephrotoxic effects of the foscarnet (hydration with 2.5 litres of isotonic saline daily and nifedipine 80 mg the day before and during treatment) the patient developed non-ol-iguric worsening of his renal function after 8 days. Nine days after stopping the foscamet, the former renal function was restored. ... 

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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