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{{Short description|Medication that decreases stomach acid}}
{{Drugbox
{{Use British English|date=September 2019}}
{{Use dmy dates|date=June 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 407851152
| verifiedrevid = 458460406
| IUPAC_name = ''N''-(2-ethyl)- ''N''-methyl- 2-nitroethene- 1,1-diamine
| image = Ranitidine Structural Formulae.png | image = Ranitidine.svg
| width = 200 | width = 250
| image2 = Ranitidine-A-3D-balls.png | alt =
| image2 = File:Ranitidine-A-3D-balls.png
| alt2 =
| JAN = ranitidine hydrochloride


<!--Clinical data--> <!-- Clinical data -->
| tradename = Zantac | pronounce =
| tradename = Zantac,<ref name="Zantac FDA label">{{cite web | title=Zantac 150 (ranitidine hydrochloride) Tablets, USP Zantac 300 (ranitidine hydrochloride) Tablets, USP | website=DailyMed | date=28 June 2018 | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=379425 | access-date=18 February 2021 | archive-date=4 July 2022 | archive-url=https://web.archive.org/web/20220704051405/https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=379425 | url-status=live }}</ref> others
| Drugs.com = {{drugs.com|monograph|ranitidine-hydrochloride}} | Drugs.com = {{drugs.com|monograph|ranitidine-hydrochloride}}
| MedlinePlus = a601106 | MedlinePlus = a601106
| licence_US = Ranitidine | DailyMedID = Ranitidine
| pregnancy_AU = B1 | pregnancy_AU = B1
| pregnancy_AU_comment = <ref name = RanitidinePregnancy>{{cite web | title = Ranitidine use during pregnancy | website = Drugs.com | date = 2 December 2019 | url = https://www.drugs.com/pregnancy/ranitidine.html | access-date = 18 December 2019 | archive-date = 29 October 2019 | archive-url = https://web.archive.org/web/20191029013537/https://www.drugs.com/pregnancy/ranitidine.html | url-status = live}}</ref>
| pregnancy_US = B
| pregnancy_category =
| legal_AU = S2
| routes_of_administration = ], ] (IV)
| legal_US = OTC
| class = ], aka H2 blocker<ref name="Zantac FDA label" />
| legal_status = P/POM <small>(])</small>
| ATC_prefix = A02
| routes_of_administration = Oral, ]
| ATC_suffix = BA02
| ATC_supplemental = <br />{{ATC|A02|BA07}} (ranitidine bismuth citrate)


