Panadol Medical Affairs Training 2023 PDF

Panadol Medical Affairs training September 2023 Topics PANADOL VARIANTS Panadol What makes Panadol Base Basics of Pain, variants...

Panadol Medical Affairs training September 2023 Topics PANADOL VARIANTS Panadol What makes Panadol Base Basics of Pain, variants Paracetamol its classification the most comparable Panadol Extra Panadol Extra with Key Claims & management efficacy suitable OTC ? Optizorb vs.NSAIDs Panadol Soluble Introduction to pain April 2022  What is pain? The International Association for the Study of Pain defines pain as: “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”1,2 Pain plays an important role in the Pain can Each of us normal functioning of Pain also be the is different our bodies and warns cannot be first step in how we us to stop any activity ignored1 toward perceive that may cause further recovery1 pain1 damage to it1 Pain is subjective in When you are in pain, nature. Patients will If you touch a very describe pain hot surface, the pain you are more likely to rest and allow an according to its ensures you pull intensity and other your hand away injury to heal subjective qualities3 quickly, to prevent further damage 4 1. IASP Task Force on Taxonomy. Classification of Chronic Pain. In: Merskey H, Bogduk N, editors. Second Edition ed. Seattle: IASP Press; 1994. 209–14; 2. Loeser JD, Treede RD. Pain 2008;137:473–477; 3. Coghill RC. Headache 2010;50(9):1531–1535. Different pains experienced by an individual in any typical year 2 Body and head pain represent a significant global burden affecting billions of people1 93% suffered from body pain in the last year 83% suffer at least once a month 72% suffer at least once a month 27% suffer everyday 5 2. GPI 2020 Global Report Findings 1. GPI 2018 Global Report Findings. Body pain remains the most common pain, dominant over head pain FREQUENCY SEVERITY 7 in 10 suffering 58% from body pain of those aged 45 and think that their over suffer from body pain is quite or pain very severe (last CAUSE OF PAIN Body pain body pain 74%) 2 in 10 of those DURATION Pain in muscles, who know the tendons, ligaments and For 6 in 10 DIAGNOSIS causes of their joints (e.g., back pain, suffering from body pain have neck pain, shoulder pain One third who have body pain, it lasts self-diagnosed (last and osteoarthritis) experienced body at least several body pain 17% pain don’t know or hours (last are not sure of what body pain 60%) caused it (last body pain 33%) 6 1. GPI 2020 Global Report Findings.  Impact of pain on different aspects of life Physiological impact Emotional impact Quality of life impact 65% can’t be happy when 8 in 10 sufferers globally say their Severity say their pain is quite or they experience in pain quality of life is impacted by pain very severe 75% 60% Are moody when they 83% said pain has a negative Frequency suffer from pain weekly impact on their day-to-day are in pain or more 61% 72% say their pain decreases are in pain for at least several 47% say their pain makes their quality of life Duration hours anxious 55% Only 22% 42% say pain negatively Agree their pain has impacts their self-esteem “No impact at all, I do not change my daily routine in any way” 7 1. GPI 2020 Global Report Findings. Global Pain Index 2023 Key highlights 8  Global Pain Index 2023 Key highlights o The 5th edition of the Pain Index o 18 participating markets across 5 continents (KSA, India, China, Malaysia, Australia, Poland, France, UK, Mexico, South Africa, USA, Italy, Brazil, Canada, Sweden, Spain, Colombia and Germany) o 18,500+ participants, 10,000+ hours of interviews o 1st ever HCP leg in 4 countries (USA, Germany, KSA, Australia) including 600+ Physicians, Pharmacists, Nurse practitioners and Pharmacist Assistants o 1st time looking at pain through the lens of inclusivity: this edition draws particular attention to marginalised groups, looking at how inclusivity barriers are disproportionally impacting people from those subgroups living with pain 9  Global Pain Index 2023 Four key areas of insight that shed light on the state of pain across the world The lonely experience of pain Pain remains a universal issue, with 91% of the global population studied having suffered pain this year. HPI 5 calculated an overall Pain Index of 5.92 (from 4.97 in 2014 to 5.94 in the previous 2019 edition). Greater detail shows that while the physical impact of pain has remained relatively stable over this decade, its emotional and life impact have grown by almost 25% and loneliness is not just concentrated in older consumers. Society is failing those in pain For every 10 individuals who experienced pain, 4 consider it a taboo. This figure rises to 5 in 10 when individuals are asked to consider whether pain is a “social stigma”. This is magnified in marginalised populations, where 6 in 10 individuals from the LGBTQ+ community, for example, feel stigmatised due to their pain. Driving change for greater health inclusivity The key barriers to health inclusivity also apply to pain: a majority of people experiencing pain believed that tackling the access challenges (72% of people in pain), empowering greater health literacy (57%) and enabling more empathy against bias and prejudice (68%) would influence their experience and management of pain, as well as the impact pain has on their lives. Towards greater inclusivity with empathy Along with tackling bias and prejudice to increase empathy, 66% of individuals discussed the need for either greater understanding of the pain itself, increased outward demonstrations of empathy or more empathetic treatment when in pain. 10  Treatment guidelines for pain The Adapted WHO Analgesic Ladder Moderate-to-severe pain Mild-to-moderate pain STEP 3 Mild pain Strong STEP 2 opioid: morphine, Weak opioid: oxycodone, STEP 1 codeine (and its hydromorphone, derivatives) methadone, OTC oxycodone fentanyl analgesic: combination or  OTC analgesic Panadol, NSAIDs, tramadol  adjuvant aspirin  OTC analgesic  adjuvant  adjuvant 11 NSAID, non-steroidal anti-inflammatory drug; OTC, over-the-counter; WHO, World Health Organization. 1. WHO. Pain relief ladder. Available at: http://www.who.int/cancer/palliative/painladder/en/ (accessed March 2016). ĐAU NHỨC LÀ VẤN ĐỀ THƯỜNG GẶP Ở HẦU HẾT NGƯỜI TRƯỞNG THÀNH Đau đầu và đau nhức cơ thể là vấn đề quan trọng và phổ biến trên toàn cầu. Trung bình mỗi năm, dân số thế giới ở độ tuổi trưởng thành gặp ít nhất 10 loại đau khác nhau. 93% 84% dân số thế giới dân số thế giới mắc đối diện với các chứng đau đầu cơn đau. Tài liệu tham khảo: GPI 20 20 Global Report Findings, 19 countries, n=19,000, Jan 20 20 Q2.And what type of pain do you experience and how often? (at leas t one a year )  Các hướng dẫn điều trị đau Thang giảm đau do WHO phê duyệt Đau vừa đến nặng Đau nhẹ đến vừa BẬC 3 Nhóm opioid tác dụng mạnh: Đau nhẹ BẬC 2 morphine, oxycodone, hydromorphone, Nhóm opioid tác methadone, fentanyl dụng nhẹ: codeine (và các dẫn xuất của  thuốc giảm đau OTC BẬC 1 thuốc) phối hợp  chất bổ trợ Thuốc giảm đau oxycodone, hoặc OTC: Panadol, NSAID, tramadol aspirin  thuốc giảm đau OTC  chất bổ trợ  chất bổ trợ NSAID: Thuốc chống viêm không steroid; OTC: Không kê đơn; WHO: Tổ chức Y tế Thế giới. 1. WHO. Pain relief ladder. Available at: http://www.who.int/cancer/palliative/painladder/en/ (accessed March 2016). 