DOC-20240508-WA0001..pptx presentation about naproxen

This presentation is regarding naproxen.

1. Naproxen RA , OA, Spondylitis, Post operative and Musculoskeletal injuries 1  

2. Classification of NSAIDs ( Nonsteroidal anti-inflammatory drugs )

3. What is COX1 and COX2 ? Naproxen Naproxen

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5. Pharmacodynamic It has anti-inflammatory ,analgesic and antipyretic action

6. Cardiac Safe NSAID

7. Lancet 2013; 382: 769–79 Coxib and Diclofenac: Increased Major Vascular Events Ibuprofen: Increased major coronary events Naproxen: Less vascular risk than other NSAIDs Meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 person years) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years) Coxib and Diclofenac Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14–1·66; p=0·0009) or diclofenac (1·41, 1·12–1·78; p=0·0036), chiefly due to an increase in major coronary events (coxibs 1·76, 1·31–2·37; p=0·0001; diclofenac 1·70, 1·19–2·41; p=0·0032) Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00–2·49; p=0·0103) and diclofenac (1·65, 0·95–2·85, p=0·0187) Ibuprofen Significantly increased major coronary events (2·22, 1·10–4·48; p=0·0253) Naproxen Did not significantly increase major vascular events (0·93, 0·69–1·27) Vascular death was not increased by naproxen (1·08, 0·48–2·47, p=0·80) High-dose naproxen is associated with less vascular risk than other NSAIDs

8. 8 BMJ 2011; 342 (Published 11 January 2011) Naproxen seems to be the safest analgesic for patients with osteoarthritis in cardiovascular terms Among the seven NSAIDs analysed, naproxen seemed least harmful for cardiovascular safety 31 trials in 116 429 patients with more than 115 000 patient Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36) Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death Naproxen seems to be the safest analgesic for patients with osteoarthritis in cardiovascular terms Among the seven NSAIDs analysed, naproxen seemed least harmful for cardiovascular safety

9. Pharmacokinetics 9 T1/2 Naproxen 12–17 hours. Diclofenac 1–2 hours Aceclofenac 4 hours Ibuprofen 1.8–2.4 hours Mefenamic acid 2 hours Nimesulide 1.96 to 4.73 hours Aspirin 15–20 minutes Paracetamol 1.25–3 hours. Etodolac 6.4-8.4 hours Flurbiprofen 3.8 hours Ketoprofen 1.8 hours Fenoprofen 2.5 hours Indomethacin 4-5 hours Meloxicam 20 hours Piroxicam 57 hours Adopted from Rx information

10. Pharmacokinetics 10 Pharmacokinetics   Naproxen Naproxen sodium Reference Bioavailability 95% 95% US FDA approved prescription information. Peak plasma concentration 2–4 hours 1–2 hours Onset of action 1 hr 30 mins (US FDA monograph ), naproxen sodium begins to work within 15 minutes [Br.J. Clin. Pharmac. (1980), 10, 259-263]. Duration of action 12 hrs 12 hrs US FDA approved prescription information. Protein binding >99% >99% Metabolism Liver Liver Excretion Urine (95%) Urine (95%) Half life 12-17 hrs 12-17 hrs

11. Indications US FDA approved prescription information 11 Naproxen Naproxen sodium Inflammatory Diseases   Osteoarthritis, Rheumatoid Arthritis, or Ankylosing Spondylitis Osteoarthritis, Rheumatoid Arthritis, or Ankylosing Spondylitis Acute conditions Acute Tendinitis/Bursitis, Gout, dysmenorrhea Acute Tendinitis/Bursitis, Gout, dysmenorrhea Headache / Migraine Not preferred Preferred Fever Not approved Approved as OTC Recommendation   Naproxen sodium is preferred for management of acute painful conditions when prompt onset of pain relief is desired OTC Not approved (USA) Approved (USA) for fever and pain

12. Clinical overview Focus of Fever , Headache , Body ach Associated with Respiratory Infections 12

13. Naproxen in the management of osteoarthritis 13 Semin Arthritis Rheum.  2016 Feb;45(4 Suppl): S22-7.

14. Osteoarthritis 723 studies of all conservative therapies Naproxen ranked most effective among conservative treatments of KOA because of its relative safety and low cost 14 J Am Acad Orthop Surg. 2018 May 1;26(9):325-336.

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16. 16 J Am Acad Orthop Surg. 2018 May 1;26(9):325-336.

17. 17 Effect of nonsteroidal anti-inflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials Simon Tarp et al., Arthritis Rheum. 2012 Nov;64(11):3511-21

18. A systematic review and meta-analysis of naproxen for prevention heterotopic ossification after hip surgery 18 Ai-Hua Zhang et al., Medicine (Baltimore) . 2019 Apr;98(14):e14607.