<!--Pharmacokinetic data--> <!-- Legal status -->
| legal_AU = S4
| bioavailability = 39 to 88%
| legal_AU_comment = /&nbsp;S2 (Pharmacy Medicine)
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = /&nbsp;OTC<ref>{{cite web | title=Nitrosamine impurities in medications: Medications affected | website=] | date=19 March 2021 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/information-health-product/drugs/nitrosamine-impurities/medications-affected.html | access-date=7 January 2024}}</ref><ref>{{cite web | title=Acid Reducer (Ranitidine) Tablet: N-nitrosodimethylamine (NDMA) impurity | website=] | date=6 December 2021 | url=https://recalls-rappels.canada.ca/en/alert-recall/acid-reducer-ranitidine-tablet-n-nitrosodimethylamine-ndma-impurity | access-date=7 January 2024}}</ref><ref>https://pdf.hres.ca/dpd_pm/00003505.PDF {{Bare URL PDF|date=August 2024}}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = /&nbsp;GSL/&nbsp;P<ref>{{cite web | title=Ranitidine 50mg/2ml Solution for Injection and Infusion | website=medicines.org.uk | date=13 October 2021 | url=https://www.medicines.org.uk/emc/product/4453/smpc | access-date=7 January 2024}}</ref><ref>{{cite web | title=Boots Heartburn & Indigestion Relief 75mg Tablets (P) | website=medicines.org.uk | date=3 October 2016 | url=https://www.medicines.org.uk/emc/product/8309/pil | access-date=7 January 2024}}</ref><ref>{{cite web | title=Boots Heartburn & Indigestion Relief 75mg Tablets | website=medicines.org.uk | date=3 October 2016 | url=https://www.medicines.org.uk/emc/product/8308/pil | access-date=7 January 2024}}</ref>
| legal_US = Rx-only
| legal_US_comment = /&nbsp;OTC<ref name="Zantac FDA label" /><ref>{{cite web | title=Zantac 150 | website=DailyMed | date=3 April 2018 | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=530989 | access-date=18 February 2021 | archive-date=4 July 2022 | archive-url=https://web.archive.org/web/20220704051407/https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=530989 | url-status=live }}</ref><ref>{{cite web | title=Ranitidine hydrochloride capsule | website=DailyMed | date=21 November 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bf94bf7-fa11-70be-9f65-fe26a3db5a63 | access-date=7 January 2024}}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="CHMP withdrawl" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = 50% (])<ref name = AHFS2015/>
| protein_bound = 15% | protein_bound = 15%
| metabolism = ] | metabolism = ]: ]s, including ]; other enzymes
| metabolites =
| elimination_half-life = 2&ndash;3 hours
| onset = 55–65&nbsp;minutes (150&nbsp;mg dose)<ref name = "pmid12144582"/><br />55–115&nbsp;minutes (75&nbsp;mg dose)<ref name = "pmid12144582">{{cite journal | vauthors = Gardner JD, Ciociola AA, Robinson M, McIsaac RL | title = Determination of the time of onset of action of ranitidine and famotidine on intra-gastric acidity | journal = Alimentary Pharmacology & Therapeutics | volume = 16 | issue = 7 | pages = 1317–1326 | date = July 2002 | pmid = 12144582 | doi = 10.1046/j.1365-2036.2002.01291.x | s2cid = 34396030 | doi-access = free | title-link = doi }}</ref>
| excretion = 30&ndash;70% ]
| elimination_half-life = 2–3 hours
| duration_of_action =
| excretion = 30–70% ]


<!--Identifiers--> <!-- Identifiers -->
| index2_label = HCl
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 66357-35-5 | CAS_number = 66357-35-5
| CAS_number2_Ref = {{cascite|correct|??}}
| ATC_prefix = A02
| CAS_number2 = 66357-59-3
| ATC_suffix = BA02
| CAS_supplemental =
| PubChem = 657345
| PubChem = 3001055
| PubChem2 = 3033332
| IUPHAR_ligand = 1234
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00863 | DrugBank = DB00863
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | DrugBank2_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank2 = DBSALT000487
| ChemSpiderID = 571454
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 4863
| ChemSpiderID2_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID2 = 43590
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 884KT10YB7 | UNII = 884KT10YB7
| KEGG_Ref = {{keggcite|changed|kegg}} | UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = BK76465IHM
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00422 | KEGG = D00422
| KEGG2_Ref = {{keggcite|correct|kegg}}
| KEGG2 = D00673
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 8776
| ChEBI2_Ref = {{ebicite|changed|EBI}}
| ChEBI2 = 8777
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 512 --> | ChEMBL = 1790041
| ChEMBL2_Ref = {{ebicite|changed|EBI}}
| C=13 | H=22 | N=4 | O=3 | S=1
| ChEMBL2 = 2110372
| molecular_weight = 314.4 g/mol
| NIAID_ChemDB =
| smiles = (=O)\C=C(\NC)NCCSCc1oc(cc1)CN(C)C
| PDB_ligand =
| InChI = 1/C13H22N4O3S/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3/h4-5,9,14-15H,6-8,10H2,1-3H3/b13-9-
| synonyms = Dimethyl amino}ethyl)sulfanyl]methyl}furan-2-yl)methyl]amine
| InChIKey = VMXUWOKSQNHOCA-LCYFTJDEBT