13 Mode of action Paracetamol  How do we feel pain?1-2 Nociceptors (pain receptors) can be triggered by 1 chemicals released into the body by injured cells e.g., prostaglandins. – Prostaglandins have several important roles within 1 the body. – Some cause pain and others cause inflammation, when they are released. – Some also have protective roles, such as protecting the lining of the stomach. 15 1 Mertens P, Blond S, David R, Rigoard P. Anatomy, physiology and neurobiology of the nociception: a focus on low back pain (part A). Neurochirurgie 201 5;6 1 Suppl 1:S2 2-34 2 Ricciotto E, Fi tzGerald GA. Arteriosc ler Thromb Vas c Biol 201 1;3 1:9 86-100 0. How do we feel pain?1-2 Following contact with a stimulus, pain messages are 2 transmitted from the point of sensation to the brain through nerves, which send a signal to the central nervous system. 2 – The relay of information usually involves several 1 neurons within the central nervous system. 16 1 M erte ns P, Bl ond S , Davi d R , R ig oard P. A nato my, phy si ol ogy an d neu robi ol ogy of the n ocicep tion : a focus on l ow ba ck p ain (pa rt A ). Neu rochi rur gi e 20 15; 61 S upp l 1: S 22-34 2 Riccio tto E, Fi tzGera ld GA. A rter ioscl er Th romb V asc B iol 20 11; 31 :98 6-10 00. How do we feel pain? 31-2 The brain receives the information for further 3 processing and action. Once the message is processed, the brain alerts the body to change what it is doing and prevent further damage. 2 – e.g., removing your finger from the sharp object 1 17 1 Mertens P, Blond S, D avid R , Ri goard P. Anatomy, physi ol ogy and neurobiology of the noc iception: a focus on low bac k pai n (part A). Neurochirurgie 2015; 61 Suppl 1: S22-34 2 Ri cci otto E, Fi tz Geral d GA. Arterioscl er Thromb Vasc Biol 2011;31:986-1000. COX-1: Produce prostaglandins that play protective roles in the stomach, kidney and vascular system COX-2: Produce prostaglandins involved in pain, fever and inflammation.2 COX-3 (a splice variant of COX-1): Thought to be expressed at higher levels in the brain and central nervous system Generally accepted that paracetamol inhibits the cyclooxygenase (COX) enzymes, which produce prostaglandins throughout the body1,2 COX-2&3 (major effect is primarily COX-2) - target of paracetamol in humans, although strong supporting evidence is currently lacking1,2 Analgesic and antipyretic effect, but no anti-inflammatory activity1,2 1 Ghanem CI et al. Pharmacol Res 2016; 109:119-131 2 Graham GG et al. Inflammopharmacol 2013;21:201-232 18 3 Engstrom RL et al. Neu ropharmacology 2013;7:1124-129.  Panadol: gastrointestinal safety1,2 Gastrointestinal tolerability has been the cornerstone of the safety messages regarding Panadol for many years Panadol has no warnings or precautions relating to gastrointestinal safety Panadol is generally considered to only be a weak inhibitor of synthesis of prostaglandins that protect the lining of the stomach from digestive acid attack, 1 which is a risk with NSAIDs Panadol is not associated with upper gastrointestinal bleeding 2 NSAID, non-steroidal anti-inflammatory drug. 1. Graham GG, Scott KF. Am J Ther 2005;12(1):46–55; 2. Lewis SC et al. Br J Clin Pharmacol 2002;54:320–326. 19  Paracetamol is the most suitable analgesic for elderly 1,2 Paracetamol inhibits COX2/3 Panadol Ibuprofen GI suitability ✓  Ibuprofen (and other NSAIDs) inhibit COX1 too. Fewer contraindications ✓  COX1: involved in platelet aggregation, regeneration Low drug-drug interactions ✓  of GI and renal mucosa Low number of potential side effects ✓  Low potential for interaction with aspirin ✓  Suitable for patients with hypertension/ ✓  high blood pressure Suitable for patients with cardiovascular/ ✓  heart conditions Suitable for long-term use ✓  Paracetamol has a better safety and tolerability profile. Paracetamol is suitable for use by 98% of adults – significantly more than ibuprofen or aspirin3. GI, gastrointestinal. 