Volume 25, Number 1 January 2011 Drugs & Therapy B N U N L N L N E N T N I N N

MEDICATION SAFETY FORMULARY UPDATE The Pharmacy and Therapeutics DTaP and Tdap: Understanding the letters Committee met November 16, 2010. here has been much confusion to be given as the initial immunization. 2 drugs were added in the Formu- T among many health care practitioners Tetanus is the main ingredient in Tdap. lary, and none were deleted. 8 prod- regarding the combination vaccines for The concentrations of each component ucts were designated nonformulary diphtheria, pertussis and tetanus. Hun- in the vaccines vary largely between their and not available. 2 interchanges, 1 dreds of mix-ups, including one involving uses and even slightly between manufac- restriction, and 1 product extension 80 clinic patients, have been reported to turers within the same use. In the DTaP were approved. the ISMP Medication Errors Reporting vaccine, the diphtheria toxoid amount Program and many more may go unre- ranges from 6.7–25 Lf units, the tetanus ported or even unnoticed.1 The similar toxoid ranges from 5–10 Lf units, and the initials and letters lend themselves to pertussis toxin ranges from 10–46.8 mcg. ◆ ADDED mix-ups in ordering, dispensing, and In the Tdap vaccine the diphtheria toxoid administration of these products. amount ranges from 2–2.5 Lf, the tetanus Dihydroergotamine Injection Many combinations exist using the toxoid is 5 Lf, and the pertussis toxin (generic by Paddock Laboratories) diphtheria toxoid, tetanus toxoid, and ranges from 2.5–8 mcg. Telavancin acellular pertussis vaccine.2 For most Children under the age of 7 who are (Vibativ® by Astellas Pharma)* patients, trivalent combination products given Tdap in the initial immunization are the preferred agents due to their series may not respond adequately and *Restricted to ID or Antimicrobial Management Team approval convenience and coverage. Immuni- may need to be revaccinated. Adults zation is recommended to begin as a who receive the DTaP vaccine with ◆ DELETED 5-injection series using a combination higher antigen quantities do not need vaccine starting at 2 months and finish- revaccination but may have more None ing at 4–6 years. Booster vaccinations adverse effects from the vaccine and with the combination should be given at have an increased chance of a sore ◆ NONFORMULARY AND age 11–12 years and once as an adult.3 arm at the vaccination site. NOT AVAILABLE The products used for these vacci- Using brand names along with the Aliskiren (Tekturna®) nations at Shands at UF are the DTaP generic initials may help alleviate the and Tdap. Some key differences exist confusion between these products. The ® Calcipotriene Foam (Sorilux ) between these products that make them brand names of the DTaP product with Capsaicin 8% Patch (Qutenza®) suitable for different age groups. higher antigen levels are Daptacel®, The DTaP vaccine is used for induc- Infanrix®, and Tripedia®. Only Tripedia® Drospirenone-Ethinyl ing active immunity against diphtheria, is stocked for inpatient use. The brand ® estradiol-Levomefolate (Beyaz ) tetanus, and pertussis in infants and names of the Tdap product with lower ® ® Norethindrone acetate-Ethinyl children up to the age of 7 years. The antigen levels are Boostrix and Adacel . ® estradiol-Ferrous fumarate capital “D” and “P” in the name indicate Only Adacel is stocked for inpatient (Lo-Loestrin Fe®) higher antigen quantities of diphtheria use. When ordering, dispensing, or ad- toxin and pertussis vaccine than the ministering the vaccine, remember the Pegloticase (Krystexxa®) Tdap vaccine. The DTaP product is con- age differences between the vaccines Risedronate ER Tablet traindicated in children under the age of and that big letters are for little kids. (Atelvia®)† 6 weeks due to the fact that it may not By Robyn Keen, PharmD be immunogenic in that age group. It is REFERENCES ® Sibutramine (Meridia )† also contraindicated after 7 years of age 1. ISMP. DTaP-Tdap mix-ups now affecting hundreds of †Patients may NOT use their own due to a decreased risk of pertussis in patients. ISMP Nurse Advise-ERR. 2010;8(10):1-2. this population and an increased risk of 2. Grabenstein JD. ImmunoFacts:Vaccines and Immunologic supply Drugs. St. Louis, MO:Wolters Kluwer Health; 2008. adverse effects, such as a sore arm. An 3. 