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
<!-- Chemical and physical data -->
| StdInChI = 1S/C13H22N4O3S/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3/h4-5,9,14-15H,6-8,10H2,1-3H3/b13-9-
| IUPAC_name = ''N''-(2-furan-2-yl)methylthio]ethyl)-''N'''-methyl-2-nitroethene-1,1-diamine
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| C = 13 | H = 22 | N = 4 | O = 3 | S = 1
| StdInChIKey = VMXUWOKSQNHOCA-LCYFTJDESA-N
| SMILES = CNC(=C(=O))NCCSCC1=CC=C(O1)CN(C)C
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C13H22N4O3S/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3/h4-5,9,14-15H,6-8,10H2,1-3H3
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = VMXUWOKSQNHOCA-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}
'''Ranitidine''' ({{IPAc-en|icon|r|ə|ˈ|n|ɪ|t|ɨ|d|iː|n}}; trade name '''Zantac''') is a ] ] that inhibits ] production. It is commonly used in treatment of ] disease (PUD) and ] disease (GERD). Ranitidine is also used alongside ] and other antihistamines for the treatment of skin conditions such as ]. Ranitidine is also known to give false positives for ] on drug tests.<ref>{{cite journal|last=Poklis|first=A|coauthors=Hall KV, Still J, Binder SR|title=Ranitidine interference with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay|journal=Journal of analytical toxicology|year=1991|month=March|volume=15|issue=2|pages=101–103|url=http://www.ncbi.nlm.nih.gov/pubmed/2051743|accessdate=13 July 2011|pmid=2051743}}</ref>


'''Ranitidine''', previously sold under the brand name '''Zantac'''{{efn|Zantac in the United States is now a brand of ].}} among others, is a ] used to decrease ] production.<ref name=AHFS2015/> It was commonly used in treatment of ], ], and ].<ref name=AHFS2015/> It can be given by ], ], or ].
==Medical use==
Certain preparations of ranitidine are not available ] (OTC) in various countries. In the United States, 75&nbsp;mg and 150&nbsp;mg tablets are available OTC. Zantac OTC is manufactured by ]. In Australia, packs containing 7 or 14 doses of the 150&nbsp;mg tablet are available in supermarkets, small packs of 150&nbsp;mg and 300&nbsp;mg tablets are ]. Larger doses and pack sizes still require a prescription.


