Newsletter – July 2015 Does topical tacrolimus ointment enhance the efficacy of narrowband ultraviolet B therapy in generalized vitiligo? Written by: Irinel Finco ISU PharmD Candidate

Idaho Drug Information Center Idaho State University 921 S. 8th Ave, Stop 8092 Pocatello, ID 83209-8092 208-282-4689 [email protected] Rebecca Hoover, PharmD, MBA, Director, [email protected]

Location: Third floor Eli Oboler Library at ISU

Vitiligo is an acquired progressive disease in which the melanocytes are destroyed gradually, causing unpigmented areas on the skin. 1,2 It is not life threatening but it has a profound psychological impact, especially in people with darker skin color. It affects about 0.5-1% of the world population and about half the cases begin in childhood with a slight female predominance in childhood.2 Diagnosis of vitiligo is based upon medical and family history, clinical presence of depigmented patches of skin and sometimes biopsy or use of Wood’s lamp.2,3 There are a limited number of options in vitiligo treatment, and many physicians consider vitiligo a trivial cosmetic skin disorder and treatment a waste of time and effort, which discourages patients from seeking treatment. Although there is still no cure for vitiligo, many options are available that may lead to good results, especially if treatment is started early. Repigmentation therapies include: • Topical and oral corticosteroids • Topical calcineurin inhibitors • Ultraviolet light (PUVA and NB-UVB) • Skin grafting techniques, But the evidence for these therapies is limited, especially for long-term benefits and safety.1,4,5 Topical corticosteroids have been used since 1950 and had best results (75% of repigmentation) on sun-exposed areas, in dark skin and in recent lesions, but their side effects are skin trophy, telangiectasia, hypertrichosis and acneiform eruptions. Currently, there are no studies available on optimal duration of TCS therapy and on discontinuous applications that could improve the therapeutic index. Calcineurin inhibitors (CI) are used as an alternative to TCS for new, actively spreading lesions on thin skin where prolonged use of potent TCS is contraindicated, but few randomized trials showed beneficial results mainly in the head and neck region, both in adults and children. Most treatment centers currently consider NB-UVB as the first line treatment for generalized NSV due to its higher efficacy and lower risk of adverse SE, and treatment is usually given twice or three times weekly and is continued as long as there is ongoing repigmentation.

Newsletter – July 2015 Topical tacrolimus is a well-documented treatment for vitiligo and has been shown to compare favorably with super potent topical steroid, with less adverse effects. A controlled trial, left-right comparison study done in 2010, tried to establish the effect of combining topical tacrolimus to NB-UVB therapy in causing repigmentation in vitiligo lesions. The study concluded that addition of topical tacrolimus ointment to the NB-UVB regimen has an added benefit, leading to higher extent of repigmentation and a reduction in the number of NB-UVB treatments required to achieve the therapeutic effect. The problem with this study is the p value they used (p=0.5), which means that there could be up to almost 50% chance that the results are due only to random chance.6 In another controlled, randomized double blind study published in 2011, treatment with NB-UVB combined with tacrolimus ointment (0.1%) was compared with treatment with NB-UVB combined with placebo ointment, and it had really good results. Reduction in vitiligo target lesions were 42.1% on the tacrolimus side and 29% on the placebo side. So, evidently, authors came to the conclusion that NB-UVB combined with tacrolimus ointment (0.1%) once daily may be a favorable treatment option for vitiligo, especially if the distribution is limited. This was one of the fewer studies to contain a greater number of participants and it also included an assessment of disease impact on the patient and ability to cope. The problem with this study was that it was underpowered, they used only once daily application of tacrolimus when other studies used it twice daily and they also found no correlation between the number of NB UVB treatments and reduction in lesion area.7 All in all, these studies showed superior efficiency of combining different treatments over monotherapy, better results using NB-UVB combined with tacrolimus vs NB and placebo. Tacrolimus has a black box warning but given that most patients felt disappointed by previous conventional treatments they considered the possible risks related to treatment a secondary minor aspect in comparison with their disfiguring vitiligo. This patient perception is an indirect measure of the pronounced burden on the quality of life caused by vitiligo. So, based on these conclusions, I would recommend addition of tacrolimus 0.1% to NB-UVB treatment in patients over 15 years old with generalized stable nonsegmental vitiligo, but not for a period longer than six months. Further studies are necessary focusing on the optimal duration of therapy and long-term follow-up results.

APP REVIEW: ABOUT HERBS BY JODIE FALLOWS CREIGHTON UNIVERSITY PHARMD CANDIDATE 2016 About Herbs is a mobile application from Memorial Sloan Kettering Cancer Center and is a guide to botanicals, supplements, complementary therapies and more. Users can browse and search evidence based information including: clinical summary, constituents, mechanism of action, pharmacokinetics, warnings, adverse reactions, herb-drug interactions, herb-lab interactions, and references. Each topic can be viewed in two formats. One is intended for healthcare providers and the other for consumers.

