NEWSLETTER 5.0

PHARMACY NEWSLETTER Hospital Melaka INTESTINAL BOWEL DISEASE (IBD) You are stronger than Crohn's CURRENT DRUG DRUG ISSUE SAFETY REVIEW Crohn's Disease Tumor Necrosis Factor Alpha Biologics: Infliximab and PAGE 1 - 3 (TNF): Kaposi's Sarcoma Adalimumab PAGE 4 PAGE 5 - 6 DISEASE NEW DRUG PHARMACY NEWS & UPDATE PROFILE EDUCATION ANNOUNCEMENT Esophageal and Budesonide Oral Bowel Preparation before Kursus Farmakoterapi 2022: Gastric Disease (Prolonged Release Colonoscopy: Pico-Salax® vs Gastroenterology & Hepatology Tablet) Fortrans® vs Oral Fleet® PAGE 7 - 8 Antibiotic Updates 2022 PAGE 9 PAGE 10 Kursus Penggunaan Ubat Secara Berkualiti PAGE 11 - 12

Page 1 CURRENT ISSUES HOSPITAL MELAKA PHARMACY NEWSLETTER CROHN'S Assessing disease activity, DISEASE severity and risk The disease severity of CD is categorized by the Harvey Bradshaw Index (HBI) as a simplified version of the Crohn's Disease Activity Index (CDAI). The index considers five parameters. For each parameter, a specific score is assigned, as shown in the following table. 4 Total score from above will determine the disease severity such as follow: Crohn’s Disease (CD) is a chronic trans-mural inflammatory condition, which can affect any part of the Gastrointestinal Tract (GIT), from mouth to anus. The damaged areas appear in patches that are next to areas of healthy tissue and the inflammation may reach through the multiple layers of the walls of the GIT1,2 . Treatment goal The treatment goal for CD is to achieve remission (endoscopic, histologic and clinical remission) by demonstrating complete mucosal healing. After clinical remission (i.e. IBD symptoms have resolved) has been achieved, the goal of management is to prevent clinical and endoscopic relapse.

Page 2 CURRENT ISSUES HOSPITAL MELAKA PHARMACY NEWSLETTER TREATMENT OF CD WITH BUDESONIDE PR, ORAL GLUCOCORTICOIDS, 5-AMINOSALICYLATES, SULFASALAZINE 3 ORAL BUDESONIDE PR 9mg Budesonide PR is indicated in adults for induction of remission in patients with mild to moderate active ulcerative colitis (UC) where 5-aminosalicylic acid (5-ASA) treatment is not sufficient or not tolerated. Budesonide PR is a corticosteroid with a high first-pass hepatic metabolism. Dose: 9 mg tablet in the morning, for up to 8 weeks. Oral glucocorticoids Oral glucocorticoids (eg. Prednisolone) are alternative agents for initial therapy in patients with mild Crohn’s disease involving ileum and/or proximal colon. Can be given to low-risk patients who do not respond to budesonide. However, patients who initially respond to oral glucocorticoids but cannot tolerate gradual tapering of prednisolone are no longer considered as low-risk and should reassigned to the moderate/high risk category. Initial dose of prednisolone: 40mg/day for 1 week. A gradual tapering down by 5- 10mg per week should be started with the goal of discontinuing the prednisolone over 1-2 months. 5-aminosalicylates (5-ASA) Use of 5-ASA for Crohn’s disease is controversial and is limited to use to patients with mild Crohn’s disease with limited ileocolonic involvement who prefer to avoid glucocorticoids. A slow release, oral 5-ASA agent is suitable for such patients, such as mesalazine. Sulfasalazine which is the prodrug of 5-aminosalicylate, is less useful for ileitis because colonic bacteria must cleave the drug to release the active 5-ASA moiety, so it is reserved for cases of colitis.

