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Prolonged use of hydroquinone has been associated with cancer risk and exogenous ochronosis. The CARES (The Coronavirus Aid, Relief, and Economic Security Act) Act of 2020\u00a0has instituted significant changes to hydroquinone containing OTC (over the counter) products, and consequently, many hydroquinone\u2010based OTC products had to be withdrawn from the market. Henceforth, products containing hydroquinone would need US Food and Drug Administration approval via new drug application pathways for commercialization. Alternative treatment options to hydroquinone in clinical practice are reviewed in this paper with regard to their safety and efficacy vis a vis hydroquinone. Also, new potential treatment options such as thiamidol,\n                    <jats:italic>Polypodium leucotomos<\/jats:italic>\n                    , and glutathione are discussed. The review shows that these alternative depigmenting agents can be rationally combined to achieve desired treatment goals in the management of hyperpigmentation.\n                  <\/jats:p>","DOI":"10.1111\/jocd.14746","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T10:25:49Z","timestamp":1641983149000},"page":"4133-4145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Hyperpigmentation: Looking beyond hydroquinone"],"prefix":"10.1111","volume":"21","author":[{"given":"Naseem Ahmad","family":"Charoo","sequence":"first","affiliation":[{"name":"Succor Pharma Solutions Dubai Science Park  Dubai United Arab Emirates"},{"name":"Cenric Compounding LLC Dubai Science Park  Dubai United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1590\/abd1806\u20104841.20142353"},{"issue":"5","key":"e_1_2_8_3_1","first-page":"401","article-title":"Hyperpigmentation: an overview of the common afflictions","volume":"16","author":"Cayce KA","year":"2004","journal-title":"Dermatol Nurs"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0365-05962013000100009"},{"key":"e_1_2_8_5_1","first-page":"95","article-title":"Melanocortin 1 receptor: structure, function, and regulation","volume":"7","author":"Horrell EMW","year":"2016","journal-title":"Front Genet"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cosmetics6040057"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep07995"},{"issue":"4","key":"e_1_2_8_8_1","first-page":"AB1","article-title":"Combination (hydroquinone 5%, tretinoin 0.1%, and hydrocortisone 1%) cream in treating facial hyperpigmentation; a retrospective patient satisfaction study","volume":"66","author":"Fleming J","year":"2012","journal-title":"J Am Acad Dermatol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2007.03351.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2007.02.020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000504596"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/009841098158863"},{"key":"e_1_2_8_13_1","unstructured":"King and Spalding2020.https:\/\/www.jdsupra.com\/legalnews\/congress\u2010enacts\u2010otc\u2010monograph\u2010reform\u201096907\/#_edn21. 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