Before the early 1980s, patient and allograft survival for solid organ transplant recipients was dismal. By 1983, the first calcineurin blocker, cyclosporine (Sandimmun), had been introduced, and outcomes were dramatically improved. However, cyclosporine macroemulsion had suboptimal pharmacokinetics, significant drug interactions, and several adverse effects, including nephrotoxicity, neurotoxicity, hyperlipidemia, and hypertension. Recent advances with cyclosporine include the introduction of modified dosage formulations: Neoral, a microemulsion, and several generic microemulsion products. The potent second-generation calcineurin blocker tacrolimus (Prograf) was introduced in 1994 and has become the drug of choice for several types of transplant recipients. Although tacrolimus has improved pharmacokinetics and therapeutic drugmonitoring parameters, it has adverse effects such as nephrotoxicity, neurotoxicity, and diabetes. Thus, current immunosuppressive regimens implementing calcineurin blockers often involve additional immunosuppressive agents to “spare” the use of these agents, minimizing their adverse effects. This article reviews the mechanisms of action, pharmacokinetics, clinical use, therapeutic drug monitoring, drug interactions, adverse effects, and dosing of cyclosporine and tacrolimus in solid organ transplant recipients.
Aneurysms in abdominal organ transplant recipients
