Practical Issues for Dietitians SUPPLEMENTAL SLIDES Presented by David B. Goldwater R.Ph Clinical Consultant Pharmacist March 31, 2011

2 CONTENTS MEGACE-ES ADVERSE EFFECTS PROGRAF

3 MEGACE & ADRENAL INSUFFICIENCY Source: Am J Geriatr Pharmacother 2008; 6:167–172

4 MEGACE & ADRENAL INSUFFICIENCY MEGACE & ADRENAL INSUFFICIENCY Source: Am J Geriatr Pharmacother 2008; 6:167–172 FOCUS OF CONCERN  Malnourished older patients who are given Megestrol acetate could be at risk for adrenal insufficiency.  It might be difficult to detect because the signs and symptoms are subtle. CASE STUDY  In Kansas City, Missouri, an 80-yearold woman with Dyspnea was being treated for major depression with psychotic features. Her physical functioning had declined.  Because she was losing weight, Megestrol acetate was prescribed to stimulate her appetite  Because she was losing weight, Megestrol acetate was prescribed to stimulate her appetite.

5 DURING HOSPITALIZATION  Her Dyspnea worsened. She was transferred to the intensive-care unit, where she was intubated. Her blood pressure dropped. a cosyntropin stimulation test, was performed to exclude adrenal insufficiency.  After infectious, cardiac, and neurological causes of hypotension were ruled out, a cosyntropin stimulation test, was performed to exclude adrenal insufficiency.  IT INDICATED A SUBOPTIMAL RESPONSE.  The medication was discontinued, and steroid replacement was initiated.  Blood pressure returned to normal, and the patient slowly improved.  She was weaned from the ventilator several weeks later.

6 OUTCOME  Two months later, her respiratory function improved, and cosyntropin stimulation test findings were normal.  Chronically ill, malnourished elderly patients with adrenal insufficiency may experience depression and reduced appetite, making the diagnosis difficult.  In this case, adrenal insufficiency was not suspected at first because the presentation was unusual,  The patient ’ s clinical history was complicated by other illnesses, and she had NOT been using Megestrol for a long time.

7 MEGACE-ES CONCLUSION/ RECOMMENDATION  For patients who need more than 12 weeks of treatment with Megestrol …...  Free cortisol levels should be checked at 12 weeks and biweekly thereafter. THE RESEARCHERS RECOMMEND:  During periods of illness( in patients receiving Megestrol) ……..  Consider EMPIRICAL THERAPY with stress doses of corticosteroids  Do not D/C Megace abruptly. Always taper gradually GO BACK TO SLIDE # 66

8 Implications for Drug Abuse An Interesting Drug-Alcohol Interaction

9 An Interesting Drug-Alcohol Interaction **Implications for Drug Abuse** Published in Journal Watch General Medicine January 31, 1992 Citations: DiPadova C et al. Comparison with other H2-receptor antagonists. JAMA 1992 Jan  A study measuring the effects of Ranitidine (Zantac ® ) and Cimetidine (Tagamet ® ) on the bioavailability of ethanol suggests that drinking with these drugs is NOT a wise choice because ……….  RANITIDINE AND CIMETIDINE INCREASE BLOOD ALCOHOL LEVELS.

10 An Interesting Drug-Alcohol Interaction **Implications for Drug Abuse**  Researchers tested the blood alcohol levels of 20 healthy male volunteers (mean age, 35)  During a baseline period and after a one- week course of EITHER  Ranitidine (300 mg/d),  Cimetidine (1000 mg/d) or  Famotidine (Pepcid)  Before each test, the subjects received Oral or intravenous alcohol equivalent to:  1 beer or 1 glass of wine.

11 RESULTS  In subjects given alcohol intravenously, none of the three drugs significantly increased alcohol bioavailability.  Among subjects taking alcohol ORALLY, bioavailability increased significantly with Ranitidine and Cimetidine NOTFamotidine.  ……..but NOT with Famotidine.

12 RESULTS  The authors speculate that Ranitidine and Cimetidine affected the absorption of oral doses because they INHIBIT gastric alcohol dehydrogenase activity.  However ……. Famotidine (Pepcid ® ) has NO effect on this enzyme!  Don ’ t confuse with Prilosec ® (omeprazole which is a PPI and not an H2 Blocker)  In patients with regular but moderate alcohol use, Famotidine (Pepcid ® ) may be a preferable H2- blocker

13 A AA ABUSE POTENTIAL FOR THIS INTERACTION:  This study indicates the need for extreme caution when drinking alcohol with Cimetidine or Ranitidine, particularly before driving!  As recreational drinking is an ORAL event ……………….  This interaction may be intentional in people who want to get inebriated on fewer drinks!

14 ….Timing is Everything! Prograf® (tacrolimus):

15 Prograf® (tacrolimus): INDICATION  Tacrolimus is an immunosuppressive agent derived from the fungus Streptomyces tsukubaensis.  Originally found in a soil sample taken from the base of Mt. Tsukuba in Japan.  Tacrolimus has been studied in patients receiving heart, kidney, liver, lung, pancreas, small bowel, or bone marrow  Tacrolimus has been studied in patients receiving heart, kidney, liver, lung, pancreas, small bowel, or bone marrow transplants.

16 P PP Prograf® (tacrolimus)  Effective in graft rejection prophylaxis and in the management of acute and steroid- or cyclosporine-resistant transplant rejection.  Tacrolimus is an alternative to cyclosporine immunosuppression and is10—100 times more potent than cyclosporine

17 P PP Prograf® (tacrolimus)  Administer at approximately the same time each day. REASON  If given WITH FOOD or WITHIN 1 HOUR OF A MEAL, especially high-fat meals, results in significantly decreased absorption.

18 Goals for Scheduling this drug in relationship to meals  Consistency is important TO MINIMIZE ANY Variations in bioavailability.  Administer consistently with OR without food.  Ask resident what time of day they have been taking this drug at home in relationship to meals times and what type of meal.  If possible attempt to accommodate the same schedule.