In September 2019, the probable ] ] (NDMA) was discovered in ranitidine products from a number of manufacturers, resulting in recalls.<ref name="HealthCanada">{{cite web | date=13 September 2019 | title=Health Canada assessing NDMA in ranitidine | url=https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/70989a-eng.php | url-status=live | archive-url=https://web.archive.org/web/20190926211206/https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/70989a-eng.php | archive-date=26 September 2019 | access-date=26 September 2019 | website=]}}</ref><ref name="FDA2019NDMA">{{cite web | date=13 September 2019 | title=Statement alerting patients and health care professionals of NDMA found in samples of ranitidine | url=https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine | url-status=live | archive-url=https://web.archive.org/web/20190926210751/https://www.fda.gov/news-events/press-announcements/statement-alerting-patients-and-health-care-professionals-ndma-found-samples-ranitidine | archive-date=26 September 2019 | access-date=26 September 2019 | website=U.S. ] (FDA)}} {{PD-notice}}</ref><ref name="EMA1">{{cite press release | title=EMA to provide guidance on avoiding nitrosamines in human medicines | website=European Medicines Agency | date=13 September 2019 | url=https://www.ema.europa.eu/en/news/ema-provide-guidance-avoiding-nitrosamines-human-medicines | access-date=19 September 2019 | archive-date=31 December 2019 | archive-url=https://web.archive.org/web/20191231050132/https://www.ema.europa.eu/en/news/ema-provide-guidance-avoiding-nitrosamines-human-medicines | url-status=live}}</ref><ref name="FDA NDMA ranitidine">{{cite web | date=28 October 2019 | title=FDA updates and press announcements on NDMA in Zantac (ranitidine) | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine | url-status=live | archive-url=https://web.archive.org/web/20191029011848/https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine | archive-date=29 October 2019 | access-date=28 October 2019 | website=U.S. ] (FDA) | quote=FDA observed the testing method used by a third-party laboratory uses higher temperatures. The higher temperatures generated very high levels of NDMA from ranitidine products because of the test procedure. The FDA published the method for testing angiotensin II receptor blockers (ARBs) for nitrosamine impurities. That method is not suitable for testing ranitidine because heating the sample generates NDMA.<br />FDA recommends using an LC-HRMS testing protocol to test samples of ranitidine. FDA's LC-HRMS testing method does not use elevated temperatures and has shown the presence of much lower levels of NDMA in ranitidine medicines than reported by the third-party laboratory. International regulators using similar LC-MS testing methods have also shown the presence of low levels of NDMA in ranitidine samples.}} {{PD-notice}}</ref> In April 2020, ranitidine was withdrawn from the United States market and suspended in the European Union and Australia due to these concerns.<ref name="FDA Q&A">{{cite web | date=11 October 2019 | title=Questions and Answers: NDMA impurities in ranitidine (commonly known as Zantac) | url=https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-ndma-impurities-ranitidine-commonly-known-zantac | url-status=live | archive-url=https://web.archive.org/web/20191024040431/https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-ndma-impurities-ranitidine-commonly-known-zantac | archive-date=24 October 2019 | access-date=23 October 2019 | website=U.S. ] (FDA)}} {{PD-notice}}</ref><ref name="FDA removal PR">{{cite press release | title=FDA Requests Removal of All Ranitidine Products (Zantac) from the Market | website=U.S. ] (FDA) | date=1 April 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market | access-date=1 April 2020 | archive-date=28 March 2021 | archive-url=https://web.archive.org/web/20210328103217/https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market | url-status=live }} {{PD-notice}}</ref><ref name="EU suspension PR">{{cite press release | title=Suspension of ranitidine medicines in the EU | website=European Medicines Agency | date=30 April 2020 | url=https://www.ema.europa.eu/en/news/suspension-ranitidine-medicines-eu | access-date=2 June 2020 | archive-date=5 January 2021 | archive-url=https://web.archive.org/web/20210105083734/https://www.ema.europa.eu/en/news/suspension-ranitidine-medicines-eu | url-status=live }}</ref><ref name="CHMP withdrawl" /><ref>{{cite web | title=Ranitidine | website=Therapeutic Goods Administration (TGA) | date=2 April 2020 | url=https://www.tga.gov.au/node/882059 | access-date=19 July 2020 | archive-date=29 August 2021 | archive-url=https://web.archive.org/web/20210829025912/https://www.tga.gov.au/alert/ranitidine-0 | url-status=live }}</ref><ref name="2021NIH">{{cite journal | vauthors = Wagner JA, Dinh JC, Lightdale JR, Gold BD, Colombo JM | title = Is this the end for ranitidine? NDMA presence continues to confound | journal = Clinical and Translational Science | volume = 14 | issue = 4 | pages = 1197–1200 | date = July 2021 | pmid = 33934515 | pmc = 8301580 | doi = 10.1111/cts.12995 }}</ref>
Outside the United States and Canada, ranitidine is combined with ] (which acts as a mild ]) as a ] salt (ranitidine bismuth citrate, Tritec), to treat '']'' infections. This combination is usually given with ], an antibiotic.


In 2022, these concerns were confirmed in a Taiwanese nationwide population study finding "significant trends of increased liver cancer risk with an increasing dose of ranitidine" (up to 22% higher than control) and increased gastric, pancreatic, lung{{efn|Gastric, pancreatic, and lung cancer risk increased by up to 26%, 35%, and 17%, respectively, but "only liver cancer displayed a significant association with long-term ranitidine use" and "there was no continuous dose–response relationship among the other individual cancers".<ref name="taiwanstudy" />}} and overall{{efn|Overall cancer risk increased by 10%, ''p'' < 0.001<ref name="taiwanstudy" />}} cancer risk.<ref name="taiwanstudy">{{cite journal | vauthors = Wang CH, Chen II, Chen CH, Tseng YT | title = Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study | journal = International Journal of Environmental Research and Public Health | volume = 19 | issue = 19 | pages = 12469 | date = September 2022 | pmid = 36231768 | pmc = 9566239 | doi = 10.3390/ijerph191912469 | doi-access = free | title-link = doi }}</ref>
Ranitidine's main role is in treating gastric and duodenal ulcers and gastroesophageal reflux disease. It is also used to treat pediatric reflux, where it is preferred over a ], because it does not induce histologically relevant hyperplastic changes in the parietal cells. Liquid formulations are available for administering to children.