Page 3 CURRENT ISSUES HOSPITAL MELAKA PHARMACY NEWSLETTER TREATMENT OF CROHN’S DISEASE WITH BIOLOGICS: A N T I - T N F A G E N T S & B I O S I M I L A R5 Anti-TNF agents 3 anti - TNF approved for Infliximab and Adalimumab are preferred for induction of remission, while all CD: three anti-TNF agents are used to maintain remission. Infliximab (Remsima) is a chimeric IgG1 monoclonal antibody against tumor Infliximab, necrosis factor-alpha comprised of 75% human and 25% murine sequences, Adalimumab and which has a high specificity for and affinity to tumor necrosis factor-alpha. Certolizumab pegol. Adalimumab (Humira) is a recombinant human IgG1 monoclonal antibody directed against tumor necrosis factor-alpha and is administered by subcutaneous injection. Certolizumab pegol (Cimzia) is a humanized monoclonal antibody Fab fragment linked to polyethylene glycol that neutralizes TNF. The polyethylene glycol increases its plasma half-life and reduces requirement for frequent dosing, possibly reducing immunogenicity as well. Certolizumab is reserved as a second or third line anti-TNF agent in patients with Crohn’s disease who responded to Infliximab or Adalimumab and then lose response or become intolerant. Biosimilar Biosimilar is a copy which is similar but not identical to the reference or legacy product and is no longer under patent protection. Infliximab-dyyb (CT-P13) is a biosimilar to the original Infliximab. This biosimilar has shown equivalent clinical efficacy in patients with Crohn’s disease. The use of biosimilars for patients who are newly starting an anti- TNF agent may result in greater access to biologic therapy, however, more studies are needed on interchangeability and the risk of immunogenicity with these products. OTHER THERAPY: ANTI-DIARRHEAL MEDICINE & ANTIBIOTIC 3 Anti-diarrhea Antibiotic Antidiarrheal drugs are for patients not responding Antibiotics are generally not used for patients with completely to first-line therapy who have mild Crohn’s mild Crohn’s disease. disease without complications such as strictures. The data pertaining to the use of antibiotics for Antidiarrheal drugs are NOT for patients with moderate or treatment of active luminal Crohn’s disease has been severe Crohn’s disease or those at risk for bowel inconsistent. obstruction. It is unclear whether the efficacy of antibiotics is due to Examples of antidiarrheal drugs: Loperamide, treatment of an undetected pathogen, bacterial Cholestyramine or other bile sequestrants. overgrowth or and unsuspected microperforation. Antibiotics that are frequently utilized are metronidazole or ciprofloxacin.

Page 4 DRUG SAFETY HOSPITAL MELAKA PHARMACY NEWSLETTER Special points TUMOUR NECROSIS FACTOR ALPHA (TNF α ): of interest: KAPOSI’S SARCOMA  The National TNFα—Tumor necrosis KS– Kaposi’s sarcoma or also Kaposi Sarcoma had been Pharmaceutical classified into 4 types based Review factor alpha blocker is the known as Kaposi’s Sarcoma on aetiologies 7-8: Authority (NPRA) has treatment used to treat herpes virus (KSHV) is a received 314 ADR reports, chronic inflammatory disorder of A) Classis KS-originally with 556 described by Kaposi, adverse events disease such as plaque angioproliferative that need typically present in suspected to be middle or old age; attributable to prioriosis and rheumatoid infection with human herpes TNFα blockers 8-10. arthritis. virus (HHV-8) to develop 7.  However, for all Patients who take TNFα B) Endemic KS— TNFα blockers, no occurrence blockers are at the high risk prevalent among related to Kaposi's of serious infection as TNFα indugenous Africans sarcoma has been blocker are in Sub-Saharan Africa; documented locally 8-10. immunosuppresants which the immune system has C) Iatrogenic KS– Relat- ed with immunosup- becomes lower ability to pressive drug , com- monly among the fight infection6. recipients of organ transpant; On July 2011, The Food and The picture show Kaposi’s Drug Administration in U.S. Sarcoma on skin of AIDS D) Epidermic KS– ac- had updated the Boxed Warning for the all class of patient. quired immune TNFα to include the risk of infection from Legionella dificency syndrome and Listeria bacteria pathogens. (AIDS) associated. CONTEXT OF THE SAFETY ISSUE European Medicines Agency Initially, the signal of KS was of analysis and evaluation to (EMA) had shared the infor- identified for infliximab which include other TNFα blockers mation regarding the risk of based on the reported cases such as adalimumab, etaner- KS associated with TNFα in the national database of cept, certolizumab, and goli- blockers to National Spanish. mumab 8. Pharmaceutical Regulatory Agency (NPRA) in August Following a review of all All TNFα blockers are capable 2020 9. available evidence from case for the risk of KS following reports and the literature, the safety review by EMA. the EMA expanded the scope

