Patients who receive solid organ or allogeneic hematopoietic stem cell transplants are required to take long-term immunosuppressant drugs to prevent rejection and graft-versus-host disease. The drug and dosage selection of immunosuppressants is usually individualized for the patient based on the type of transplant, target blood level, body weight, drug–drug interactions, and the risk of rejection or toxicity. The complexity of the selection process can introduce the risk for errors. Almost 20 years ago, ISMP alerted health care practitioners about Sandimmune (cyclosporine capsules and oral solution) and how this nonmodified form of the drug has decreased bioavailability compared with Neoral or Gengraf (cyclosporine [modified] capsules and oral solution). At the time, a survey by Novartis identified that 24% of prescriptions failed to specify which form of the drug should be dispensed, and only 22% of these prescriptions were clarified. We mention this because, 20 years later, we are still receiving reports of patients receiving Sandimmune when the prescriber’s preference was for a cyclosporine (modified) oral formulation. For example, three patients received Sandimmune instead of the more appropriate form of the drug, Neoral or Gengraf. In another case, during medication reconciliation, a nurse documented that a hospitalized patient was taking cyclosporine but did not verify the brand name to determine the form of the drug. The patient’s physician prescribed Sandimmune, and the patient received a dose before a pharmacy technician discovered that the patient had recently filled a prescription for Gengraf. Many transplant centers use oral solution formulations of immunosuppressant agents to allow greater flexibility in dosage adjustments, especially for pediatric patients. In one case, a 10-fold overdose of cyclosporine (modified) oral solution was administered to a child. The physician prescribed 0.5 mL (50 mg), and the pharmacy dispensed a sealed package of the medication (100 mg/mL), which contained a 5-mL oral syringe provided by the manufacturer that was calibrated in 1-mL increments, with hash marks between each milliliter. The child’s parent administered 5 mL (500 mg) instead of 0.5 mL to the child for several days. Since immunosuppressant agents have significant interpatient dosing variability, dosage delivery devices need to be selected specifically for each patient, and one size does not fit all. In this case, the 5-mL syringe size was significantly larger than each intended dose and did not facilitate accurate measurement and delivery of the prescribed dose. If the pharmacy that dispensed the cyclosporine had used a teach-back method during counseling, for instance, the dosing error might have been avoided. Cyclosporine and cyclosporine (modified) products are not interchangeable. Blood levels must be monitored to prevent serious consequences if a transplant patient receives the wrong formulation. Consider the following recommendations to reduce the risk of errors:▪Prescribers should indicate the brand name, and pharmacists should clarify prescriptions for cyclosporine.▪Order entry systems should clearly display these different forms of the drug, and a hard stop should force verification of the correct drug form during prescribing.▪Upon dispensing an oral solution, pharmacists should evaluate the appropriateness of the dosage delivery device included in the package. To improve accuracy and safety, select the dosage delivery device that will work best for the patient and his or her specific dose. A 2017 study found that providing dosing devices that closely matched the prescribed volume per dose offered the greatest reduction of errors.1.Yin H.S. et al.Pediatrics. 2017; 140 (e20163237)Google Scholar▪Health professionals, using a teach-back method, should ask patients and caregivers to show them how they will withdraw and measure oral liquid medications using their dosage delivery device.
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Mar 26, 2021
Sofia Moutinho 
Open Access