20 1. American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. Pain Med 2009;10:1062–1083. 2. Marcum ZA et al. Ann Longterm Care. 2010;18(9): 24–27. Panadol has unsurpassed suitability among OTC analgesic medicines 40 Panadol is suitable for use by 98% of adults – significantly contraindications, warnings % patients with labeled 35 more people than ibuprofen or aspirin 30 and precautions 25 23.1* 20 16.6** 15 10 5 1.9 0 *p90% được chuyển hóa 90-100% bài tiết protein huyết tương trong mô1,2 khả dụng sinh học2 trong gan3 từ nước tiểu trong 24h4,5,6 Phải mất tới 50-60 phút để Paracetamol đạt được tác dụng của nó để tập trung tối đa tại vị trí đau Tài liệu tham khảo: SUB-07811 1. GSK Data on file. Global Datasheet-Paracetamol-v7 GIẢM ĐAU 2. Paracetamol Pharmacokinetics. Available at https://sepia2.unil.ch/pharmacology/drugs/paracetamol/ Accessed February 2020 3. EMC. Paracetamol. Available at https://www.medicines.org.uk/emc/product/4199/smpc. Accessed March 2020 4. Saccomana SJ. Nursing 2019;14(5):10-17 5. Jackson CH, et al. Can Med Assoc J 1984; 131:25-37. 6. Bannwarth B, et al. J Rheumatol 2001;28(1):1824.  Panadol Extra and Extra optizorb (+ Caffeine) Indications and recommended dosing in adults and children aged ≥12 years1,2 Indications Relief of Treatment of mild-to-moderate pain: fever Respiratory Pain and fever Symptoms of colds Headache Muscle ache Sore throat Toothache tract infections after vaccination and flu: headache, incl. cold / flu fever, sore throat, muscular aches and pains, reduced Pain after dental Pain of Musculoskeletal alertness, Migraine Dysmenorrhoea procedures/ tooth Earache/otalgia pain osteoarthritis drowsiness extraction Recommended dosing regimen – The recommended dosing regimen of Panadol / caffeine is 500–1000 mg / 65–130 mg every 4–6 hours, up to a maximum of 4000 mg / 520 mg in 24 hours Age 6–11 yrs: 0.5–1 tablet, every 4–6 hours, 4x daily 39  Panadol Extra (Paracetamol 500 mg + caffeine 65 mg] Key claim: For extra relief for stronger pain Treats 10 types of symptoms Specific Indications Headache, migraine, backache, toothache, rheumatic pain and ⎻ Migraine dysmenorrhoea, and the relief of the symptoms of colds, influenza and sore ⎻ Tension type headache throat, fever. ⎻ Dysmenorrhoea Suitability Dual Active Strong Formula Fast and effective pain relief for ⎻ GI suitability, empty stomach for tough pain relief tough pain ⎻ Suitable for elderly Provides up to 37% more Provides 10% greater pain relief powerful pain relief than std Leaves body naturally than std paracetamol paracetamol* * Subject to local market approval; GI, gastrointestinal Panadol Toolkit Product-specific information 40  Panadol Extra with Optizorb (Paracetamol 500 mg + caffeine 65 mg + Optizorb] Key claim: Strong pain relief with speed of Optizorb technology Provide up to 37% more powerful Starts to work 15min faster than Start to work 2x faster than before pain relief vs std paracetamol before / Starts to work in as / start to work half the time tablets* little as 10min Delivers 3x more of its pain Gets in to get job done on tough Designed to be strong and fast but relieving power early** vs Panadol pain and then leaves gentle on stomach Extra naturally in 24hrs *Subject to local market approval. **First 30 min Panadol Toolkit Product-specific information 41  PANADOL EXTRA RELIEF TOUGH PAIN Panadol Extra provides up to 37% more powerful pain relief than standard paracetamol(1) Based on pooled relative potency estimate over the dose range of 500-1500mg. Includes post-partum, headache, and dental extraction pain studies With caffeine for