Page 5 DRUG REVIEW HOSPITAL MELAKA PHARMACY NEWSLETTER TNF α INHIBITORS : INFLIXIMAB AND ADALIMUMAB Tumor Necrosis Factor and inflammatory bowel which includes the drugs (TNF) is an immune- disease. Etanercept, Infliximab, and modulating cytokine that Adalimumab, is used in the is required for immune TNF's activity is dependent treatment of a variety of processes. TNFs' unregu- on its two receptors, TNF inflammatory and immune lated activities can result receptor 1 (TNFR1) and diseases. in the development of TNF receptor 2 (TNFR2). inflammatory diseases. Blocking the interaction Although all of these rea- Excess TNFα expression in between TNFα and TNFRs gents work to disrupt the cells has been linked to the has proven to be an effec- interaction between TNF development of immune tive treatment for inflam- and its receptors, clinical diseases such as rheuma- matory and autoimmune trials revealed that Ada- toid arthritis, Crohn's dis- illnesses. limumab treatment out- ease, psoriatic arthritis, performed Etanercept and TNFα-targeting therapy, Infliximab 11. HISTORY OF ANTI-TNF α Antitumor necrosis factor- the past decades to treat 1998 by FDA was Inflixi- alpha (TNFa) agents inflixi- patients with IBD, even mab (Remicade), followed mab (IFX) and adalimumab those who had previously after 3 months by Etaner- (ADA) have altered the failed conventional thera- cept (Enbrel), Adalimumab clinical course of many py 12. (Humira) in December autoimmune diseases, 2002, Certolizumab pegol including inflammatory Currently, there are 5 (Cimzia) in April 2008 and bowel disease (IBD), psori- blockers of TNFa that the lastest Golimumab asis, and rheumatoid ar- available in the market of (Somponi) in April 2009 13. thritis. These agents have US. The first TNFa blocker been used successfully in that approved in August DRUG REVIEWS OF ANTI-TNF α In the early stages of Inflixima- which no response to in- Nonetheless, most authors of review studies empha- b's clinical use, discontinuation duction therapy. sise the importance of developing a reliable as- was reported to result in a loss Furthermore, up to half of say, particularly for meas- uring antidrug antibodies of response. This primarily patients who respond to and establishing cutoff levels to aid in decision- affected patients who received induction therapy with making 12. long-term treatment and then infliximab or adalimumab stopped using it 12. lose the effect and experi- One-third of patients who re- ence disease flares during ceive these biologics experi- ongoing maintenance ence primary treatment failure therapy 14,15.