2010 CDC Child and Adolescent Immunization Sched- ◆ INTERCHANGES increased amount of antigen is needed ules. Accessed December 1, 2010 at http://www.cdc.gov/ for initial immunization to provoke a vaccines/recs/schedules/child-schedule.htm Levothyroxine proper immunogenic response. (generic interchange) The Tdap product contains reduced ◆ Mycophenolate mofetil (generic) amounts of diphtheria toxin and pertus- for CellCept® sis vaccine, as indicated by the lower INSIDE THIS ISSUE case “d” and “p.” This product is for ◆ Azithromycin vs erythromycin booster shots for adults and children ◆ (continued on next page) over the age of 7 years and does not Bulletin enters 25 years create enough immunogenic response Formulary update, from page 1 with hemiplegic or basilar migraine, a black box warning about potential patients with impaired hepatic or renal fetal risks. Precaution should also be ◆ CRITERIA-FOR-USE CHANGES function, or women who are pregnant. taken when prescribing telavancin to Nausea and vomiting are the most patients with a prolonged baseline ® Aztreonam (Azactam )* frequently reported adverse events as- QTc interval or taking drugs known to *Restricted to ID or Antimicrobial sociated with DHE. DHE should only be prolong the QT-interval. Management Team approval after used in patients who have first received The acquisition cost for telavancin 1st dose an antiemetic. is approximately $150 per day (for a Antivenin Micrurus fulvius, Telavancin is a lipoglycopeptide 70-kg patient), which is less than the Equine (North American Coral derivative of vancomycin that received alternatives currently in the Formu- Snake Antivenin)‡ FDA approval in September 2009 for lary, excluding vancomycin and tige- the treatment of adult patients with cycline. Telavancin was added in the ‡Expiration date extended to complicated skin and skin structure Formulary and restricted to Infectious October 31, 2011 infections (cSSSI) caused by susceptible Diseases or the Antimicrobial Man- gram-positive bacteria. It is currently agement Program for the management Dihydroergotamine (DHE) is a undergoing FDA review for the treat- of gram-positive infections in patients serotonin (5-HT) agonist that has ment of hospital-acquired pneumonia who fail or who are intolerant to other affinity for 5-HT1Da and 5-HT1Db recep- (HAP). Telavancin’s spectrum of activity therapies (ie, vancomycin). tors located on intracranial blood is similar to vancomycin, with activity Aliskiren is a direct renin inhibitor vessels and on sensory nerve endings against a wide range of aerobic and an- with a labeled indication for the treat- of the trigeminal system. There are aerobic gram-positive bacteria, includ- ment of hypertension. Aliskiren blocks 2 theories behind its mechanism ing some multidrug-resistant strains. the renin-angiotensin-aldosterone for treatment of acute migraines: Telavancin has a dual mechanism of system at the first step. 5-HT1D-mediated vasoconstriction of action: inhibition of peptidoglycan Adverse events are similar to intracranial blood vessels and 5-HT1D- synthesis and disruption of membrane angiotensin-converting enzyme (ACE) mediated inhibition of pro-inflamma- potential. This dual mechanism ac- inhibitors and angiotensin receptor tory neuropeptide release from the counts for its enhanced activity as well blockers (ARBs), including cough, trigeminal system. as rapid bactericidal properties. hyperkalemia, and the possibility of DHE was approved by the FDA in Telavancin has been compared to angioedema. Dose-related diarrhea 1946 for use in migraine and cluster vancomycin for the treatment of cSSSI has been reported. headaches. DHE was listed in the and HAP in several non-inferiority stud- Although there are currently no con- Formulary until 1993 when it was ies. For the treatment of cSSSI, tela- traindications for aliskiren, it should removed after the FDA approval of vancin was compared to vancomycin not be used in pregnancy or concomi- sumatriptan, which is more specific in 2 parallel, randomized, double-blind, tantly with cyclosporine or itracon- for central serotonin receptors and controlled, phase III trials (known as the azole. Because CYP 3A4 metabolizes has been associated with less nausea ATLAS trials). Patients received either aliskiren, drug interactions may be a and vomiting. telavancin or vancomycin for 7–14 days. concern. No renal adjustment is neces- DHE is still indicated for the acute Telavancin was shown to be non-inferi- sary, but caution is advised in those treatment of migraine and cluster or to vancomycin based on clinical cure with renal impairment. headaches. Its labeled dosage is rates. In a subanalysis of the ATLAS tri- Studies evaluating the blood 1 mg (ie, 1 mL) intravenously (IV), als, clinical cure rates in the telavancin pressure-reducing ability of aliskiren intramuscularly (IM), or subcutane- treatment group were lower in patients have demonstrated clinically equal ously (SQ), but it is usually given IV. with impaired renal function, defined as reduction in blood pressure in com- The dose can be repeated at 1-hour a creatinine clearance (CrCl) less than parison to ACE inhibitors, ARBs, and intervals but