Barriers to communication Job bag number: NP-EU-NAL-0057 Date of preparation: September 2017 05/09/17 © Shionogi Limited. 33 Kingsway. London WC2B 6UF, UK Registered in England and Wales No. 07945432.

OIC is the most common and bothersome adverse event affecting patients on long-term opioid treatment1 OIC is characterised by infrequent bowel movements and incomplete bowel evacuation, along with other GI symptoms including abdominal pain and bloating, straining and gastric reflux2 GI, gastrointestinal; OIC, opioid-induced constipation. *Experienced by ≥30% of patients.1 1. Bell TJ, et al. Pain Med 2009;10:35–42; 2. Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology 2016;150:1257-1261. 05/09/17 © Shionogi Limited. 33 Kingsway. London WC2B 6UF, UK Registered in England and Wales No. 07945432.

As a result of their OIC symptoms, patients also experience a significant psychosocial impact on their lives Patients have been reported to experience embarrassment, depression, low self-esteem, social isolation, anger and frustration.1–3 “I am on and off the toilet straining to go…I look pregnant all the time, so I am self- conscious all of the time.”6 Some patients would rather not take opioids and endure their original pain, than experience the distressing pain of OIC.3–5 “I am always conscious of not overdoing the pain meds… I always think about the constipation that might result, and so I will try to take the smallest dose possible or do without.”5 OIC, opioid-induced constipation. 1. Rauck RL Pain Pract 2017;17:329–35 2. Larkin PJ, et al. Palliat Med 2008;22:796–807 3. Panchal SJ, et al. Int J Clin Pract 2007;61:1181–7 4. Morlion B, et al. Clin Drug Investig 2015;35:1–11 5. Dhingra L, et al. Pal Med 2012;27:447–56 6. Epstein RS et al. Adv Ther 2017;34:726–31 05/09/17 © Shionogi Limited. 33 Kingsway. London WC2B 6UF, UK Registered in England and Wales No. 07945432.

Patients may struggle to communicate their symptoms due to their feelings towards OIC In an online survey of opioid-treated chronic pain patients (n=489), 70% were ashamed or embarrassed to talk to their HCP about OIC.1 Feelings of embarrassment, depression and social isolation are linked to the high prevalence of frustration and/or irritability experienced by patients.1 Some patients would rather suffer in silence than risk having to change or reduce their pain medication.2 HCP, healthcare provider; OIC, opioid-induced constipation. 1. Rauck RL, Pain Pract 2017;17:329–35 2. LoCasale RJ, et al. J Manag Care Spec Pharm 2016;22:236–45 Patients were asked “Do you have any of the following feelings due to OIC?” and chose all of their feelings that applied 05/09/17 © Shionogi Limited. 33 Kingsway. London WC2B 6UF, UK Registered in England and Wales No. 07945432.

Patients not discussing their symptoms can lead to a disconnect between patient experience and physician perception1,2 Physicians may not fully appreciate the:1 extent of OIC symptoms negative effects on pain management and quality of life limited effectiveness of laxatives Effective communication between patients and their physicians, while essential for optimal patient outcomes can be hindered by time constraints and a reluctance to discuss embarrassing topics1–4 OIC, opioid-induced constipation. 1. LoCasale RJ, et al. J Manag Care Spec Pharm 2016;22:236–45 2. Rauck RL, Pain Pract 2017;17:329–35 3. Camilleri M, et al. Neurogastroenterol Motil 2014;26:1386–95; 4. Nelson AD, Camilleri M. Ther Adv Chronic Dis. 2016 Mar;7:121–34 05/09/17 © Shionogi Limited. 33 Kingsway. London WC2B 6UF, UK Registered in England and Wales No. 07945432.

There are clinically available tools and assessments to help the diagnosis of OIC and facilitate conversations with patients1–4* Bristol stool form scale (BSFS): A visual aid designed to help determine stool frequency and categorise stools into seven categories3 Bowel function index (BFI) A patient-reported outcome tool that has a numerical scale measuring the mean of: (1) ease of defaecation, (2) feeling of incomplete bowel evacuation and (3) personal judgement of constipation1 Patient assessment of constipation quality of life (PACQL) A 12-item questionnaire which measures patients’ health-related quality of life in relation to their OIC and their response to OIC treatment4 Using brief, easy-to- administer questionnaires can help assess patients’ pain severity and other symptoms, including OIC1,2 In addition, patients may find it less embarrassing to write down symptoms, allowing them to be more specific on the impact of OIC on their daily lives3 1 2 3 OIC, opioid-induced constipation. *For use in both clinical trials and general clinical practice. 1. Nelson AD, Camilleri M. Ther Adv Chronic Dis. 2016 Mar;7:121–34 2. Gaertner, J et al. J Clin Gastroenterol 2015;49:9–16 3. Lewis SJ, Heaton KW. Scand J Gastroenterol 1997;32:920–24 4. Frank L et l. Scand J Gastroentrol 1999;34:870–7. 05/09/17 © Shionogi Limited. 33 Kingsway. London WC2B 6UF, UK Registered in England and Wales No. 07945432.