Editing Doxycycline (section)

==History==
After [[penicillin]] revolutionized the treatment of bacterial infections in World War II, many chemical companies moved into the field of discovering antibiotics by [[bioprospecting]]. [[American Cyanamid]] was one of these, and in the late 1940s chemists there discovered [[chlortetracycline]], the first member of the [[tetracycline antibiotic|tetracycline class]] of antibiotics.<ref name="pmid22191524">{{cite journal | vauthors = Nelson ML, Levy SB | title = The history of the tetracyclines | journal = Annals of the New York Academy of Sciences | volume = 1241 | issue = 1 | pages = 17–32 | date = December 2011 | pmid = 22191524 | doi = 10.1111/j.1749-6632.2011.06354.x | s2cid = 34647314 | bibcode = 2011NYASA1241...17N }}</ref> Shortly thereafter, scientists at Pfizer discovered [[oxytetracycline]] and it was brought to market. Both compounds, like penicillin, were natural products and it was commonly believed that nature had perfected them, and further chemical changes could only degrade their effectiveness. Scientists at Pfizer led by [[Lloyd Conover]] modified these compounds, which led to the invention of [[tetracycline]] itself, the first semi-synthetic antibiotic. Charlie Stephens' group at Pfizer worked on further analogs and created one with greatly improved stability and pharmacological efficacy: doxycycline. It was clinically developed in the early 1960s and approved by the FDA in 1967.<ref name="pmid22191524"/>

As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and [[International Rectifier]]<ref name="Justia Law">{{cite web|url=https://law.justia.com/cases/federal/district-courts/FSupp/545/486/1432019/|archive-url=https://web.archive.org/web/20150224061035/http://law.justia.com/cases/federal/district-courts/FSupp/545/486/1432019/|url-status=dead|title=Pfizer, Inc. v. International Rectifier Corp., 545 F. Supp. 486 (C.D. Cal. 1980)|archive-date=24 February 2015|website=Justia Law}}</ref> that was not resolved until 1983; at the time it was the largest litigated patent case in US history.<ref name=LitigationEnd>{{cite web | agency = The Associated Press | date = 6 July 1983 | url = https://www.nytimes.com/1983/07/06/business/pfizer-to-get-rachelle-units.html | title = Pfizer to Get Rachelle Units | archive-url = https://web.archive.org/web/20160306165725/http://www.nytimes.com/1983/07/06/business/pfizer-to-get-rachelle-units.html | archive-date=6 March 2016 | work = The New York Times }}</ref> Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifier's subsidiary, Rachelle Laboratories.<ref name=LitigationEnd/>

In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues".<ref name="CDC Health Alert Network-2013">{{cite web | work = CDC Health Alert Network | date = 12 June 2013 | url = http://emergency.cdc.gov/han/han00349.asp | title = Nationwide Shortage of Doxycycline: Resources for Providers and Recommendations for Patient Care | archive-url = https://web.archive.org/web/20150215093954/http://emergency.cdc.gov/han/han00349.asp | archive-date=15 February 2015 }}</ref> Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, [[Teva Pharmaceutical Industries|Teva]] (which ceased production in May 2013), [[Mylan]], [[Actavis]], and [[Hikma Pharmaceuticals]].<ref name="American Society of Health-System Pharmacists.-2014">{{cite web | work = American Society of Health-System Pharmacists. | date = 12 December 2014 | url = http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=977 | title = Doxycycline Capsules and Tablets | archive-url = https://web.archive.org/web/20150101010923/http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=977 | archive-date=1 January 2015 }}</ref><ref name="American Society of Health-System Pharmacists.-2014-2">{{cite web | work = American Society of Health-System Pharmacists. | date = 12 November 2014 | url = http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=431 | title = Doxycycline Hyclate Injection | archive-url = https://web.archive.org/web/20150101011224/http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=431 | archive-date=1 January 2015 }}</ref> The shortage came at a particularly bad time, since there were also shortages of an alternative antibiotic, tetracycline, at the same time.<ref name="Consumer Reports News-2013">{{cite web | work = Consumer Reports News| date = 4 February 2013 | url = http://www.consumerreports.org/cro/news/2013/02/fda-reports-shortage-of-doxycycline-antibiotic-what-are-your-options/index.htm | title = FDA reports shortage of doxycycline antibiotic. What are your options? | archive-url = https://web.archive.org/web/20150101012412/http://www.consumerreports.org/cro/news/2013/02/fda-reports-shortage-of-doxycycline-antibiotic-what-are-your-options/index.htm | archive-date=1 January 2015 }}</ref> The market price for doxycycline dramatically increased in the United States in 2013 and early 2014 (from $20 to over $1800 for a bottle of 500 tablets),<ref name="WSMV-TV-2013">{{cite web | url = http://www.wsmv.com/story/21616095/sudden-increase-in-cost-of-common-drug-concerns-many | title = Sudden increase in cost of common drug concerns many | archive-url = https://web.archive.org/web/20141231084623/http://www.wsmv.com/story/21616095/sudden-increase-in-cost-of-common-drug-concerns-many | archive-date=31 December 2014 | work = [[WSMV-TV]] | date = 12 March 2013 | vauthors = Frio A }}</ref><ref name="Rosenthal-2014">{{cite web | vauthors = Rosenthal E | url = https://www.nytimes.com/2014/10/08/business/officials-question-the-rising-costs-of-generic-drugs.html | title = Officials Question the Rising Costs of Generic Drugs | archive-url = https://web.archive.org/web/20170223043227/https://www.nytimes.com/2014/10/08/business/officials-question-the-rising-costs-of-generic-drugs.html | archive-date=23 February 2017 | work = [[The New York Times]] | date = 7 October 2014 }}</ref><ref name="Palmer-2014">{{cite web | vauthors = Palmer E | work = FiercePharmaManufacturing | date = 13 March 2014 | url = http://www.fiercepharmamanufacturing.com/story/hikma-hits-jackpot-doxycycline-shortage/2014-03-13 | title = Hikma hits the jackpot with doxycycline shortage | archive-url = https://web.archive.org/web/20150101012858/http://www.fiercepharmamanufacturing.com/story/hikma-hits-jackpot-doxycycline-shortage/2014-03-13 | archive-date=1 January 2015 }}</ref> before decreasing again.<ref name="Costco Drug Information">{{cite web|url=http://www.costco.com/Pharmacy/drug-results-details-price?storeId=10301&catalogId=10051&langId=-1&searchKeyword=Doxycycline&drugId=212&drugName=Doxycycline&drugSearch=headerDrugSearch&isPharmacy=true&encodedDrugName=Doxycycline|title=Costco Drug Information|access-date=31 July 2016|url-status=live|archive-url=https://web.archive.org/web/20160304053451/http://www.costco.com/Pharmacy/drug-results-details-price?storeId=10301&catalogId=10051&langId=-1&searchKeyword=Doxycycline&drugId=212&drugName=Doxycycline&drugSearch=headerDrugSearch&isPharmacy=true&encodedDrugName=Doxycycline|archive-date=4 March 2016}}</ref><ref name="GoodRx">{{cite web|url=http://www.goodrx.com/doxycycline-hyclate?drug-name=doxycycline+hyclate|title=Doxycycline Hyclate Prices and Doxycycline Hyclate Coupons|work=GoodRx|access-date=31 July 2016|url-status=live|archive-url=https://web.archive.org/web/20160728183159/http://www.goodrx.com/doxycycline-hyclate?drug-name=doxycycline+hyclate|archive-date=28 July 2016}}</ref>