<!-- Side effects and mechanism -->
Ranitidine can also be co-administered with NSAIDs to reduce the risk of ulceration.
Common side effects include ]s, and pain or burning sensation if given by injection.<ref name=AHFS2015/> Serious side effects may include cancer,<ref>{{cite news |date=15 February 2023 |title=Zantac's Maker Kept Quiet About Cancer Risks for 40 Years |language=en |work=Bloomberg.com |url=https://www.bloomberg.com/news/features/2023-02-15/zantac-cancer-risk-data-was-kept-quiet-by-manufacturer-glaxo-for-40-years |access-date=20 February 2023 |archive-date=19 February 2023 |archive-url=https://web.archive.org/web/20230219212613/https://www.bloomberg.com/news/features/2023-02-15/zantac-cancer-risk-data-was-kept-quiet-by-manufacturer-glaxo-for-40-years |url-status=live }}</ref> liver problems, a ], ], and the potential of masking ].<ref name=AHFS2015/> It is also linked to an increased risk of ].<ref>{{cite journal | vauthors = Tleyjeh IM, Abdulhak AB, Riaz M, Garbati MA, Al-Tannir M, Alasmari FA, Alghamdi M, Khan AR, Erwin PJ, Sutton AJ, Baddour LM | title = The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e56498 | date = 2013 | pmid = 23469173 | pmc = 3587620 | doi = 10.1371/journal.pone.0056498 | doi-access = free | title-link = doi | bibcode = 2013PLoSO...856498T }}</ref> Ranitidine is an ] that works by blocking ], thus decreasing the amount of acid released by cells of the stomach.<ref name=AHFS2015>{{cite web|title=Ranitidine hydrochloride monograph
|url=https://www.drugs.com/monograph/ranitidine-hydrochloride.html
|publisher=The American Society of Health-System Pharmacists |access-date=1 December 2015 |url-status=live
|archive-url=https://web.archive.org/web/20170909005129/https://www.drugs.com/monograph/ranitidine-hydrochloride.html|archive-date=9 September 2017}}</ref>


<!-- History, society and culture -->
Ranitidine can be administered preoperatively to reduce the risk of aspiration pneumonia. The drug not only increases gastric pH, but also reduces the total output of gastric juice. Ranitidine may have an antiemetic effect when administered preoperatively.
Ranitidine was discovered in England in 1976 and came into commercial use in 1981.<ref>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=444|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA444|url-status=live|archive-url=https://web.archive.org/web/20161220084238/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA444|archive-date=20 December 2016 }}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref><ref>{{cite web |title=eEML - Electronic Essential Medicines List |url=https://list.essentialmeds.org/medicines/179 |access-date=20 February 2023 |website=list.essentialmeds.org |archive-date=20 February 2023 |archive-url=https://web.archive.org/web/20230220211408/https://list.essentialmeds.org/medicines/179 |url-status=live }}</ref> It has been withdrawn at regulator request from most markets, including the United States;<ref name=AHFS2015/> according to the UK ], it has been discontinued globally.<ref name=":1">{{cite web |date=29 August 2018 |title=Ranitidine: medicine to lower stomach acid |url=https://www.nhs.uk/medicines/ranitidine/ |access-date=20 February 2023 |website=nhs.uk |language=en |archive-date=3 December 2021 |archive-url=https://web.archive.org/web/20211203160843/https://www.nhs.uk/medicines/ranitidine/ |url-status=live }}</ref>


{{TOC limit}}
It can be administered IV in intensive care units to critically ill patients (particularly geriatric ones) to reduce the risk of gastric bleeding.


