Issue 2 April 2000
Clinical Issues ACE Inhibitors & ATIIRA Use in Renal Transplant Recipients	Recent FDA Approvals Aggrenox®, Avelox®, Sporanox® IV	Medication Withdrawal Propulsid®	Transplant Meeting 2000 May 13-17, 2000 in Chicago, Illinois

Clinical Issues ACE Inhibitors & ATIIRA Use in Renal Transplant Recipients A retrospective cohort analysis published in the January 2000 issue of the American Journal of Kidney Diseases (2000;35:58-63) found ACE inhibitors (ACEI) and Angiotensin II Receptor Antagonists (ATIIRA) to be useful for treatment of hypertension in renal transplant recipients. The study examined the effect of ACEI and ATIIRA on blood pressure, renal function, serum potassium and hemoglobin in renal transplant recipients. Patients were included in the study if they had been prescribed an ACEI (i.e., Lotensin®, Prinivil®, Zestril®, Vasotec®, Monopril®) or an ATIIRA (Losartan® being the only one used), and were followed-up in the clinic for a minimum of six months. All patients included in the study were screened for renal artery stenosis prior to initiating therapy with either of these classes of agents. Data was collected 3 months prior to drug initiation, at drug initiation, and at 3, 6, 12, and 36 months. The study examined 642 patient charts, and of these, 177 patients were prescribed an ACEI or ATIIRA. Of the 177 patients included, 47 patients had therapy discontinued due to adverse events. The most common reasons for discontinuation included cough and hyperkalemia. The study found that the mean arterial pressure at each follow-up period was lower than the mean arterial pressure at initiation of therapy, with a decrease from 92± 12mm Hg to 86± 9mm Hg (p< 0.05) at three years. The serum creatinine and hemoglobin for the cohort remained unchanged through the follow-up period. There was a non-sustained increase in serum potassium from 4.4± 0.5 mEq/L to 4.6± 0.6 mEq/L at three months (p< 0.05), but there were no further increases in the potassium beyond this time. The study concluded that ACEI and ATIIRA were effective, safe and well-tolerated agents for treatment of hypertension in renal transplant recipients, but further study would be beneficial in the form of a randomized clinical trial. back to top

Recent FDA Approvals Aggrenox® (dipyridamole/ASA) Aggrenox® (200 mg extended-release dipyridamole/25 mg aspirin), a new antithrombotic by Boehringer Ingelheim Pharmaceuticals, is indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or complete ischemic stroke due to thrombosis. The efficacy of Aggrenox® was established in the European Stroke Prevention Study 2 (J Neur Sci 1996; 143:1-13), which concluded that stroke risk in comparison to placebo was reduced by 18% with aspirin alone (50 mg/day), 16% with dipyridamole alone (400 mg/day) and 37% with Aggrenox® . Comparisons of Aggrenox® versus each agent alone yielded a significant 23% reduction in stroke risk over aspirin alone, and 25% reduction over dipyridamole alone. The reported adverse events during Aggrenox® therapy were similar to those reported with its components, aspirin and dipyridamole. Patients treated with Aggrenox reported a higher overall incidence of gastrointestinal disturbances, in particular diarrhea, compared with placebo. The reported incidence of bleeding was highest in those therapies containing aspirin (Drugs 1999;58:469-475). The recommended dosage is one capsule twice daily. It is supplied as a capsule containing 200 mg of dipyridamole in an extended-release form and 25 mg of aspirin in an immediate-release sugar-coated tablet. Avelox® (moxifloxacin) Avelox® (moxifloxacin), a new oral fluoroquinolone antibiotic by Bayer Pharmaceuticals, is indicated in the treatment of acute bacterial exacerbation of chronic bronchitis, community acquired pneumonia, and acute bacterial sinusitis. The drug is rapidly absorbed, with peak plasma concentrations reached within one to four hours, and the long half-life of approximately 11 to 16 hours makes it suitable for once-daily administration. The drug accumulates in lung epithelial lining fluid, bronchial mucosa and alveolar macrophages at concentrations higher than the MIC90 for most common respiratory pathogens (S. pneumoniae, H. influenzae, M. catarrhalis, K. pneumoniae). There are no significant drug or food interactions with moxifloxacin. The bioavailability is reduced with co-administration of an antacid or iron preparation, but is not affected if taken at least four hours before or eight hours after these agents. In comparison with other fluoroquinolones, moxifloxacin appears to have a low propensity for causing phototoxic and CNS excitatory effects. The most common adverse event reported in clinical trials was gastrointestinal disturbances. Moxifloxacin is supplied as a 400 mg tablet. The usual recommended dose is 400 mg once daily. There is currently no recommendation for dosage adjustment in renal impairment, but the dosage should be adjusted for hepatic impairment. Sporanox® IV (itraconazole) Janssen Pharmaceuticals has recently released Sporanox® (itraconazole) in an IV formulation. It is recommended in the treatment of potentially life-threatening blastomycosis, histoplasmosis, and aspergillosis infections refractory to amphotericin B or intolerant of first-line therapy. This new injectable form gives itraconazole the advantage of two dosage forms, allowing IV to oral switching when appropriate. It is available in a kit that includes a 25ml vial of itraconazole and a 50cc bag of normal saline. back to top

Medication Withdrawal Propulsid® On March 23, 2000, Janssen Pharmaceuticals announced a limited-access program will be initiated for Propulsid® tablets and suspension, and that the product will no longer be marketed in the United States. These changes are being implemented secondary to the agent being associated with 341 reports of arrhythmias and 80 deaths. Under the new program, Propulsid® will remain available to appropriate patients for whom other therapies are not effective and who meet clearly defined eligibility criteria. Information on the limited-access program will be sent to physicians across the country in April, and enrollment will begin May 1. However, to assure that the medication is available to patients during the transition, distribution will continue until July 14, and the product will remain in pharmacies until mid August. For additional medical information concerning Propulsid® , professionals may contact the Janssen One to One Customer Action Center at 1-800-526-7736. back to top

Transplant 2000 Meeting Held in Chicago May 13-17 The American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST) are having the first joint meeting of these two societies in May 2000. At the meeting a variety of formats are planned that will encourage the exchange of scientific and clinical information. The meeting will be held at the Sheraton Chicago Hotel and Towers in Chicago, Illinois during May 13-17, 2000. For information, please contact the ASTS National Office at 703-414-3033 or the AST National Office at 856-608-1104. back to top

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.