should not exceed 3 mg 50 mL/min, compared to patients with hydrochlorothiazide. No studies have (3 mL) for IM or SQ injections or 2 mg normal renal function. The ATTAIN evaluated the cardiovascular benefits (2 mL) for IV injections. DHE is not studies were randomized, double-blind, of aliskiren. indicated for chronic use due to pos- phase III trials in patients with HAP The cost of the aliskiren is substan- sible fibrotic complications. secondary to suspected or documented tially greater than the cost of the ACE Most of the trials for DHE are small gram-positive pathogens. Once again, inhibitors that are currently listed in and have poor generalizability. The telavancin was non-inferior to vanco- the Formulary, but similar to the cost authors of a 2005 meta-analysis con- mycin. Telavancin has also been used of the ARBs. cluded that DHE, alone, was not as off-label for the treatment of bacteremia Aliskiren offers no advantage over effective as sumatriptan or phenothi- and endocarditis. ACE inhibitors or ARBs. It costs more azines; however, DHE in combination Telavancin has predictable linear without demonstrating superiority in with an antiemetic was as effective pharmacokinetics that support once- blood pressure reduction or improved as opiates, ketorolac, or valproate. daily dosing. The labeled dosage of outcomes. Additionally, its safety The results of 2 studies comparing telavancin for cSSSI is 10 mg/kg IV profile is still not fully known, since it DHE with sumatriptan suggested that every 24 hours for 7–14 days. The actual is the first drug in a new category of sumatriptan and DHE are both effec- duration of therapy should be deter- drugs. tive in treating migraine headaches, mined by the patient’s infection, clinical Aliskiren was designated nonfor- however, sumatriptan works faster. status, and progress. Renal function mulary and not available; however, One head-to-head study reported more should be monitored closely and dosage patients may use their own supply of migraine recurrence within 24 hours adjustments are required in patients aliskiren from home if it is ordered. with sumatriptan compared with DHE. with impaired renal function. Rapid in- Sorilux® is a foam form of calcipo- Use of DHE is contraindicated in fusions can lead to Red-man Syndrome; triene with a labeled indication for the patients taking strong CYP 3A4 in- thus, telavancin should be administered topical treatment of plaque psoriasis. hibitors, patients with ischemic heart over 60 minutes to reduce this risk. The Calcipotriene is a vitamin D3 analog. disease, patients with uncontrolled most common adverse events reported Calcipotriene cream is rarely used hypertension, patients who have tak- are taste disturbance, nausea, vomiting, nonformulary (ie, 3 patients in the last en 5-HT1 agonists or other ergotamine and foamy urine. The drug is classified year) but may offer an alternative. products in the last 24 hours, patients as pregnancy category C and carries (continued on next page) 2 Formulary update, from page 2 Pegloticase is an injectable, recom- Sibutramine has never been listed Qutenza® patch is a high-concentra- binant, pegylated form of urate oxidase in the Formulary. Sibutramine was tion (8%) transdermal form of capsa- enzyme. It decreases uric acid concentra- designated nonformulary and not icin with a labeled indication for the tions by converting uric acid to allantoin, available and patients cannot use their management of pain associated with which is benign and can be excreted in own supply. postherpetic neuralgia (PHN). Qutenza® the urine. It is similar to rasburicase (Eli- Levothyroxine is a synthetic is 80 to 320 times more potent than tek®), which is also a recombinant form version of the endogenous thyroid over-the-counter capsaicin cream, of urate oxidase. Rasburicase, which is hormone tetraiodothyronine (T4). It which is available as 0.025% and 0.1%. listed in the Formulary, is not pegylated is used as replacement therapy for The high concentration of capsaicin in and has a labeled indication for the patients with hypothyroidism. Qutenza® causes a brief period of acute initial management of hyperuricemia as- In August 1997, the FDA an- pain, followed by a prolonged period sociated with tumor lysis syndrome. Ras- nounced that oral drug products of decreased nerve sensitivity. It takes buricase is restricted to use by oncology containing levothyroxine were new time for nerves to re-innervate, thus, prescribers for tumor lysis syndrome. drugs, requiring drug companies the long period between applications. Pegloticase’s labeled indication is for to submit a New Drug Application Qutenza® is applied for only 60 minutes the treatment of gout that is refractory (NDA). Currently, there are 7 brand