Issue 5 January 2001
MAP Status Report MAP Helps Transplant Patients Receive over $1 Million in Medications	Updates on Patient Assistance Programs Rapamune®, Protonix®, Glucovance®, Imuran®, Zyloprim® and Actigal®	Recent FDA Approval Glucovance™	St. John's Wart Implicated in Kidney Transplant Rejection

MAP Status Report MAP Helps Transplant Patients Receive over $1 Million in Medications The mission of the Medication Access Program (MAP) is to increase access to medications for solid-organ transplant patients who reside in the state of Georgia. From October 1999 through December 2000, MAP has aided over 170 Georgia solid-organ transplant patients in the enrollment process required to participate in medication assistance programs. Through MAP's services, these patients have received over $1 million of medications, based on average wholesale prices. These medications mostly represent immunosuppressants, cardiovascular, antimicrobial, gastrointestinal, and other necessary prescription medications. MAP also serves as a valuable resource to health care professionals and transplant patients by providing the most up-to-date information concerning medication assistance programs. MAP is made available by the Carlos and Marguerite Mason Trust and the University of Georgia College of Pharmacy. For more information, MAP personnel may be reached Monday through Friday from 9am to 5pm by calling 706-721-0131 or 1-800-736-2273 EXT. 0131.

Updates on Patient Assistance Programs Several new patient assistance programs are available. Rapamune® (sirolimus), manufactured by Wyeth-Ayerst Laboratories, is an immunosuppressant used to prevent acute organ rejection in patients receiving kidney transplants. For patients that may benefit from Rapamune® but may not have the resources to purchase this medication, information concerning patient assistance may be accessed through MAP at 706-721-0131 or directly through RapAssist at 1-877-472-7268. Protonix® (pantoprazole sodium), a medication that suppresses the final step in gastric acid production, has a medication assistance program for those patients who qualify. For more information concerning this program, contact MAP at 706-721-0131 or Wyeth-Ayerst Laboratories at 1-800-568-9938. Glucovance also has a patient assistance program (see article below). Enrollment for patient assistance with lmuran® Zyloprim®, and Actigal® is no longer available.

Recent FDA Approval Glucovance™ The U.S. FDA has approved Glucovance™ (a combination of glyburide and metformin) for use, along with diet and exercise, as initial and second-line drug therapy for people with type 2 diabetes. Glucovance™ is available in three strengths, including 1.25 mg/250 mg (glyburide/metformin) tablets, 2.5 mg/500 mg tablets, and 5 mg/500 mg tablets and should be given with meals to avoid hypoglycemia. Because it is a combination product, the same precautions and side effects that apply to each agent individually apply to the combination. The most common side effects include diarrhea, nausea, upset stomach, and symptoms of hypoglycemia (lightheadedness, dizziness, shakiness, or hunger). The most serious side effect that Glucovance™ can cause is lactic acidosis. Lactic acidosis with Glucovance™ is rare and has occurred mostly in people whose kidneys were not working normally. Lactic acidosis has been reported in about one in 33,000 patients taking metformin over the course of a year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the cases. Contraindications for use of Glucovance™ include: renal disease or dysfunction (suggested by SCr levels greater than or equal to 1.5 mg/dL in males and greater than or equal to 1.4 mg/dL in females); congestive heart failure requiring pharmacologic treatment; known hypersensitivity to metformin or glyburide; and acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Glucovance™ should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. For patients who may benefit from Glucovance™ but may not have the resources to purchase the product, Bristol-Myers Squibb Company has a patient assistance program available which may be accessed through the MAP program or directly through the company at 1-800-736-0003.

St. John's Wort Implicated in Kidney Transplant Rejection St. John's Wort is a common perennial herb that grows wild in much of the world and is most commonly used to treat mild to moderate depression. Reports in the medical literature show that regular use of St. John's Wort can elevate the activity of multiple liver cytochromes as well as the transport protein P-glycoprotein, causing great potential for drug interactions. In October 2000, at the annual meeting of the American Society of Nephrology, two case reports were presented implicating St. John's Wort in kidney transplant rejection because of it's potential for interference with cyclosporine metabolism. The first case was that of a 44-year old woman who underwent living-related kidney transplant in February 1996. She began experiencing acute rejection in the Fall of 1999 and was referred to a specialty clinic in December 1999. The patient had been receiving maintenance doses of cyclosporine, but recently had been prescribed higher doses because of a sudden drop in blood levels. Even with the increased dose, the levels of cyclosporine in the blood remained low for 6 months. Her physicians discovered that the patient had been taking St. John's Wort daily at the same time that she took her cyclosporine. She stopped taking the herb and within 2 weeks her cyclosporine trough levels had returned to a normal range. After 4 weeks, physicians were able to reduce her cyclosporine dose, and the blood levels remained in the therapeutic range. The second case was a 29-year old woman who had undergone combined cadaveric kidney and pancreas transplant in July 1994. The patient had two early episodes of rejection which clinicians were able to stabilize. Her cyclosporine trough levels stayed in the therapeutic range until November 1998. Over the course of several days, her cyclosporine levels dropped significantly and serum creatinine increased even though she remained on the same dose. Her physicians found that this patient was taking St. John's Wort. When she discontinued use of the herb and her dosage of cyclosporine was increased, her levels increased to 530 ng/mL. The dose was adjusted again and levels dropped to a normal range. Unfortunately, the patient eventually developed acute rejection and underwent another renal transplant in January 2000.

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.