Page 6 DRUG REVIEW HOSPITAL MELAKA PHARMACY NEWSLETTER Table 2 compares between Injection Infliximab and Injection Adalimumab Drug Infliximab 100mg Injection 16,17 Adalimumab 40mg Injection 16,18 I. Rheumatoid arthritis (moderate to severe), in combi- I. Third line treatment of: - Severe rheumatoid arthritis - Psoriatic arthritis - nation with methotrexate Ankylosing spondylitis after failure of conventional DMARDs or other biologics II. Ankylosing spondylitis in patients with active dis- II. Treatment of adults with moderate to severe chronic plaque psoriasis who ease despite treatment with methotrexate have not responded to, have contraindication or are unable to tolerate photo- FUKKM III. III. therapy and/or systemic therapies including acitretin, methotreaxate and Approved IV. Crohn's Disease in patients who have an inadequate IV. cyclosporine indication V. response to conventional therapies. V. Crohn's Disease Fistulizing Crohn's Disease in patients who have an inadequate response to conventional therapies For treatment of moderately to severely active Crohn's Disease in adult pa- tients who have inadequate response to conventional therapy Ulcerative Colitis in patients who have an inadequate response to conventional therapies For treatment of moderately to severely active Crohn’s Disease in adult pa- tients who have lost response to or are intolerant to infliximab VI. Ulcerative Colitis - For treatment of moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies Dosing I. Rheumatoid arthritis: ADULT over 18 years old: 3 III. Severe rheumatoid arthritis, Psoriatic arthritis, Ankylosing spondylitis : Subcu- mg/kg at 0, 2, 6 weeks, then every 8 weeks; May taneous 40 mg every other week increase to 10 mg/kg or increase dosing frequency to IV. Chronic plaque psoriasis : Initial, 80 mg SC, followed by 40 mg SC every other 4 weekly for patients with incomplete response. week starting one week after the initial dose Discontinue if no response by 12 weeks of initial infusion or after dose adjustment ii) Ankylosing V. Crohn's disease & Ulcerative colitis: 160mg at week 0 (dose can be adminis- spondylitis: ADULT over 18 years: 5 mg/kg IV over 2 tered as four injections in one day or as two injections per day for two consec- hour given at week 0, 2, and 6 then every 6-8 weeks. utive days) and 80mg at week 2. After induction treatment, the recommend- Discontinue if no response by 6 weeks of initial infu- ed maintenance dose is 40mg every other week via subcutaneous injection. sion. Half-life II. 5 mg/kg given as an intravenous infusion over a 2- 10 to 20 days hour period followed by additional 5 mg/kg infusion doses at 2 and 6 weeks after the first infusion, then every 8 weeks thereafter 7 to 12days Time to Unknown 131 ± 56hours peak 3 to 4 months Onset of CD: 1 to 2 weeks; action RA: 3 to 7 days; Injection site pain (12-20%) Development of antinuclear antibodies (50%) Upper respiratory tract infection (URTI) (17%) Common Infection (36%) side effect Upper respiratory tract infection (32%) Increased creatine phosphokinase (15%) Abdominal pain (12%; 26% with Crohn disease) Headache (12%) Nausea (21%) Rash (12%) Infusion-related reaction (20%) Sinusitis (11%) Headache (18%)

Page 7 DISEASE UPDATE HOSPITAL MELAKA PHARMACY NEWSLETTER Esophageal Disease Updated American College of Gastroenterology guidelines on gastroesophageal reflux disease (GERD) recommend19: 1.An empiric eight-week trial of proton pump inhibitors (PPI) in patients with classic GERD symptoms without alarm features. 2.Suggest a diagnostic endoscopy for those who do not respond adequately. 3.Attempts at discontinuation of PPIs after eight weeks in asymptomatic patients without Barrett's esophagus or erosive esophagitis. EMPIRICAL THERAPY WITH PPI FOR 8 WEEKS Patients with classic GERD symptoms of heartburn and regurgitation who have no severe symptoms: 1.It is recommended for an 8-week trial of empiric PPIs once daily pre meal (strong recommendation, moderate level of evidence). 2.To stop the PPIs in patients whose classic GERD symptoms respond to an 8-week empiric trial of PPIs (conditional recommendation, low level of evidence). ENDOSCOPY DISCONTINUATION OF PPI The guideline also suggests diagnostic endoscopy, ideally after PPIs Despite short-term use of PPIs is generally safe, long-term PPI therapies are stopped for 2–4 weeks, in patients whose classic GERD may be associated with adverse effects, such as fracture and C difficile symptoms do not respond adequately to 8-weeks empiric trial of infection. PPIs causes higher bacterial migration from the oral cavity to the PPIs or whose symptoms return when PPIs are discontinued intestinal lumen and increase colonic permeability, consequently impact (strong recommendation, low level of evidence). on the microbial population in the lower gastrointestinal tract. It has been reported that the gut microbiomes in PPI users and patients with IBD have Patients who have chest pain without heartburn and who have had certain characteristics in common, such as decreased diversity and adequate evaluation to exclude heart disease, an objective testing abundance of Faecalibacterium, and increased potentially pathogenic for GERD (endoscopy and/or reflux monitoring) is recommended species (eg, E coli and C difficile), suggesting PPI use may associate with (conditional recommendation, low level of evidence). IBD. Recommend endoscopy as the first test for evaluation of patients presenting with dysphagia or other alarm symptom and for patients with multiple risk factors for Barrett's esophagus (strong recommendation, low level of evidence). In patients for whom the diagnosis of GERD is suspected but not clear, and endoscopy shows no objective evidence of GERD, we recommend reflux monitoring be performed off therapy to establish the diagnosis (strong recommendation, low level of evidence).