19. Naproxen in Knee Osteoarthritis Clinical Studies 19

20. Mixed Treatment Comparisons for Nonsurgical Treatment of Knee Osteoarthritis: A Network Meta-analysis Conclusions: Naproxen ranked most effective among conservative treatments of KOA and should be considered when treating pain and function because of its relative safety and low cost J Am Acad Orthop Surg. 2018 May 1;26(9):325-336. 1

21. The five treatments with the highest probability of ranking 1 to 5 (1 being most effective) when evaluating pain reduction are IA corticosteroids, ibuprofen, IA PRP, naproxen, and celecoxib (Figure 3) 21 J Am Acad Orthop Surg. 2018 May 1;26(9):325-336.

22. Analgesic efficacy and safety of non-prescription doses of naproxen sodium in the management of moderate osteoarthritis of the knee or hip Conclusions: Non-prescription naproxen sodium is effective and well tolerated in patients of all ages for the acute therapy of underlying pain in patients with moderate osteoarthritis of the hip or knee. Curr Med Res Opin . 2018 Oct;34(10):1747-1753. 2

23. 2 identical Multicenter, randomized, double-blind, placebo-controlled, multidose, parallel-design studies, Patients aged > or = 25 years with OA were randomized to daily doses of naproxen sodium 660 mg, naproxen sodium 440 mg (patients > or = 65 years), ibuprofen 1200 mg, or placebo, for 7 days. Naproxen sodium (440/660 mg) significantly improved all 7 symptoms from baseline compared with placebo. Naproxen sodium (440/660 mg) and ibuprofen (1200 mg) effectively relieve pain in patients with mild to moderate OA of the knee. Naproxen sodium provided more effective pain relief for most variables compared with placebo , and for night pain compared with ibuprofen. Efficacy was combined with good safety and tolerability. J Rheumatol. 2004 Jul;31(7):1373-83. 3

24. For each of the different symptoms, naproxen sodium (440/660 mg) was significantly superior to placebo at improving symptoms from baseline (Figure 2A) Subgroup of elderly patients, sodium 440 mg was significantly superior to placebo in all symptoms apart from pain on weight-bearing. Although improvement in this symptom did not reach statistical significance (p = 0.064),there was greater improvement following treatment with naproxen sodium compared with placebo and ibuprofen . J Rheumatol. 2004 Jul;31(7):1373-83. .

25. 25 patients with knee OA received naproxen (500 mg), placebo, or no treatment in 3 separate sessions in a randomized manner Naproxen effectively reduces pain-related brain responses involving different regions and the attenuation is related to subjective pain changes. The Journal of Rheumatology November 2014, 41 (11) 2240-2248. 4

26. Naproxen for the treatment of gout arthritis Clinical Studies 26

27. Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care Conclusions: N aproxen was associated with fewer side effects, less analgesic use and slightly lower costs, suggesting that, in the absence of contraindications, naproxen should be used ahead of low-dose colchicine to treat gout flares in primary care. Roddy E, et al. Ann Rheum Dis 2020;79:276–284. 1

28. Multicentre trial of naproxen and phenylbutazone in acute gout Conclusions: B oth the drugs were equally effective with few and relatively mild side effects. Naproxen is a useful alternative agent for the treatment of acute gout. Annals of the Rheumatic Diseases, 1977, 36, 80-82 2

29. The Treatment of Acute Gout with Naproxen Conclusions: Naproxen, a new anti-inflammatory phenylalkanoic acid given in total doses of 2.4 to 4.5 Gm, was effective in the treatment of acute gout. No gastrointestinal or serious side effects were encountered. Scand J Rheumatol Suppl. 1973;2:69-71. 3

30. Table 1: Time of Entry into Study After Onset of Attack of Acute Gout and Results After Naproxen Treatment for the 20 Patients Studied 15 of the 20 patients with acute gout responded favorably to naproxen therapy (Table I) Scand J Rheumatol Suppl. 1973;2:69-71.

31. Acute dental pain 12 studies, 587 participants Naproxen sodium shows a stronger analgesic effect either at 2 h or 6 h, and its effect lasts to 24 h. 31 BMC Oral Health. 2020 Sep 18;20(1):259.

32. OTC safety 46 clinical trial (Dental pain, Cold, Arthritis, Dysmenorrhea, Headache, Fever, Myalgia) Treatment with naproxen sodium may be highly beneficial from a clinical and economical perspective and safe when adhering to labeled directions. 32 J Clin Pharmacol.   2001 Feb;41(2):127-38.

33. Naproxen in Post operative pain and inflammation Clinical Overview

34. Post -Op pain 10 studies with 996 participants Provided effective analgesia to adults with moderate to severe acute postoperative pain 34 Cochrane Database Syst Rev .  2009 Jan 21;2009(1):CD004234

35. Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled, single-dose trial 35 Curr Med Res Opin. 2019 Dec;35(12):2149-2158

36. Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery 36 Braz J Anesthesiol. 2016 Mar-Apr;66(2):151-6.

37. Oral naproxen but not oral paracetamol reduces the need for rescue analgesic after adenoidectomy in children 37 Acta Anaesthesiol Scand. 2007 Jul;51(6):726-30.

38. Ranked No. 1 Longest acting NSAID (15 hrs) Cardiac safe NSAID Textbook product Thank you 38