The app’s features include:  Search by product name, service name, or medical condition  Save your favorite listings  Browse listings without an internet connection after the app has been downloaded  Pros: Good for questions you might be asked while working at a community pharmacy. Quick and easy to navigate. Cons: No a validated or well-known resource, so professional judgment should be used when referencing it. Currently this app is only available for iPhone devices. However their website is designed to work will with mobile devices and tablets and it should be possible to view and navigate their databases on non-apple products.

https://www.mskcc.org/cancercare/treatments/symptommanagement/integrativemedicine/herbs

Newsletter - July 2015 Question of the month Are artificial sweeteners a good option to replace sugars for patients to improve compliance with weight loss? Written by: Sylvia Ofori ISU PharmD Candidate 2019

Lower or no calorie sweeteners are helpful if patients do not use them as a pass to consume more calories. There have been recent articles published in assessing the effects of caloric sweeteners and lower - or - no calorie alternative on weight loss. A literature review adopted two study designs in evaluating the association between low calorie sweeteners (LCSs) and body weight. An observational study that examined LCSs from foods or beverages or as tabletop sweeteners proved no correlation between LCSs intake and body weight or fat mass. However, an identification of data from a randomized controlled trial showed that, the substitution of LCSs for regular calorie version resulted in a modest weight loss. Therefore, consuming less sugar is not a license to eat more. Artificial sweeteners are a better choice than sugar but that is not to say they are a healthy choice. They are safer than consuming large quantities of sugar because they do not raise blood glucose in patients with diabetes. It is important to encourage diabetes patients to choose foods without added sugar or sweeteners such as veggies, fruits, whole grains, and no fat or low - fat dairy. If they have a sweet tooth, advise them to look for a product that uses an FDA approved agent such as aspartame, saccharin, sucralose, acesulfame K, or neotame. Encourage patients to pick one they like because there is no evidence that one is safer than the other.

Toujeo Written by Brittany Hottel ISU PharmD Candidate TOUJEO is a long- acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. It was approved February 2015. Toujeo Solostar injection pen is 300 units/mL of insulin glargine in a 1.5 mL prefilled disposable pen with an onset of action that develops over approximately 6 hours. Toujeo is dose based upon type of diabetes, blood glucose levels and goals, as well as daily metabolic demands. It is a SubQ injection given once daily at the same time each daily. Just like other insulin injections the injection site should be rotated between spots on the abdomen, thighs, and if needed back of the arms. Blood glucose levels need to be closely monitored when changing to Toujeo or when initially starting it. Insulin pens are for a single patient and should never be shared. Monitoring of hypoglycemia, hypokalemia, and other electrolytes should be done just like with other insulins. Toujeo cannot be recommended to treat diabetic ketoacidosis and shouldn’t be used when patient is experience hypoglycemia. This form of Insulin can be useful in treating patients who are insulin resistance and don’t want to give multiple injections multiple times a day. Toujeo will allow these patients to be able to get more units of insulin per ml as well as being a long acting insulin will decreases number of injections.

Newsletter – July 2015

"HIGHLIGHTS OF PRESCRIBING INFORMATION." These Highlights Do Not Include All the Information Needed to Use TOUJEO Safely and Effectively. See Full Prescribing Information for TOUJEO. TOUJEO (insulin Glargine Injection) U-300, for Subcutaneous UseInitial U.S. Approval: 2015. N.p., n.d. Web. 20 May 2015.

Newsletter - July 2015 References Does topical tacrolimus ointment enhance the efficacy of narrowband ultraviolet B therapy in generalized vitiligo? 1. Lotti T, D'Erme AM. Vitiligo as a systemic disease. Clin Dermatol. 2014 May-Jun;32(3):430-4. 2. Taieb A, Alomar A, Böhm M, Dell'anna ML et al. Vitiligo European Task Force (VETF); European Academy of Dermatology and Venereology (EADV); Union Europe´enne des Me´decins Spe´cialistes (UEMS). Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br J Dermatol. 2013 Jan;168(1):5-19 3. Ho N, Pope E, Weinstein M, Greenberg S.et al. A double-blind, randomized, placebo-controlled trial of topical tacrolimus 0.1% vs.clobetasol propionate 0.05% in childhood vitiligo. Br J Dermatol. 2011Sep;165(3):626-32 4. Kovacs SO. Vitiligo. J Am Acad Dermatol. 1998 May;38 :647-66 5. Njoo MD, Westerhof W. Vitiligo. Pathogenesis and treatment. Am J Clin Dermatol. 2001;2(3):16781 6. Majid I. Does topical tacrolimus ointment enhance the efficacy of narrowband ultraviolet B therapy in vitiligo? A left-right comparison study. Photodermatol Photoimmunol Photomed. 2010 Oct;(5):230-4 7. Nordal EJ, Guleng GE, Rönnevig JR. Treatment of vitiligo with narrowband-UVB (TL01) combined with tacrolimus ointment (0.1%) vs. placebo ointment, a randomized right/left double-blind comparative study. J Eur Acad Dermatol Venereol. 2011 Dec (12):1440-3 Question of the month: Are artificial sweeteners a good option to replace sugars for patients to improve compliance with weight loss?

1. Miller, P., & Perez, V. (2014). Low-calorie sweeteners and body weight and composition: A meta-analysis of randomized controlled trials and prospective cohort studies. American Journal of Clinical Nutrition, 765-777. 2. Artificial sweeteners are a good option to replace sugar for diabetes patients with a sweet tooth. Pharmacist letter. February 08, 2013. Accessed on June 26, 2015 http://pharmacistsletter.therapeuticresearch.com/pl/Rumor.aspx?cs=STUDENT&s=PL &fpt=31&rtid=439&cat=4333 Toujeo 1. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9561d96-124d-48ca-982f0aa1575bff36. Accessed July 7, 2015.