Page 8 DISEASE UPDATE HOSPITAL MELAKA PHARMACY NEWSLETTER Gastric FECAL INCONTINENCE Disease WITH CONSTIPATION Updated American College of Gastroenterology guidelines on the management of fecal incontinence (FI) emphasize: 20 1.Recognizing the underlying causes. 2.Using anti-diarrheal medications for FI associated with diarrhea, using fiber and/or laxatives for FI associated with constipation, and biofeedback for patients who do not respond to initial measures. 3.Interventions such as injectable bulking agents, sacral nerve stimulation, and mechanical barrier devices are reserved for patients who do not respond to biofeedback. FECAL INCONTINENCE WITH DIARRHEA Laxative regimens sometimes benefit children and older patients with FI associated with constipation, but the Several drugs to manage diarrhea drugs (loperamide, diphenoxylate benefits in younger adults are not supported by objective (e.g., loperamide, diphenoxylate with plus atropine, and codeine). In 4 evidence. Biofeedback therapy for FI seeks to increase the atropine, bile salt binding agents trials, symptoms were better with strength and coordination of the external anal sphincter such as cholestyramine and active treatment compared with without contracting the abdominal wall muscles and to colesevelam, anticholinergic agents, placebo, with improved and/or improve rectal sensation where necessary. In those and clonidine) are available. A restored fecal continence, improved patients with hypersensitivity to rectal distention who Cochrane review identified 13 fecal urgency, more formed stools, cannot delay defecation, biofeedback seeks to reduce randomized studies with 473 and reduced use of pads. rectal sensation so that patients can postpone defecation participants. Nine trials included only until more stool fills the rectum. Hence, biofeedback for FI persons with FI related to liquid stool, should be tailored to the symptoms and specific and 7 tested antidiarrheal anorectal dysfunctions. Indeed, among patients who did not adequately respond to medications, education, and behavioral therapy, 76% of patients treated with biofeedback versus 41% with pelvic floor exercises alone reported adequate relief at 3 months. In summary, biofeedback therapy benefits many patients and does not cause harm. Hence, biofeedback is regarded by many as a mainstay of treatment for FI. INJECTABLE BULKING AGENTS Injectable bulking agents, which are used to augment the urethral sphincter and treat urinary incontinence, were approved by the US Food and Drug Administration for managing FI. In a multicenter, placebo-controlled randomized trial of a perianal bulking agent (dextranomer in stabilized hyaluronic acid [NASHA Dx]) in 206 patients with FI, >50% reduction in incontinence episodes was reported more frequently for NASHA Dx (52% patients) than placebo (31% patients). A prospective multicenter trial in 136 FI patients found that fecal continence improved in 52% of patients in 6 months, and this was sustained after 36 months.

