Issue 1 January 2000
Reimbursement Programs Medication Access Program	Recent FDA Approvals Rapamune® and Aciphex®	Medication Safety Rhabdomyolysis®

Reimbursement Programs The Medication Access Program (MAP) is a new statewide program for solid organ transplant patients in Georgia that offers information about pharmaceutical manufacturer-sponsored medication assistance programs. The mission of MAP is to increase access to medications for solid organ transplant patients who reside in the state of Georgia. MAP is available through a grant from the Carlos and Marguerite Mason Trust and the University of Georgia College of Pharmacy. Financial circumstances resulting from a lack of medication coverage may force transplant patients to become noncompliant with medications. Noncompliance with immunosuppressants and other critical transplant medications may lead to organ rejection, increased health care cost and decreased quality of life. MAP will aid transplant patients in the enrollment process required to participate in medication assistance programs. If the patient meets selection criteria for the specific program, MAP personnel will assist the patient in the actual enrollment process. Additionally, MAP will be a valuable resource to health care professionals and transplant patients by providing the most up-to-date information regarding available reimbursement assistance programs. MAP will provide information about reimbursement assistance programs that provide immunosuppressant medications and medications for concomitant disease states that may develop in transplant patients. These disease states include, but are not limited to, hypertension, diabetes, chronic obstructive pulmonary disease and lipid disorders. We encourage all transplant patients and health care professionals to contact MAP. MAP personnel may be reached Monday through Friday from 9am to 5pm by calling 706-721-0131 or 800-736-2273 extension 0131.

Recent FDA Approvals Rapamune® (sirolimus) The FDA has recently approved a new immunosuppressant medication, Rapamune® (sirolimus), to prevent acute organ rejection in patients receiving kidney transplants. It is manufactured by Wyeth Ayerst Laboratories. Sirolimus acts by a mechanism similar to other immunosuppressants, and has few overlapping toxicities with existing therapies. The safety and efficacy of sirolimus is supported by two randomized, double-blind, multicenter controlled trials (data on file with Wyeth-Ayerst Laboratories). These studies compared two dose levels of sirolimus oral solution (2 mg and 5 mg once daily) with azathioprine or placebo when administered in combination with cyclosporine and corticosteroids. These studies showed that, compared to regimens including cyclosporine and corticosteroids in combination with azathioprine, sirolimus combinations were as effective as cyclosporine combinations in reducing rejection rates in the incidence of all grades of acute rejection episodes. Adverse events associated with its use include an increase in serum cholesterol and triglycerides. It is recommended that sirolimus be separated by four hours from any oral dose of cyclosporine. It should be taken in a consistent manner with or without food, and is administered as a liquid mixed with water or orange juice. Grapefruit juice should not be consumed with sirolimus or used for dilution. Aciphex® (rabeprazole) Aciphex® (rabeprazole) is a new proton pump inhibitor developed by Eisai Incorporated and marketed in the United States in a combined effort between Eisai Incorporated and Janssen Pharmaceuticals. It is indicated in the short-term (4 to 8 weeks) treatment for healing of erosive or ulcerative gastroesophageal reflux disease (GERD), for maintaining healing of erosive or ulcerative GERD, short-term (up to four weeks) treatment in the healing of duodenal ulcers, and treatment of pathological hypersecretory conditions. In clinical trials rabeprazole was found to be as effective as omeprazole in the treatment of erosive or ulcerative GERD and duodenal ulcers. The tolerability of rabeprazole in clinical trials was similar to that of famotidine, ranitidine and omeprazole. Commonly reported adverse events include malaise, nausea, diarrhea, headache, dizziness and skin eruptions. The recommended adult oral dose of rabeprazole is 20 mg once daily. There is no dosage adjustment necessary in elderly patients, but there is a lack of clinical data on its use in patients with hepatic impairment. Caution should be exercised in these patients.

Medication Safety Rhabdomyolysis® Cardiovascular disease as a result of hyperlipidemia occurs in greater than 50% of transplant patients, and is associated with high morbidity and mortality. The 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (eg, Pravachol®, Lescol®, Mevacor®, Zocor®, Lipitor®) are commonly used for treatment of posttransplant hyperlipidemia due to other agents either being contraindicated or having adverse effects that are not well tolerated in this population. The concern of development of myopathy or rhabdomyolysis, defined as an increase in creatine kinase levels more than ten times the upper limit of normal, is a concern for transplant patients taking cyclosporine and HMG-CoA reductase inhibitors. All of the reductase inhibitors have been associated with the development of rhabdomyolysis/myopathy in clinical trials and cited in case reports. Toxicity usually depends on the dose of the HMG-CoA reductase inhibitor. In this population it remains efficacious to initiate therapy at a lower dose. In many cases this adverse event may be asymptomatic, and close surveillance of creatine kinase levels is warranted in patients receiving the combination of cyclosporine with an HMG-CoA reductase inhibitor. Other signs and symptoms to look for include muscle weakness and red tinted urine secondary to myoglobin in the urine.

The MAP newsletter is published quarterly to present topics of interest to the transplant community. If you would like to submit material to be considered for publication in the newsletter, please contact MAP at: Medication Access Program University of Georgia at the Medical College of Georgia Clinical Pharmacy Program CJ-1020 Augusta, Georgia 30912-2450 (706) 721-0131 or 1-800-736-2273 ext. 0131 E-mail - map@mapuga.com

The Medication Access Program is a statewide program for solid-organ transplant patients in Georgia that offers information about medication assistance programs and helps with the enrollment into these programs.