Ciclosporin interactions

The ciclosporin interaction may be partly due to the vehicle used in intravenous preparations. One idea is that Cremophor, a surfactant which has been used as a solvent for the ciclosporin, may increase the effective concentration of pancuronium at the neuromuscular junction. Both compounds have been observed in animal studies to increase vecuronium blockade, and Cremophor has also been seen to decrease the onset time... 

Direct information seems to be limited to the reports cited, and the interactions are not established. Although retrospective data suggest that aza-thioprine and antilymphocyte immunoglobulins can cause a reduction in the effects of neuromuscular blockers, and in some cases the dosage may need to be increased two- to fourfold, the only prospective study found that the interaction with azathioprine was not clinically significant. The general importance of the ciclosporin interaction is also uncertain, but be alert for an increase in the effects of atracurium, pancuronium or vecuronium in any patient receiving ciclosporin. Not all patients appear to develop this interaction. More study is needed. 

Interactions Antacids ciclosporin colestipol druas metabolized bv cytochrome P450 3A4 fibrates oral-contraceptiyes warfarin niacin erythromycin diaoxin azole-antifunaals... 

Q35 Cli nically significant drug interactions with ciclosporin could occur... 

There is an increased risk of hyperkalaemia when ciclosporin is given with Coversyl, which contains perindopril, an angiotensin-converting enzyme inhibitor. Risk of nephrotoxicity associated with ciclosporin is increased with concomitant use with quinolones. Ciproxin contains ciprofloxacin, which is a quinolone. Tenormin contains atenolol, which is a beta-adrenoceptor blocker and there are no interactions between these agents and 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. 

Several case reports have suggested that the elimination of ciclosporin can be impaired by oral contraceptives, resulting in increased plasma ciclosporin concentrations. Ciclosporin undergoes hydroxylation and /V-dcmethyla-tion, in which cytochrome P450 is involved, so competitive enzyme inhibition probably explains the interaction. Dosages of ciclosporin should be reviewed carefully (340). 

Rosiglitazone is not metabolized by CYP3A4 and interactions with drugs such as ciclosporin and tacrolimus are therefore not expected. Several studies have confirmed this. 

Most drug interactions associated with rhabdomyolysis occur when ciclosporin is combined with simvastatin or lovastatin. It has been suggested that if a statin is to be combined with ciclosporin, pravastatin or fluvastatin should be chosen instead (80). 

Rhabdomyolysis in a stable renal transplant recipient was attributed to the presence of red yeast rice (Monascus purpureus) in a herbal mixture (116). The condition resolved when he stopped taking the product. Rice fermented with red yeast contains several types of mevinic acids, including monacolin-K, which is identical to lovas-tatin. The authors postulated that the interaction of ciclosporin with these compounds through cytochrome P450 had resulted in the adverse effect. Transplant recipients must be cautioned against using herbal products to lower their lipid concentrations, in order to prevent such complications. 

Lampen A, Christians U, Bader A, et al. Drug interactions and interindividual variability of ciclosporin metabolism in the small intestine. Pharmacology 1996 52 (3) 159-168. 

Let doctors, dentists, nurses and pharmacists know that you are taking this medicine. It may affect their choice of treatment. Note that ibuprofen is a general sale list medicine and so can be freely purchased. This can interact with ciclosporin and so should generally be avoided without further medical advice. 

VASODILATOR ANTIHYPERTENSIVES CICLOSPORIN 1. Co-administration of bosentan and cidosporin leads to t bosentan and 1 cidosporin levels 2. Risk of hypertrichosis when minoxidil given with cidosporin 3. t sitaxentan levels 1. Additive effect both drugs inhibit the bile sodium export pump, which is associated with hepatotoxicity 2. Additive effect 3. Uncertain 1. Avoid co-administration of bosentan and cidosporin 2. Warn patients of the potential interaction 3. Avoid co-administration... 

ACEBUTOLOL, ATENOLOL, BETAXOLOL, BISOPROLOL, METOPROLOL, PROPANOLOL CICLOSPORIN t risk of hyperkalaemia Beta-blockers cause an efflux of potassium from cells, and side-effect has been observed during cidosporin therapy Monitor serum potassium levels during co-administration > For signs and symptoms of hyperkalaemia, see Clinical Features of Some Adverse Drug Interactions, Hyperkalaemia... 

POTASSIUM-SPARING DIURETICS CICLOSPORIN t risk of hyperkalaemia Additive effect >- For signs and symptoms of hyperkalaemia, see Clinical Features of Some Adverse Drug Interactions, Hyperkalaemia... 

STATINS- ATORVASTATIN, LOVASTATIN, ROSUVASTATIN, SIMVASTATIN CICLOSPORIN t plasma concentrations of these statins, with risk of myopathy and rhabdomyolysis Cidosporin is a moderate inhibitor of CYP3A4, which metabolizes these statins 1 statins to lowest possible dose (do not give simvastatin in doses >10 mg). Monitor LFTs and CK closely warn patients to report any features of rhabdomyolysis. This interaction does not occur with pravastatin... 

Therapeutic drug monitoring is essential with ciclosporin therapy with or without the concurrent administration of drugs with the potential to cause interactions. 

CICLOSPORIN CIPROFLOXACIN Ciprofloxacin may 1 immunosuppressive effect (pharmacodynamic interaction) Ciprofloxacin 1 inhibitory effect of ciclosporin on IL-2 production to 1 immunosuppressive effect Avoid co-administration... 

CICLOSPORIN DOXORUBICIN High doses of cidosporin T AUC of doxorubicin by 48% and of a metabolite by 443%. Risk of severe myelosuppression and neurotoxicity Cidosporin inhibits P-gp and cytochrome P450, which results in 1 clearance of doxorubicin Advise patients to report symptoms such as sore throat, fever, bleeding and bruising - For signs and symptoms of immunosuppression, see Clinical Features of Some Adverse Drug Interactions, Immunosuppression and blood dyscrasias... 

CICLOSPORIN BZDs-ALPRAZOLAM, MIDAZOLAM, DIAZEPAM Likely t plasma concentrations and risk of t sedation These BZDs are metabolized primarily by CYP3A4, which is moderately inhibited by cidosporin Warn patients about t sedation. Consider using alternative drugs, e.g. flurazepam, quazepam. Warn about activities requiring attention - For signs and symptoms of CNS depression, see Clinical Features of Some Adverse Drug Interactions, Central nervous system depression... 

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