every 3 months. to conventional therapy. The IV dose is name and 2 generic levothyroxine In addition to being expensive, this given every 2 weeks. It is not clear how products available on the market. product is difficult to use (eg, topical an- much longer pegloticase inhibits urate In Florida, levothyroxine has been esthetic and systemic pain medications oxidase compared with rasburicase. on and off the Negative Formulary for must be used prior to administration; it While pegloticase is effective in de- several years. Generic manufacturers must be handled only with nitrile [not creasing uric acid levels within 6 hours have argued that there is no differ- latex] gloves; must be administered by of administration, it has been associated ence between generic and brand a healthcare professional). Qutenza® will with acute gouty flares during initiation. name levothyroxine products, while not be acquired for inpatient use and Elevated uric acid levels (>6 mg/dL) are manufacturers of brand name levo- its application should be deferred to the associated with increased risk of hyper- thyroxine products, as well as certain outpatient setting. sensitivity reactions as well as infusion thyroid and endocrine societies, Beyaz® is a low-dose, monophasic reactions. maintain that there is a therapeutic oral contraceptive with labeled indica- Initiation of pegloticase caused a difference. The Negative Formulary tions for the prevention of pregnancy gouty flare in 2/3 of patients in clinical is not applicable to the inpatient set- and for the following indications in trials. Therefore, it is recommended that ting. The P&T Committee determines women who choose to use an oral there be 1 week of prophylaxis with which products can be interchanged. contraceptive for contraception: the colchicine and/or NSAIDs to prevent The FDA’s Approved Drug Products treatment of premenstrual dysphoric these gouty flares. Thus, acute use in With Therapeutic Equivalence Evalu- disorder (PMDD), treatment of moder- the inpatient setting could be harmful. ations, better known as the “Orange ate acne, and to raise folate levels. Pegloticase was designated nonformu- Book,” contains a list of currently Drospirenone, which is an analogue lary and not available for inpatient use. approved drug products, as well as of spironolactone, is the progesterone Atelvia® is a once-weekly delayed- therapeutic equivalence evaluations, component of Beyaz®. It has antiminer- release tablet formulation of the for products with multiple sources, alocorticoid and antiestrogenic proper- bisphosphonate risedronate with a like levothyroxine. Therapeutically ties and is intended to improve premen- labeled indication for the treatment of equivalent levothyroxine products strual symptoms, including negative postmenopausal osteoporosis. It has the share a 3-character code (ie, AB1, mood, water retention, and increased same restrictive administration require- AB2, AB3, etc.). The number in appetite. Drospirenone may increase ments as all oral bisphosphonates (ie, the 3-character code refers to the potassium levels in some patients. take in the morning with at least 120 mL reference-listed drug (RLD) that other Ethinyl estradiol is the most com- of plain water and do not lie down for 30 products are compared with. Accord- mon estrogen component of combi- minutes). Irritation of the upper GI tract, ing to the Orange Book, not all levo- nation oral contraceptives. Beyaz® even esophageal ulceration, is possible if thyroxine products have been shown contains a relatively low dose of ethinyl risedronate is not administered properly. to be equivalent to each other; how- estradiol (20 mcg). Levomefolate is Therefore, Atelvia® was designated ever, Mylan’s levothyroxine sodium is also known as L-methylfolate, and is nonformulary and not available. Like equivalent to all reference listed drug the biologically active form of folic acid. all bisphosphonates, patients will not products of levothyroxine (ie, brand Beyaz® was designated nonformulary be allowed to use their own supply of name levothyroxine products). and not available. Patients should use Atelvia® for safety reasons. The only oral There have been several studies their own supply from home. The only bisphosphonate listed in the Formulary looking at the bioequivalence and combination oral contraceptive listed is alendronate, which is restricted to therapeutic equivalence of the differ- in the Formulary is a generic version of use in patients who have been in the ent levothyroxine products. Newer Lo Ovral®, which contains the progestin hospital for at least 7 days. The alendro- studies that follow current FDA norgestrel and ethinyl estradiol. nate order must specify administration guidelines for bioequivalency