Page 9 NEW DRUG PROFILE HOSPITAL MELAKA PHARMACY NEWSLETTER BUDESONIDE MMX TABLET C O R T I M E N T 9 M G P R O L O N G E D R E L E A S E D T A B L E T 21 Indication22 Induction of remission in active microscopic colitis (MC) Dose21,22,24 Budesonide MMX 9 mg daily for 8 weeks Mechanism High topical anti-inflammatory activity on the intestine. Budesonide of action 21-23 depresses the inflammatory activity of endogenous chemical mediators such Release as kinins and prostaglandins, inhibits protein synthesis and transcription, mechanism 21,22 and decreases the production of inflammatory cytokines. Pharmaco - The gastric acid-resistant coating of the Multi-matrix (MMX) formulation kinetic21,22,25 gradually dissolves in the intestine (where pH ≥7), enabling a controlled and Side Effects21,22 extended release of budesonide throughout the ascending, transverse, and descending colon. Special Consideration 21,22 A: Low bioavailability (~10%), due to extensive first-pass metabolism by the liver. D: Volume of distribution around 3 L/kg, plasma protein binding 85–90%. M: Approximately 90% undergoes first-pass metabolism via CYP3A4 into inactive metabolites: 16-a-hydroxyprednisolone and 6-b-hydroxybudesonide. E: Rate of elimination is limited by absorption. Excreted as metabolites, in urine (60%), and feces. Common: · Insomnia, headache, nausea. · Abdominal pain, abdominal distension, dry mouth, dyspepsia. · Acne, myalgia, fatigue · Decreased blood cortisol Uncommon: · Influenza, leukocytosis, altered mood, dizziness, flatulence. Conditions that may lead to increase in bioavailability of oral budesonide and a higher risk of systemic glucocorticoid adverse effects: · Concurrent use of moderate and strong CYP3A4 inhibitors such as ketoconazole or grapefruit juice. · Liver Cirrhosis.

Page 10 PHARMACY HOSPITAL MELAKA PHARMACY NEWSLETTER EDUCATION BOWEL PREP26,27 Brand Pico-Salax® VS Fortrans® VS Oral Fleet® Composition Sodium Picosulfate, Polyethylene Glycol / Macrogol Monobasic Sodium 4000 Powder Magnesium Oxide & Citric Acid Phosphate 48%, Dibasic Powder for Oral Solution Sodium Phosphate 18% Cost RM 28.38/2 sachets RM52.50/4 sachets RM11.14/bottle 2 sachets per treatment 3 sachets/treatment 2 bottles/treatment Onset Within 3 - 6 hours or less Within 1 - 2 hours Within 0.5 - 6 hours 150mL/sachet 1L/sachet 240 mL/bottle Dilution Dosing First dose on the evening before Early morning procedure - First dose taken Morning appointment - The day before the day of procedure. regimen Second dose in the morning prior at 4 pm, second dose at 6 pm, and third examination, first dose taken at 7 am and second dose taken at 7 pm. to the procedure. dose at 8 pm, one day before procedure. Afternoon appointment - First dose Afternoon (or later) procedure - First dose taken the day before examination at 7 taken at 6 pm, second dose at 8 pm, one pm while second dose taken on the day before procedure and third dose at 6 study day am on the day of procedure. Hyponatraemia, epilepsy, grand mal Nausea, abdominal pain and abdominal Dizziness, headache, nausea, distension (bloating), vomiting, severe abdominal pain, abdominal allergic reaction involving swelling of the face, lips, tongue, or throat, or breathing distension, diarrhea, vomiting, tremor, difficulties (anaphylactic shock), hives, body weakness, chest pain and Side effects allergic reaction MAIN ARTcIoCnvEuLlsions,nausea, rash, headache, Assess serum electrolytes and anaphylactoid reaction, renal function in patients at “THE GLOBAL EDUCATIONhypersensitivity higher risk of product-related CHALLENGES” rash, itchy skin (pruritus). adverse events. Serum electrolytes and renal BY MR.fHunOctiWon AteRstDs inOpaNtiGent,sTwHithEoPr aRtINCIPBAULN, creatinine, electrolytes, Monitoring risk for renal impairment or serum glucose, urine osmolality seizure and in patients who have a and ECG. history of electrolyte abnormality. Restrictions CKD Stage 1 - 3 (IHD & CKD) CKD Stage 4 - 5

