Issue 7 July 2001
Update on Prograf®'s Assistance Program	New Medications Prozac Weekly® (Fluoxetine), Valcyte™ (valganclovir HCL), Nexium® (esomeprazole)	MAP Status Report October 1, 1999 - June 30, 2001

Update on Prograf®'s Assistance Program According to Fujisawa/Covance, patients who are currently enrolled in their patient assistance program for the drug Prograf® and who are believed to be Medicare eligible will no longer qualify to receive this medication free from the manufacturer. Fujisawa/Covance, who administers the program, has contacted patients enrolled in the program to assess their Medicare eligibility. It is important to note that those patients who are terminated by Fujisawa/Covance under the assistance program will be responsible for purchasing their Prograf®, which typically ranges between $600-$1200 per month, or finding assistance to help pay for the medication. Fortunately, to date, this is not the practice of the other immunosuppressive companies such as Abbott (Gengraf®), Novartis (Neoral® and Sandimmune®), Roche (CellCept®) and Wyeth (Rapamune®).

New Medications Prozac Weekly® (Fluoxetine) The FDA has approved Prozac Weekly®, a new formulation of fluoxetine developed by Eli Lilly and Company, for weekly administration to patients suffering from depression who are stabilized on daily fluoxetine. It is the only prescription medication administered weekly that is currently available for long-term treatment of depression. Prozac Weekly® contains 90 mg of fluoxetine pellets with an enteric coating that delays its release by 1 to 2 hours. Weekly use of fluoxetine has been shown to cause more fluctuations in serum concentrations and steady-state concentrations that are about 50% lower than daily use fluoxetine. In a 25-week double-blind trial in 501 patients with major depression who responded to daily fluoxetine, relapse rates were 26% with daily fluoxetine, 37% with weekly fluoxetine, and 50% with placebo. Although adverse effects were similar, diarrhea and cognitive problems were more common in patients who received weekly fluoxetine. Other studies suggest that three 20 mg capsules of fluoxetine once weekly may also be effective. More studies are needed to determine whether once-weekly fluoxetine is as effective and safe as taking smaller doses of the drug once daily. It is recommended that patients wait one week after they stop taking daily fluoxetine before beginning Prozac Weekly®. The 90 mg weekly dose does not work for everyone and some patients may do better with daily dosing. For patients who may benefit from Prozac® but may not have the resources to purchase the product, a patient assistance program is available. To access the program, call MAP or Lilly Cares at 800-545-6962. Authored by Hollie Hightower Valcyte™ (Valganclovir HCL) Valcyte™ (valganclovir HCL), indicated for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS, is a valine ester prodrug of ganciclovir and is extensively hydrolyzed to ganciclovir following oral administration. In a clinical trial of 160 patients with AIDS, oral valganclovir provided a convenient and effective alternate to IV ganciclovir for treating CMV retinitis. Studies have also been conducted in CMV retinitis transplant patients. In a pharmacokinetic study of liver transplant patients, 450 mg of oral valganclovir delivered systemic ganciclovir exposure comparable to oral ganciclovir 1000 mg TID, and 900 mg of oral valganciclovir provided exposure comparable to 5 mg/kg IV ganciclovir. The recommended dose of Valcyte™ is 900 mg BID for 21 days for active CMV retinitis and 900 mg once daily for maintenance. The adverse events reported were similar in frequency and severity to those associated with ganciclovir and included headache, nausea, and diarrhea. Valcyte™ must be adjusted for renal impairment. For patients who may benefit from Valcyte™ but may not have the resources to purchase the product, a patient assistance program is available. To access the program, call MAP or Roche at 1-800-282-7780. Nexium® (Esomeprazole) Nexium® (esomeprazole), the S-isomer of Prilosec® (omeprazole), was approved by the FDA in February 2001. It is metabolized slower, has higher and more prolonged drug concentrations and longer acid suppression than Prilosec®, which is a mixture of S- and R-isomers. Nexium® is indicated for GERD (gastroesophageal reflux disease), erosive esophagitis, and for combination use with amoxicillin and clarithromycin to treat H. pylori. In a controlled trial involving 1960 patients, Nexium® was shown to be more effective than Prilosec®. The study compared the healing rates of erosive esophagitis in patients who received esomeprazole 40 mg, esomeprazole 20 mg, and omeprazole 20 mg daily. The researchers found that after 8 weeks of treatment, esomeprazole 20 mg and 40 mg produced 90% and 94% healing rates, respectively, while omeprazole produced 87%. This study also found that esomeprazole produced a more rapid onset of sustained relief. Nexium® is available in 20 and 40mg capsules. As with other proton pump inhibitors, headache, diarrhea, nausea, flatulence, abdominal pain, constipation and dry mouth have been reported. Similar to other medications that suppress gastric acid, Nexium® may interfere with the bioavailability of drugs dependent on acidic pH for absorption (e.g., ketoconazole, digoxin). AstraZeneca has priced the standard dose of Nexium® (20 to 40 mg daily) slightly less than Prilosec® in an attempt to make it more appealing to patients and physicians. The biggest challenge that Nexium® faces is whether or not the therapeutic improvements and pricing strategy will be enough to overcome the cost savings of generic omeprazole which is expected to be out this fall. A patient assistance program is available for Nexium®. To access the program, call MAP or AstraZeneca at 1-800-424-3727. Authored by Dr. James Oester

MAP Status Report From October 1, 1999 to June 30, 2001, MAP has aided over 200 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 $1.6 million in medications (based on average wholesale prices). Approximately 50% of these medications represent immunosuppressants and the remaining represent cardiovascular, antimicrobial, gastrointestinal, and other necessary prescription medications. MAP also serves as a valuable resource to healthcare professionals and transplant patients by providing the most up-to-date information concerning medication assistance programs. MAP is made available by the 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 800-736-2273 EXT. 0131.

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.