SAFETY OF TOPICAL NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) USING THE THAI HEALTH PRODUCT VIGILANCE CENTER DATABASE

  • Naruemon Bamrungsawad Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
  • Nilawan Upakdee Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
  • Chuenjid Kongkaew Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
  • Anjana Fuangchan Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok
  • Pakawadee Sriphiromya Rural and Local Consumer Health Products Promotion Protection Division, Food and Drug Administration, Ministry of Public Health, Nonthaburi
Keywords: topical non-steroidal anti-inflammatory drugs (NSAIDs), adverse events, Thai Vigibase

Abstract

This study sought to determine the characteristics of adverse events (AEs) reported in patients using topical non-steroidal anti-inflammatory drugs (NSAIDs) in Thailand as per the Thai Health Product Vigilance Center Database (Thai Vigibase). All AE reports from 1984 to 2016, involving topical NSAIDs and registered in Thailand, were retrieved from the Thai Vigibase. The following information on patient demographics was extracted from each report: age, gender, history of drug allergy, concomitant diseases, suspected drugs, timing of drug exposure, concomitant drugs, suspected reactions, time to onset of AEs, seriousness, and causality assessment. Descriptive statistics were used for data analyses. Results identified 179 AEs as reported by hospitals. The mean age was 47.2±17.2 years and 56.4% were female. Diclofenac (49.2%), ketoprofen (25.4%), and piroxicam (21.5%) were the three most commonly suspected drugs. Eighteen AE reports (10.1%) were classified as serious with 14 cases (7.8%) requiring hospitalization or prolonged hospitalization, and 2 cases (1.1%) resulted in death related to toxic epidermal necrolysis (TEN) and eczema. Of the 179 total reports, 249 AEs were found. Overall, skin and appendage disorders were the most common AEs reported (77.1%), followed by the body as whole - general disorders (8.8%), application site disorders (6.8%), gastrointestinal system disorders (2.4%), and disorders of the central and peripheral nervous system (1.6%). Most AEs (88.9%) occurred during the first week of treatment, of which 39.2% manifested within 24 hours after application. The causality of most reported events was classified as probable (57.5%). The most frequent skin AEs were pruritus and rash. In conclusion, topical NSAIDs were potentially associated with a risk of skin AEs. However, systemic AEs were uncommon. Further studies are needed to investigate the safety of topical NSAIDs for long-time use and in patients with severe or unstable comorbidities.

Downloads

Download data is not yet available.

References

Aronoff GM. Medication management of chronic pain: what you need to know. Bloomington (IN): Trafford Publishing; 2017.

Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheumatol. 2020;72(2):220-33.

Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27:1578-89.

Bruyere O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019;49:337-50.

Rafanan BS, Jr., Valdecanas BF, Lim BP, Malairungsakul A, Tassanawipas W, Shiyi C, et al. Consensus recommendations for managing osteoarthritic pain with topical NSAIDs in Asia-Pacific. Pain Manag. 2018;8(2):115-28.

Derry S, Conaghan P, Da Silva JA, Wiffen PJ, Moore RA. Topical NSAIDs for chronic musculoskeletal pain in adults: Cochrane Database Syst Rev [Internet]. 2016 [cited 2020 Jun 28]. Available from: https://www.cochranelibrary.com/cdsr/ doi/10.1002/14651858.CD007400.pub3/full

Derry S, Moore RA, Gaskell H, McIntyre M, Wiffen PJ. Topical NSAIDs for acute musculoskeletal pain in adults: Cochrane Database Syst Rev [Internet]. 2015 [cited 2020 Jun 28]. Available from: https://www.cochranelibrary.com/cdsr/ doi/10.1002/14651858.CD007402.pub3/full

Makris UE, Kohler MJ, Fraenkel L. Adverse effects of topical nonsteroidal antiinflammatory drugs in older adults with osteoarthritis: a systematic literature review. J Rheumatol. 2010;37(6):1236-43.

Honvo G, Leclercq V, Geerinck A, Thomas T, Veronese N, Charles A, et al. Safety of Topical non-steroidal anti-inflammatory drugs in osteoarthritis: outcomes of a systematic review and meta-analysis. Drugs Aging. 2019;36 Suppl 1:S45-64.

Berlin JA, Glasser SC, Ellenberg SS. Adverse event detection in drug development: recommendations and obligations beyond phase 3. Am J Public Health. 2008;98(8):1366-71.

Haroutiunian S, Drennan DA, Lipman AG. Topical NSAID therapy for musculoskeletal pain. Pain Med. 2010;11:535-49.

Durbize E, Vigan M, Puzenat E, Girardin P, Adessi B, Desprez PH, et al. Spectrum of cross-photosensitization in 18 consecutive patients with contact photoallergy to ketoprofen: associated photoallergies to non-benzophenone-containing molecules. Contact Dermatitis. 2003;48:144-9.

Hindsen M, Zimerson E, Bruze M. Photoallergic contact dermatitis from ketoprofen in southern Sweden. Contact Dermatitis. 2006;54:150-7.

Durieu C, Marguery MC, Giordano-Labadie F, Journe F, Loche F, Bazex J. [Photoaggravated contact allergy and contact photoallergy caused by ketoprofen: 19 cases]. Ann Dermatol Venereol. 2001;128(10 Pt 1):1020-4.