Page 11 ACTIVITIES HOSPITAL MELAKA PHARMACY NEWSLETTER Kursus Farmakoterapi 2022 : Gastroenterology Venue: Google Meet / Hepatology Date: 26 March 2022 Time: 8.00 a.m. - 5.00 p.m. Objectives: 1. Empowering knowledge of pharmacists based on the latest guidelines on drug indications involved in the discipline of gastroenterology and hepatology. 2. To expose pharmacists to pharmacotherapy, monitoring of side effects and management of side effects that can be used during patient counseling. 3. Fostering the spirit of continuous learning among pharmacists. Antibiotic Updates 2022 Venue: Google Meet and Zamrud room Date: 11 June 2022 Time: 8.00 a.m. - 4.00 p.m. Objectives: 1.To increase the knowledge of antibiotics among pharmacists in Hospital Melaka so that antibiotics can be used rationally therefore to avoid antimicrobial resistance. 2.Provide an updated information on effective antibiotic doses and the need for pharmacists to be more aware on the latest guidelines, and this knowledge may be used during the monitoring and management of patients. 3.To produce a responsible pharmacists on the use of antibiotics and indirectly optimize treatment to patients.

Page 12 ACTIVITIES HOSPITAL MELAKA PHARMACY NEWSLETTER Kursus Penggunaan Ubat Secara Berkualiti untuk Anggota Kesihatan Venue: Bilik Seminar Jabatan Forensik, Hospital Melaka Date: 15 Jun 2022 Time: 8.00 a.m. - 5.00 p.m. Objectives: 1. Educate consumers in particular health care professional on the rational and correct ways of using medications. 2.Empowering the quality use of medications among health care professional. 3.To promote a proper drug use among health care personnel and the community.