fast and effective relief for tough pains(2) “Caffeine in dose >65mg is considered an analgesic adjuvant” Adjuvant potentiate the effect of analgesics for greater pain relief without having any pharmacological effect  CÔNG THỨC PARACETAMOL VÀ CAFFEINE GIẢM ĐAU HIỆU QUẢ Công thức kết hợp 500mg paracetamol và 65mg caffeine giúp giảm đau hiệu quả hơn tới 37% so với paracetamol thông thường12. Số Số lượng Ước tính Thuốc giảm đau người 95% CI P value nghiên hiệu quả bệnh cứu Paracetamol Paracetamol + thông 6 2.625 1.37 1.13-1.70 ≤0.05 Caffeine thường Caffeine với liều >65 mg được coi là một tá dược giảm đau* Chất bổ trợ làm tăng tác dụng của thuốc giảm đau để giảm đau nhiều hơn mà không có bất kỳ ảnh hưởng của dược lý. Tài liệu tham khảo: SUB07391 OPTIZORB NAME CAME FROM THE FUSION OF “OPTIMAL” AND “ABSORPTION” OPTI ZORB OPTIMAL ABSORPTION WHAT IS OPTIZORB TECHNOLOGY? ❖ A combination of: Alginic acid Calcium carbonate Other ingredients Hydrophilic properties draw On contact with stomach acids, Crospovidone, a well- fluid into the tablet, causing it releases small amounts of established super-disintegrant, to swell, thus helping it break carbon dioxide that acts greatly facilitates tablet apart faster together with crospovidone to disintegration break up the tablet Derived from brown seaweed Widely used in formulation and Widely used as an excipient at food science low levels Classified by the FDA as Used as active ingredient at GRAS1,2 higher levels, as in antacids ❖ These key ingredients increase the rate of tablet disintegration in the stomach, allowing paracetamol to achieve therapeutic levels more rapidly. 45 2 TIMES FASTER THAN PANADOL EXTRA 3 Panadol Extra with Optizorb reaches maximum therapeutic levels 2 times faster than Panadol Extra 3 46 2 times faster than Panadol Extra Panadol Extra with Optizorb reaches maximum therapeutic levels 2 times faster than Panadol Extra3 10 min (0.17hr) vs 22 min (0.37 hr) in fasted state; which is 12 minutes faster Time to therapeutic level (T4) (4 μg/mL) was: 22 min (0.36 hr) vs 44 min (0.73 hr) in semi-fed state, which is 22 mins faster T4 is time concentration greater than 4 μg/mL for paracetamol Panadol Extra with Optizorb also showed significantly shorter time to reach maximum drug concentration (Tmax) for both paracetamol and caffeine as compared to Panadol Extra in both the fasted and semi-fed states. These data indicate that Panadol Extra with Optizorb could potentially have similar overall analgesic efficacy to the current formulation, but with significantly faster onset. 47  CÔNG NGHỆ OPTIZORB LÀ GÌ? ❖Sự kết hợp giữa : Alginic acid Calcium carbonate Thành phần khác Tính háo nước hút các dịch vào Khi tiếp xúc với acid dạ dày, phóng Crospovidone, là một chất siêu rã đã trong viên nén, khiến viên phồng lên thích lượng nhỏ carbon dioxid - kết được kiểm chứng rõ ràng, hỗ trợ tốt và vỡ ra nhanh hơn hợp với crospovidone giúp làm vỡ cho sự tan rã của viên nén viên nén Được sử dụng phổ biến như một tá Xuất xứ từ rong biển nâu dược ở nồng độ thấp Được sử dụng phổ biến trong các công Được sử dụng như một hoạt chất chính thức thuốc và thực phẩm ở nồng độ cao, như một thuốc kháng Phân loại GRAS theo FDA 1,2 acid ❖ Những thành phần quan trọng này làm tăng độ tan rã của thuốc trong dạ dày, cho phép paracetamol đạt tới ngưỡng điều trị tối thiểu nhanh hơn.  NHANH HƠN GẤP 2 LẦN SO VỚI PARACETAMOL THÔNG THƯỜNG Công thức paracetamol kết hợp caffeine với công nghệ Optizorb đạt ngưỡng điều trị nhanh hơn x2 lần so với paracetamol thông thường Thời gian (giờ) Thời gian (giờ) Fasted State Semi-Fed State Điều kiện Công thức Công thức Công thức mới Sự khác biệt Giá trị P Công thức mới Sự khác biệt Giá trị P hiện tại hiện tại T4 0.17 0.37 -0.2