Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Current strategies and future trends in immunosuppression after heart transplantation.

PURPOSE OF REVIEW: Current immunosuppressive drugs have provided excellent outcomes after heart transplantation. However, more patients suffer from long-term complications of these drugs. A series of prospective randomized trials has been conducted and has offered disparate results. This report reviews the challenges of immunosuppressive therapy during the past decade, describes recent reports and explores potential future trends in immunosuppressive protocols in heart transplantation. RECENT FINDINGS: The traditional combination of cyclosporine, azathioprine and steroids has been changed to tacrolimus (Tac) or cyclosporine in combination with mycophenolate mofetil (MMF) and steroids due to the results of several trials. The use of mammalian target of rapamycin inhibitors in combination with Tac or cyclosporine A has not shown a clear benefit compared with MMF. All different combinations have shown some positive effects counteracted by side-effects and negative synergism of combinations. Future protocols need to be adapted according to individual patient's needs and risks. SUMMARY: The changing population of heart transplantation patients has become older and sicker. Immunosuppression strategies should be developed for each patient based on their risk for rejection and their risk for developing important complications of immunosuppressive therapy.

Increased rejection rates in cardiac transplant associated with dexamethasone.

BACKGROUND: Peri-operative immunosuppression in cardiac transplantation includes the use of intravenous methylprednisolone. During a national shortage, intravenous dexamethasone was substituted for methylprednisolone at standard equivalencies. Methylprednisolone and dexamethasone are used interchangeably in many clinical settings; however, their equivalency has not been demonstrated. METHODS: Forty-two consecutive cardiac transplant patients were studied retrospectively. All patients received standard triple immunosuppression. Eighteen patients received dexamethasone and 24 methylprednisolone. Twelve patients were included for comparison after the methylprednisolone shortage resolved. Endomyocardial biopsy (EMB) results graded as > or =1B (ISHLT classification) were considered positive for acute cellular rejection. RESULTS: More patients who received dexamethasone as induction had cellular rejection (12/17; (70%) vs. 14/33; (42%); p=0.05). Four patients were excluded because of deaths unrelated to cardiac function. The increased rate of rejection seen during dexamethasone substitution declined after reinstitution of methylprednisolone (p=0.05). CONCLUSIONS: Peri-operative high-dose dexamethasone in cardiac transplants was associated with higher rates of acute cellular rejection. The equivalencies of dexamethasone and methylprednisolone differ from accepted standards when used in pulse doses. Peri-operative use of glucocorticoids may rely on mechanisms that are different from those considered in the standard equivalency measures. Pulse doses of dexamethasone and methylprednisolone in transplantation may not be interchangeable at standard equivalencies.

Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant recipients.

PURPOSE: The implications of the findings from clinical studies and pharmacokinetic analyses of the antiviral agent valganciclovir for dosing of the drug to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are reviewed. SUMMARY: Valganciclovir, an oral prodrug of ganciclovir, is as effective as oral ganciclovir for preventing CMV disease, although prophylaxis with either agent may delay CMV disease. Dosage reduction is required for both drugs in patients with renal impairment to prevent high plasma ganciclovir concentrations and toxicity. A valganciclovir dosage of 900 mg/day is required in patients with normal renal function, especially those at high risk for CMV disease, to provide adequate systemic ganciclovir exposure. Some studies suggest that a lower dosage might suffice for patients at a low risk for CMV disease. CONCLUSION: Valganciclovir dosing should be based on renal function to avoid toxicity.