studies Lo Loestrin Fe® is a combination oral instructions consistent with the labeling have found that levothyroxine prod- contraceptive with the lowest dosage and patients must be able to comply ucts fall within the FDA’s definition of of estrogen (ethinyl estradiol 10 mcg) of with this method of administration. bioequivalent. any product currently marketed in the Sibutramine is primarily a nor- The cost difference between United States. It contains half the estro- epinephrine and serotonin reuptake different levothyroxine products is gen in Loestrin 24 Fe®. It also contains inhibitor, which was thought to enhance negligible. However, when consider- the progestin norethindrone acetate satiety. This prescription weight-loss ing cost implications from the view of and ferrous fumarate as an oral iron drug was recently withdrawn from the a hospital’s Formulary, storage and supplement. market when postmarketing surveillance packaging of the medication, become Like Beyaz®, the Lo Loestrin Fe® was data showed a higher rate of cardiovas- factors in the decision. Availability designated nonformulary and not avail- cular events (eg, non-fatal MIs, non-fatal in unit-dose packaging has resulted able and patients should use their own strokes, and death). in the use of brand name Synthroid®, supply from home. (continued on next page) 3 Formulary update, from page 3 but it is not always available. We have been routinely converting patients from other brands and generics to Synthroid® for years without any patient- noticeable impact. Therefore, the P&T Committee determined that levothyroxine products can be interchanged to any marketed levothyroxine product. Preference will be given to products that are available in a unit-dose for- mat (eg, Synthroid®), but any unit-dose product could be substituted while a patient is hospitalized. Prescrib- ers may choose to prescribe a specific brand or generic upon discharge and should consider this as part of the medication reconciliation process. Mycophenolate mofetil is an immunosuppressive drug that was originally approved under the brand name CellCept®. There are now A-rated generic equivalents for CellCept® listed in the Orange Book. Until recently, Roche/Genentech matched the generic pricing. They recently terminated this agreement and the brand name costs increased 10-fold. There are no generic equivalents for the injection or oral sus- pension. If we do not use a generic mycophenolate capsule, pharmaceutical costs will increase approxi- mately $150,000. Expenses will increase an additional $150,000 for mycophenolate injection and suspension. Thus, without the switch to the generic capsule, phar- maceutical expenditures would increase $300,000. By policy, generic mycophenolate mofetil capsules will be used in the inpatient setting. Patients are admit- ted to the hospital already receiving the generic prod- uct. In the past, we would have switched them from the generic to the brand. This has been done without any clinical consequences. Aztreonam is a monobactam antibiotic with activ- ity against gram-negative bacteria. Compared with other options, like beta-lactam antibiotics, it is far less potent. Aztreonam is generally reserved for use for the treatment of gram-negative infections (including Pseudomonas) when patients cannot tolerate a beta- lactam because of Type-1 hypersensitivity reactions. Unfortunately, beta-lactam allergies are often poorly documented and/or inaccurate, which may lead to pro- viding suboptimal antimicrobial therapy. Aztreonam is overused, which contributes to the development of resistance (ie, poor sensitivities) to this niche anti- biotic. This could result in poor results when aztreo- nam is used empirically to treat suspected infections like Pseudomonas. Therefore, aztreonam has been restricted to approv- al by Infectious Diseases or the Antimicrobial Manage- ment Team after the first dose has been administered. This balances the need for rapid use in the setting of a suspected gram-negative infection, while preventing more than one dose. Coral snake antivenin has been used as the antidote to the neurotoxin in coral snake bites. Coral snakes are common to this part of Florida. Wyeth originally announced that there would be no more coral snake antivenin after the end of October 2008, when the last remaining product was scheduled to go out-of-date. Product has not been manufactured for several years. The last 2 years, the FDA granted the remaining product extended dating. Recently, the FDA again extended the dating for the remaining lots of coral snake antivenin until October 31, 2011. Once this product is gone, there will no longer be a commercially available antidote and patients will have to be man- aged with symptomatic support.