Flapan D. Topical diclofenac labeling updated to match oral agents' hepatotoxicity warnings [Internet]. Atlanta (GA): WebMD LLC; c2009 [updated 2009 Dec 18; cited 2019 Oct 10]. Available from: http://www.medscape.com/viewarticle/713451

Daniels AM, Gibbs LM, Herndon CM. Elevated transaminases with topical diclofenac: a case report. J Pain Palliat Care Pharmacother. 2018;32(2-3):161-4.

Yerly G, Cereda JM. Severe hepatitis due to percutaneous diclofenac. Gastroenterol Clin Biol. 2008;32:824-5.

Food and Drug Administration. Health Product Vigilance Center. Health product vigilance system in Thailand: for improving the safety of medicines and other health products in Thailand. Nonthaburi: FDA; 2016. (in Thai)

Food and Drug Administration. Health Product Vigilance Center. Annual Report 2019: health product vigilance [Internet]. Nonthaburi: FDA; 2019 [cited 2020 Apr 16]. Available from: http://thaihpvc.fda.moph.go.th/thaihvc/Public/News/uploads/hpvc_3_23_0_100947.pdf (in Thai)

Saokaew S, Suwankesawong W, Permsuwan U, Chaiyakunapruk N. Safety of herbal products in Thailand: an analysis of reports in the thai health product vigilance center database from 2000 to 2008. Drug Saf. 2011;34(4):339-50.

Boonmuang P, Nathisuwan S, Chaiyakunapruk N, Suwankesawong W, Pokhagul P, Teerawattanapong N, et al. Characterization of statin-associated myopathy case reports in Thailand using the health product vigilance center database. Drug Saf. 2013;36(9):779-87.

Suwankesawong W, Saokaew S, Permsuwan U, Chaiyakunapruk N. Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database. BMC Complement Altern Med. 2014;14:515.

U.S. Food and Drug Administration. Guidance for industry on warnings and precautions, contraindications, and boxed warning sections of labeling for human prescription drug and biological products-content and format [Internet]. Washington (DC): Federal Register, National Archives; 2011 [updated 2011 Oct 12; cited 2019 Oct 10]. Available from: https://www.federalregister.gov/d/2011-26297

Ramdas D, Chakraborty A, Hs S, Faizan S, Kumar VP, Bn S. A study of package inserts in southern India. J Clin Diagn Res. 2013;7(11):2475-7.

Health Sciences Authority. Package insert amendments reflecting safety issues. ADR News [Internet]. 2010 [cited 2019 Oct 10];12(1):11. Available from: https://www.hsa.gov.sg/ announcements/adverse-drug-reaction-news-bulletin/2010-april-(volume-12-number-1)

Sriphiromya P, Theeraroungchaisri A. An analysis of legal warnings after drug approval in Thailand. Regul Toxicol Pharmacol. 2015;71:108-13.

Ministry of Public Health (Thailand). Notification of the Ministry of Public Health on medication lists required to provide information for the safe use on labeling and patient package insert (no.42) B.E. 2553 [Internet]. Nonthaburi: The Ministry; 2010 [updated 2010 Feb 2; cited 2019 Oct 10]. Available from: http://www.fda.moph.go.th/sites/drug/Shared%20Documents/Law03-TheMinistryOfHealth/law03-05-42.pdf (in Thai)

Ministry of Public Health (Thailand). Medicines Regulation Division. Statistic data [Internet]. Nonthaburi: The Division; 2020 [cited 2020 Apr 16]. Available from: http://www.fda.moph.go.th/sites/drug/SitePages/Statistic.aspx (in Thai)

Lindquist M. Documentation grading of ICSRs and improved data quality management in Vigibase. Drug Saf [Internet]. 2007 [cited 2020 Apr 16];30(10):919-90. Available from: https://link.springer.com/article/10.2165/00002018-200730100-00093 [Subscription required to view].

Lindquist M. VigiBase, the WHO global ICSR database system: basic facts. Drug Inf J. 2008;42:409-19.

Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-45.

Riedl MA, Casillas AM. Adverse drug reactions: types and treatment options. Am Fam Physician. 2003;68(9):1781-90.

Evans JM, McMahon AD, McGilchrist MM, White G, Murray FE, McDevitt DG, et al. Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study. BMJ. 1995;311(6996):22-6.

Baraf HS, Gold MS, Petruschke RA, Wieman MS. Tolerability of topical diclofenac sodium 1% gel for osteoarthritis in seniors and patients with comorbidities. Am J Geriatr Pharmacother. 2012;10(1):47-60.

Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, et al. Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy. 2013;68;1219-32.

Wöhrl S. NSAID hypersensitivity - recommendations for diagnostic work up and patient management. Allergo J Int. 2018;27(4):114-21.

Ministry of Public Health (Thailand). Notification of the Ministry of Public Health on medication lists required to provide information for the safe use on labeling and patient package insert (no.55) B.E. 2558 [Internet]. Nonthaburi: The Ministry; 2015 [updated 2015 Feb 2; cited 2019 Oct 10]. Available from: http://www.fda.moph.go.th/sites/drug/Shared%20Documents/Law03-TheMinistryOfHealth/law03-05-55.pdf (in Thai)

Published
2020-10-26
Section
Original Research Articles