==Former medical uses==
The usual dose of ranitidine is either 150&nbsp;mg twice a day or 300&nbsp;mg once every twenty four hours, usually at night. For ulcer treatment, a 300&nbsp;mg nighttime dose is especially important - as the increase in gastric/duodenal pH promotes healing overnight when the stomach and duodenum are empty. Conversely, for treating reflux, smaller and more frequent doses are more effective.
* Relief of ]<ref name="Zantac FDA label"/>
* Short-term and maintenance therapy of gastric and ]s<ref name="Zantac FDA label"/>
* With ]s (NSAIDs) to reduce the risk of ulceration<ref name="Zantac FDA label"/> ]s (PPIs) are more effective for the prevention of NSAID-induced ulcers.<ref>{{cite web|title=Reflux Remedies: ranitidine|url=http://pharmasight.org/otc/reflux-remedies-ranitidine-zantac/|work=PharmaSight OTC Health|access-date=16 November 2011|url-status=live|archive-url=https://web.archive.org/web/20130112091347/http://pharmasight.org/otc/reflux-remedies-ranitidine-zantac/|archive-date=12 January 2013}}</ref>
* Pathologic gastrointestinal (GI) hypersecretory conditions such as Zollinger–Ellison syndrome
* ] (GORD or GERD)
* ]
* Part of a multidrug regimen for '']'' eradication to minimise the risk of duodenal ulcer recurrence
* Recurrent postoperative ulcer
* Upper GI bleeding
* For prevention of acid-aspiration pneumonitis during surgery, it can be administered preoperatively. The drug increases gastric ], but generally has no effect on gastric volume. In a 2009 meta-analysis comparing the net benefit of PPIs and ranitidine to reduce the risk of aspiration before anaesthesia, ranitidine was found to be more effective than PPIs in reducing the volume of gastric secretions.<ref>{{cite journal | vauthors = Clark K, Lam LT, Gibson S, Currow D | title = The effect of ranitidine versus proton pump inhibitors on gastric secretions: a meta-analysis of randomised control trials | journal = Anaesthesia | volume = 64 | issue = 6 | pages = 652–657 | date = June 2009 | pmid = 19453319 | doi = 10.1111/j.1365-2044.2008.05861.x | s2cid = 7799380 | doi-access = free | title-link = doi }}</ref> Ranitidine may have an anti-emetic effect when administered preoperatively.
* Prevention of ] in critically ill patients<ref>{{cite journal | vauthors = Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R | title = Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012 | journal = Intensive Care Medicine | volume = 39 | issue = 2 | pages = 165–228 | date = February 2013 | pmid = 23361625 | pmc = 2249616 | doi = 10.1007/s00134-012-2769-8 }}</ref>
* Used together with ] as secondary treatment for ]; after first-line ].<ref name="AAFP2003">{{cite journal | vauthors = Tang AW | title = A practical guide to anaphylaxis | journal = American Family Physician | volume = 68 | issue = 7 | pages = 1325–1332 | date = October 2003 | pmid = 14567487 | url = https://www.aafp.org/afp/2003/1001/p1325.html | access-date = 3 February 2017 | url-status = live | archive-url = https://web.archive.org/web/20170110092510/https://www.aafp.org/afp/2003/1001/p1325.html | archive-date = 10 January 2017 }}</ref><ref name=AAP2017>{{cite web|title=Anaphylaxis: Diagnosis and Management in the Rural Emergency Department|url=http://www.aapsus.org/userfiles/files/ajcm4.pdf|publisher=American Journal of Clinical Medicine|access-date=3 February 2017|url-status=live|archive-url=https://web.archive.org/web/20160814133304/http://www.aapsus.org/userfiles/files/AJCM4.pdf|archive-date=14 August 2016}}</ref>


==Contraindication==
Ranitidine used to be administered long term for reflux treatment, sometimes indefinitely. However, PPIs have taken over this role.
Ranitidine has been discontinued globally, according to the ],<ref name=":1" /> and is contraindicated due to excess cancer risk and the ready availability of ] and ].


==Adverse effects==
In some patients with severe reflux, up to 600&nbsp;mg of ranitidine can be administered daily, usually in 4 lots of 150&nbsp;mg. Such a high dose was not unusual in the past, but nowadays a once-a-day PPI is used instead - both for convenience and because they are more effective in raising gastric pH. Patients with ] have been given doses of 6000&nbsp;mg per day without any harm.
These adverse effects for ranitidine have been reported as events in clinical trials:


===Central nervous system===
== Adverse effects ==
Rare reports have been made of ranitidine causing ], ], ], ], and ]. In severely ill, elderly patients, cases of reversible mental confusion, agitation, depression, and ]s have been reported.<ref name="Zantac FDA label" />
Ranitidine appears to decrease mucosal perfusion in patients with acute renal or cardiac failure and increases their risk of death.<ref>{{cite journal |author=Jakob SM, Parviainen I, Ruokonen E, et al. |title=Lack of effect of ranitidine on gastric luminal pH and mucosal PCO2 during the first day in the ICU |journal=] |volume=49 |issue= 3|pages=390–396|year=2005 |doi=10.1111/j.1399-6576.2005.00651.x}}</ref> All drugs in its class decrease gastric intrinsic factor secretion which can significantly reduce absorption of protein-bound vitamin B12 in humans.<ref>{{cite journal |author=Salom IL, Silvis SE, Doscherholmen A. |title=Effect of cimetidine on the absorption of vitamin B12 |journal=Scand J Gastroenterol |volume=17 |issue= 1|pages=129–131|year=1982 |doi=10.3109/00365528209181056 |pmid=7134827}}</ref> Elderly patients taking H2 receptor antagonists are more likely to require vitamin B12 supplementation than those not taking such drugs.<ref>{{cite journal |author=Mitchell SL, Rockwood K. |title=The association between antiulcer medication and initiation of cobalamin replacement in older persons |journal=] |volume=54 |issue= 5|pages=531–534|year=2001 |doi=10.1016/S0895-4356(00)00340-1}}</ref>


===Cardiovascular===
Ranitidine and other histamine H2 receptor antagonists may increase the risk of pneumonia in hospitalized patients.<ref>{{cite journal |author=Mallow S, Rebuck JA, Osler T, et al. |title=Do proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients? |journal=Curr Surg |volume=61 |issue= 5|pages=452–458|year=2004 |doi=10.1016/j.cursur.2004.03.014 |pmid=15475094}}</ref> They may also increase the risk of community-acquired pneumonia in adults and children.<ref> {{cite journal |author=Canani RB, Cirillo P, Roggero P, et al. |title=Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children |journal=] |volume=117 |issue= 5|pages=e817––820|year=2006 |doi=10.1542/peds.2005-1655}} </ref> Multiple studies suggest that use of H2 receptor antagonists such as raniditine may increase the risk of infectious diarrhea, including traveller's diarrhea and salmonella.<ref> {{cite journal |author=Cobelens FGJ, Leentvarr-Kuijpers A, Kleijnen J, Coutinho RA. |title=Incidence and risk factors of diarrhoea in Dutch travellers: Consequences for priorities in pre-travel health advice |journal=Trop Med Intern Health |volume= 3|pages=896–903|year=1998}} </ref><ref> {{cite journal |author=Neal KR, Briji SO, Slack RCB, et al. |title=Recent treatment with H2-antagonists and antibiotics and gastric surgery as risk factors for ] infection |journal=] |volume= 308 |pages=176|year=1994}}</ref><ref>{{cite journal |author=Neal KR, Scott HM, Slack RC, Logan RF. |title=Omeprazole as a risk factor for campylobacter gastroenteritis: Case-control study |journal=] |volume= 312|pages=414–415|year=1996}}</ref><ref>{{cite journal |author=Wickramasinghe LSP, Basu SK. |title=Salmonellosis during treatment with ranitidine |journal=] |volume= 289|pages=1272|year=1984 |doi=10.1136/bmj.289.6454.1272 |issue=6454}}</ref><ref>{{cite journal |author=Ruddell WS, Axon AT, Findlay JM, et al. |title=Effect of cimetidine on gastric bacterial flora |journal=] |volume= i|pages=672–674|year=1980}}</ref>
Arrhythmias such as ], ], ], and premature ventricular beats have also been reported.<ref name="Zantac FDA label"/>