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EDITORIAL Twenty-five years of Bulletin he Drugs & Therapy Bulletin is entering its 25th T year of publication. I have been the editor and primary author of the Bulletin for those 25 years. I have received favorable feedback and some criticism for its content; regardless, I appreciate those who take the time to read the Bulletin. The Bulletin is the primary written method of communicating decisions made by the Pharmacy and Therapeutics Committee. The P&T Committee is the medical staff committee that is the formal line of communications between the hospital and the medi- cal staff regarding drug-related matters. If medical staff members do not receive the Bulletin or read it, we cannot do an effective job of communicating. If you are aware of medical staff members who should be added to the mailing list, please let me know. Throughout the last 25 years, I have tried to ex- plain why the P&T Committee makes its decisions. Why was a drug added or not added in the Formu- lary? Why was a drug’s use restricted? Why was a drug use policy adopted? You may not agree with the P&T Committee’s decisions, but you should under- stand the rationale for those decisions. The newsletter also contains articles that are intended to be informative but brief. I welcome feedback on any of these articles. Please send any comments to my email address ([email protected]). If you have ideas for topics that should be covered in the Bulletin, I would appreciate the suggestions. The best topics would have broad appeal to all practice areas and would focus on promoting safe and cost- effective use of medications. Any suggestions that would make the Bulletin more informative or useful are welcomed. By Randy C. Hatton, PharmD, FCCP, BCPS

CONTROVERSIES Is erythromycin preferred to azithromycin as a prokinetic? n last month’s issue of the Bulletin, the article, Oral I Erythromycin for Gastroparesis: The More Stable Choice?, stimulated some controversy.1 A recently published, retrospective, nonrandomized, quasi-experimental study done at UF suggests that azithromycin and erythromycin given intravenously were equally effective at stimulating gastric emptying as mea- sured by technetium-egg gastric emptying scintigraphy (GES).2 The study was done on 60 patients with symp- toms of gastroparesis undergoing GES showing similarly accelerated gastric emptying with IV injections of each medication after a delayed emptying was diagnosed by GES. Drs. Moshiree and Toskes suggest azithromycin is preferred because of the longer duration of effect with azithromycin (with a longer duration of antral contractions seen during antroduodenal manometry), a longer half-life requiring fewer doses needed per day improving patient compliance, better adverse-effect profile (eg, less risk of QT prolongation and gastrointestinal adverse effects), 5 5 (continued on page 6) Drugs & Therapy SHANDS NON-PROFIT ORG. B N U N L N L N E N T N I N N Shands at the University of Florida U.S. POSTAGE DRUG INFORMATION SERVICE PAID GAINESVILLE, FL Volume 25, No. 1 January 2011 PO Box 100316 PERMIT NO. 94 This publication is produced by the Gainesville, FL 32610-0316 Drug Information and Pharmacy Re- source Center under the direction of the Department of Pharmacy Services and the Pharmacy and Therapeutics Committee. EDITOR, DRUGS & THERAPY BULLETIN Randy C. Hatton, PharmD DIRECTOR, PHARMACY SERVICES Alan Knudsen, MS, RPh CHAIRMAN, PHARMACY & THERAPEUTICS COMMITTEE Ricardo Gonzalez-Rothi, MD EDITING, DESIGN, & PRODUCTION Shands HealthCare’s Publication Svcs. © Copyright 2011. All rights reserved. No portion of the Drugs & Therapy Bulletin may be reproduced without the written consent of its editor. FOR MORE INFORMATION, VISIT US ONLINE http://shands.org/professionals/ druginfo/bulletin.asp

