Immunosuppression treatment following heart transplantation
Authors:
L. Špinarová; J. Vítovec
Authors‘ workplace:
I. interní kardioangiologická klinika, LF MU Brno
Published in:
Kardiol Rev Int Med 2009, 11(2): 63-65
Overview
In recent years, heart transplantation is the treatment of choice in patients with severe heart failure. Immunosuppressants form the basis of pharmacotherapy in these patients. The traditional immunosuppressants are cyclosporin, azathioprine and glucocorticoids. Newer treatment schedules include cyclosporin, mycophenolate mofetil and glucocorticoids or tacrolimus, mycophenolate mofetil and glucocorticoids. Recently, combinations without nephrotoxic calcineurin inhibitors (cyclosporin or tacrolimus) are preferred in post‑orthotopic heart transplantation (OHT) patients with renal function impairment. Sirolimus or everolimus are used instead in combination with mycophenolate. We aim to cease glucocorticoids in all treatment regimens after the first year of treatment with the resulting two‑drug combination being life-long. Drug interactions are the most frequently linked to cyclosporin. The drugs that increase cyclosporin levels include amiodarone, cimetidine, steroids, diltiazem, erythromycin nicardipine, oral contraception, ranitidine and verapamil. The increased cyclosporin levels might lead to nephrotoxicity. On the other hand, the drugs that decrease cyclosporin levels might cause rejection (e. g. carbamazepine, antituberculotics, cholestyramine, phenobarbital). Concomitant administration of azathioprine and allopurinol might cause bone marrow suppression. Steroids enhance the effect of cyclosporin, their combination with diuretics leads to potassium depletion and ulcerogenic effect is potentiated when combined with anti‑inflammatory agents. It is well known that both cyclosporin and tacrolimus are metabolised via the CYP 450 3A4 as are atorvastatin, lovastatin, simvastatin or the newer rosuvastatin. Consequently, an interaction between these drugs may lead to increased plasmatic concentrations of the statins and increased risk of myopathies. On the other hand, since pravastatin is not metabolised via the CYP 450 system and fluvastatin metabolises via the CYP 2C9, these agents appear to be suitable pharmacological options in the post‑OHT patients as the risk of drug interactions at the CYP 450 3A4 is minimal. In the post‑OHT patients, treatment with a low dose of any statin (atorvastatin 10 mg, lovastatin 20 mg, simvastatin 10 mg, rosuvastatin 10 mg, pravastatin 20–40 mg or fluvastatin 40 mg) should be started as soon as possible following OHT. If increased cholesterol needs further control, hydrophilic fluvastatin in retarded formulation or, alternatively, pravastatin 80 mg should be selected as they are, due to their pharmacological profile, less likely to cause myopathies. In conclusion, it is imperative that cardiologists regularly monitor their patients and consult transplantation centres if in any doubt.
Keywords:
transplantation – immunosuppression – interaction
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Paediatric cardiology Internal medicine Cardiac surgery CardiologyArticle was published in
Cardiology Review
2009 Issue 2
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