Recommendations for Use of Certican ® (Everolimus) After Heart Transplantation: Results From a German and Austrian Consensus Conference

Abstract

The Certican Consensus Conference has produced guidelines to help physicians apply Certican (everolimus) clinical trial data in clinical practice. Everolimus is indicated in combination with cyclosporine microemulsion (CsA; Neoral) and corticosteroids for prophylaxis of acute rejection after heart transplantation. It has also shown efficacy for prevention of cardiac allograft vasculopathy. Further indications for use pertain to patients with chronic renal failure, to allow reduced calcineurin inhibitor (CNI) exposure; reduce the risk of cytomegalovirus to disease; second transplantation; heart/lung transplantation after occurrence of bronchiolitis obliterans; and in patients with malignancies under immunosuppression. Contraindications include intolerance, severe leukocytopenia and severe thrombocytopenia. The everolimus dose is 0.75 or 1.5 mg twice daily, adjusted according to trough blood levels. Target blood levels are 3 to 8 ng/ml, with 6 to 8 ng/ml considered the optimal range for most patients. Recommended CsA trough blood levels in patients receiving everolimus are 150 to 175 ng/ml for Months 1 to 3 post-transplant, around 135 ng/ml for Months 3 to 6, and <100 ng/ml after Month 6. It may be possible to discontinue steroids in patients receiving long-term everolimus and CsA. Early cytomegalovirus prophylaxis is recommended for patients with a high-risk mismatch, and trimethoprim-sulfamethoxazole should be given to prevent Pneumocystis carinii. Everolimus dose should be reduced by about 50% if administered in conjunction with azoles or erythromycin, and increased 100% to 200% if given with rifampicin. All heart transplant recipients should receive statins unless contraindicated.