Controversies, from page 5 cin and azithromycin) is the risk of the medication over time is a known and lack of CYP3A interactions with overuse, which could contribute to problem with chronic use of erythro- azithromycin as compared with eryth- resistance for antibiotics that are still mycin. Also, despite the known fact romycin. Erythromycin has been associ- widely used (especially in the case of that erythromycin is currently the most ated with an increased risk of sudden azithromycin). For example, azithromy- potent prokinetic for use in gastropa- cardiac death if given concomitantly cin is commonly used for the treatment resis, it is still not FDA-labeled for that with other medications metabolized of community-acquired pneumonia and indication. The only drug that is FDA- through the P450 pathway.3 Additional is still listed in the most recent treat- approved is metoclopramide, which research like that being done here at ment guidelines.5 Azithromycin’s long now has a black-box warning due to UF will help determine the relative half-life and low intracellular levels risk of tardive dyskinesia. long-term efficacy and safety of these may contribute more to resistance than Finally, erythromycin can interact agents. other macrolide antibiotics. Motilin with medications such as statins, SSRIs, In a case-series of 30 patients com- agonists without the antibiotic proper- calcium channel blockers, antifungal paring erythromycin (250 mg IV) to ties are currently being investigated medications, warfarin, and drugs that azithromycin (250 mg IV [n=15] or 500 for use in patients with gastroparesis, prolong the Q-T interval. For those mg IV [n=15]), antroduodenal manom- 2 of which are in Phase II trials. patients who may experience serious etry showed statistically greater mean The main point of last month’s news- interactions, azithromycin is the more amplitude of antral contractions, longer letter article was the 10-day stability rational choice since it is the least duration of antral contractions, and for azithromycin suspension compared arrhythmogenic option for treatment of a greater motility index (a calculated with 35-day stability for erythromycin this chronic and debilitating condition. 1 measurement of motility) with azithro- suspension. Studies examining longer REFERENCES mycin compared with erythromycin.4 stability for azithromycin suspension 1. Hatton RC. Oral erythromycin for gastroparesis: the more are needed. Studies have not been stable choice? Drugs & Therapy Bulletin 2010;10:1. This study, however, was nonrandom- 2. Larson JM, Tavakkoli A, Drane WE, et al. Advantages ized, open-labeled, and did not mea- done since chronic use of azithromy- of azithromycin over erythromycin in improving the gastric sure any symptomatic improvement. cin is not a labeled indication. Now, emptying half-time in adult patients with gastroparesis. J Neurogastrenterol Motil 2010;16:407-13. Currently, Moshiree and Toskes have patients must return to their outpatient 3. Ray WA, Murray KT, Meredith S, et al. Oral erythromycin an ongoing randomized control trial pharmacy every 10 days to obtain a and the risk of sudden death from cardiac causes. N Engl J Med 2004;351:1089-96. comparing the efficacy of erythromycin freshly made supply of azithromycin 4. Moshiree B, McDonald R, Hou W, et al. Comparison of the versus azithromycin for the symptom- suspension. This can be a disadvan- effect of azithromycin versus erythromycin on antroduodenal tage for a chronic medication, when an pressure profiles of patients with chronic functional gastro- atic treatment of gastroparesis (show- intestinal pain and gastroparesis. Dig Dis Sci 2010;55:675- ing equivalence) funded through a Pilot alternate medication could be picked 83. Grant from the CTSI. up once a month. Also, it is not clear 5. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious dis- eases society of America/American thoracic society consen- Despite these ongoing trials, a whether tachyphylaxis, which often sus guidelines on the management of community-acquired known disadvantage for chronic use occurs with erythromycin, occurs with pneumonia in adults. Clin Infect Dis 2007;44:S27-72. 6 of these motilin agonists (erythromy- azithromycin. This lack of response to