Page 13 MISCELLANEOUS HOSPITAL MELAKA PHARMACY NEWSLETTER REFERENCES NEW STAFFS 1.Inflammatory bowel disease (IBD) [Internet]. AGA GI Patient Center. 2022 [cited 19 March 2022]. Available from: https://patient.gastro.org/inflammatory-bowel-disease-ibd/ 2.Surgical Algorithm for Inflammatory Bowel Disease 2019. Malaysian Society of Colorectal Surgeons. Available from: http://www.colorectalmy.org/downloads/IBD_Surgical_Algorithm.pdf 3.Overview of the medical management of mild (low risk) Crohn disease in adults [Internet]. Uptodate.com. 2022 [cited 19 March 2022]. Available from: https://www.uptodate.com/contents/overview-of-the-medical-management-of-mild- low-risk-crohn-disease-in-adults# 4.Harvey RF, Bradshaw JM. A simple index of Crohn's-disease activity. Lancet 1980; 315 (8167): 514. 5.Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease [Internet]. Uptodate.com. 2022 [cited 20 March 2022]. Available from: https://www.uptodate.com/contents/overview-of-medical- management-of-high-risk-adult-patients-with-moderate-to-severe-crohn-disease Noraini binti Saari 6.Center for Drug Evaluation and Research. Warnings about infection with legionella and listeria bacteria [Internet]. U.S. Food and Drug Administration. FDA; [cited 2022Mar18]. Available from: https://www.fda.gov/drugs/drug-safety-and- availability/fda-drug-safety-communication-drug-labels-tumor-necrosis-factor-alpha-tnfa-blockers-now- PEGAWAI FARMASI UF54 include#:~:text=The%20pathogens%20Legionella%20and%20Listeria,patients%20treated%20with%20TNF%CE%B 1%20blockers. 7.UpToDate. [cited 2022Mar18]. Available from: https://www.uptodate.com/contents/classic-kaposi-sarcoma-clinical- features-staging-diagnosis-and-treatment#H1 8.Tumour necrosis factor alpha (TNFΑ): Kaposi's sarcoma [Internet]. National Pharmaceutical Regulatory Agency (NPRA). 2021 [cited 2022Mar18]. Available from: https://www.npra.gov.my/index.php/en/health-professionals/recent- updates/426-english/safety-alerts-main/safety-alerts-2021/1527184-tumour-necrosis-factor-alpha-tnf-kaposi-s- sarcoma.html 9.European Medicines Agency (EMA). PRAC recommendations on signals. 2020 August 3 [Cited 2022 March 18]. EMA/PRAC/367621/2020 10.National Pharmaceutical Regulatory Agency. The Malaysian National ADR Database [Internet]. 2020 [Cited 2022 March 18]. Available from: https://www.npra.gov.my 11.Hu S, Liang S, Guo H, Zhang D, Li H, Wang X, et al. Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor α-associated diseases from a molecular view. Journal of Biological Chemistry. 2013;288(38):27059–67. 12.Silva-Ferreira F, Afonso J, Pinto-Lopes P, Magro F. A systematic review on infliximab and Adalimumab Drug Monitoring. Inflammatory Bowel Diseases. 2016;22(9):2289–301. 13.Center for Drug Evaluation and Research. Warnings about infection with legionella and listeria bacteria [Internet]. U.S. Nurfarah Aileen binti Mihat Food and Drug Administration. FDA; [cited 2022Mar18]. Available from: https://www.fda.gov/drugs/drug-safety-and- PENOLONG PEGAWAI availability/fda-drug-safety-communication-drug-labels-tumor-necrosis-factor-alpha-tnfa-blockers-now- FARMASI U29 include#:~:text=The%20pathogens%20Legionella%20and%20Listeria,patients%20treated%20with%20TNF%CE%B 1%20blockers. 14.Allez M, Karmiris K, Louis E, et al. Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects. J Crohns Colitis. 2010;4:355–366. 15.Ford AC, Sandborn WJ, Khan KJ, et al. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011;106:644–659. 16.Pharmaceutical Services Programme, Ministry of Health Malaysia. Formulari Ubat KKM (FUKKM). [Internet]. 2022 [Cited 2022 March 18]. Available from: https://www.pharmacy.gov.my/v2/en/apps/fukkm? generic=&category=&indications 17. https://www.uptodate.com/contents/infliximab-including-biosimilars-drug-information search=infliximab&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&dis play_rank=1 18. https://www.uptodate.com/contents/adalimumab-including-biosimilars-drug-information? search=adalimumab&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general& display_rank=1 19.ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux 2021 20.The American College of Gastroenterology 2021. 21.Uptodate. 2022. Oral budesonide formulations used in treatment of inflammatory bowel disease. (SmPC) - Muhammad Fadzli Shah bin 22.Medicines.org.uk. 2020. Cortiment 9 mg, prolonged release tablets - Summary of Product Characteristics (emc). [online] Available at: <https://www.medicines.org.uk/emc/product/1895/smpc#gref>. Zulkafli 23.QUEST 3+. 2021. Cortiment Consumer Medication Information Leaflet. [online] Available at: <https://quest3plus.bpfk.gov.my/front- PEMBANTU PERAWATAN end/attachment/34793/pharma/242606/V_52452_20210715_105200_D4.pdf>. KESIHATAN U11 24.Shor J, Churrango G, Hosseini N, Marshall C. Management of microscopic colitis: challenges and solutions. Clin Exp Gastroenterol. 2019;12:111-120. Published 2019 Feb 27. doi:10.2147/CEG.S165047 25.Uptodate. 2022. Budesonide (systemic): Drug information. 26.Product Insert of Pico-salax, Fortrans, Oral fleet. 27.Connor A, Tolan D, Hughes S, Carr N, Tomson C. Consensus guidelines for the safe prescription and administration of oral bowel-cleansing agents. Gut. 2012 Nov;61(11):1525-32. EDITORIAL TEAM Advisor: Editor: Puan Siti Hir Huraizah Md Tahir Nur Anis Sahira binti Abd Rahman Editorial Board: Contributors: Lim Chia Wei Wong Zhi Chin Umi Solehah binti Sa'ad Lyana Tan Mei Choo Chong Lai Peng Lee Kwang Yau Low Khai Hang Uma Shangkari Pattu A/P Ramani Nor Hafizah binti Dolah

FOR MORE INFORMATION OR DRUG ENQUIRIES, PLEASE CONTACT: PHARMACY AND INFORMATION RESOURCES CENTRE (PRIC), DEPARTMENT OF PHARMACY, HOSPITAL MELAKA EXT 2583 MONDAY - FRIDAY (8 A.M.— 5 P.M.) CONTACT