===Gastrointestinal===
H2 antagonists may increase the risk of developing food allergies. Patients who take these agents develop higher levels of IgE against food, whether they had prior antibodies or not.<ref>{{cite journal |author=Untersmayr E, Bakos N, Scholl I, et al. |title=Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients |journal=Faseb J |volume= 19|issue= 6|pages=656–658|year=2005}}</ref> Even months after discontinuation there was still an elevated level of IgE in 6% of patients in this study.
All drugs in the ] class of medicines have the potential to cause vitamin B<sub>12</sub> deficiency, secondary to a reduction in food-bound vitamin B<sub>12</sub> absorption.<ref>{{cite journal | vauthors = Force RW, Nahata MC | title = Effect of histamine H2-receptor antagonists on vitamin B12 absorption | journal = The Annals of Pharmacotherapy | volume = 26 | issue = 10 | pages = 1283–1286 | date = October 1992 | pmid = 1358279 | doi = 10.1177/106002809202601018 | s2cid = 35308626 }}</ref> Elderly patients taking H<sub>2</sub> receptor antagonists are more likely to require B<sub>12</sub> supplementation than those not taking such drugs.<ref>{{cite journal | vauthors = Mitchell SL, Rockwood K | title = The association between antiulcer medication and initiation of cobalamin replacement in older persons | journal = Journal of Clinical Epidemiology | volume = 54 | issue = 5 | pages = 531–534 | date = May 2001 | pmid = 11337218 | doi = 10.1016/S0895-4356(00)00340-1 }}</ref> H<sub>2</sub> blockers may also reduce the absorption of drugs (azole antifungals, calcium carbonate) that require an acidic stomach.<ref>{{cite web|title=Reflux Remedies: ranitidine|url=http://pharmasight.org/overthecounter/2011/11/15/reflux-remedies-ranitidine-zantac/|work=PharmaSight OTC Health|publisher=PharmaSight.org|access-date=16 November 2011|url-status=live|archive-url=https://web.archive.org/web/20170821045645/http://pharmasight.org/overthecounter/2011/11/15/reflux-remedies-ranitidine-zantac/|archive-date=21 August 2017}}</ref> In addition, multiple studies suggest the use of H<sub>2</sub> receptor antagonists such as ranitidine may increase the risk of infectious diarrhoea, including traveller's diarrhoea and salmonellosis.<ref>{{cite journal | vauthors = Cobelens FG, Leentvaar-Kuijpers A, Kleijnen J, Coutinho RA | title = Incidence and risk factors of diarrhoea in Dutch travellers: consequences for priorities in pre-travel health advice | journal = Tropical Medicine & International Health | volume = 3 | issue = 11 | pages = 896–903 | date = November 1998 | pmid = 9855403 }}</ref><ref name="pmid7906170">{{cite journal | vauthors = Neal KR, Briji SO, Slack RC, Hawkey CJ, Logan RF | title = Recent treatment with H2 antagonists and antibiotics and gastric surgery as risk factors for Salmonella infection | journal = BMJ | volume = 308 | issue = 6922 | pages = 176 | date = January 1994 | pmid = 7906170 | pmc = 2542523 | doi = 10.1136/bmj.308.6922.176 }}</ref><ref name="pmid8601113">{{cite journal | vauthors = Neal KR, Scott HM, Slack RC, Logan RF | title = Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study | journal = BMJ | volume = 312 | issue = 7028 | pages = 414–415 | date = February 1996 | pmid = 8601113 | pmc = 2350063 | doi = 10.1136/bmj.312.7028.414 }}</ref><ref>{{cite journal|vauthors=Wickramasinghe LS, Basu SK|title=Salmonellosis during treatment with ranitidine|journal=]|volume=289|pages=1272|year=1984|doi=10.1136/bmj.289.6454.1272|issue=6454|department=Unreviewed reports| doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Ruddell WS, Axon AT, Findlay JM, Bartholomew BA, Hill MJ | title = Effect of cimetidine on the gastric bacterial flora | journal = Lancet | volume = 1 | issue = 8170 | pages = 672–674 | date = March 1980 | pmid = 6103090 | doi = 10.1016/s0140-6736(80)92826-3 | s2cid = 35753958 }}</ref> A 2005 study found that by suppressing acid-mediated breakdown of proteins, ranitidine may lead to an elevated risk of developing food or drug allergies, due to undigested proteins then passing into the GI tract, where sensitisation occurs. Patients who take these agents develop higher levels of ] against food, whether they had prior antibodies or not.<ref name="pmid15671152">{{cite journal | vauthors = Untersmayr E, Bakos N, Schöll I, Kundi M, Roth-Walter F, Szalai K, Riemer AB, Ankersmit HJ, Scheiner O, Boltz-Nitulescu G, Jensen-Jarolim E | title = Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients | journal = FASEB Journal | volume = 19 | issue = 6 | pages = 656–658 | date = April 2005 | pmid = 15671152 | doi = 10.1096/fj.04-3170fje | doi-access = free | s2cid = 18832411 }}</ref> Even months after discontinuation, an elevated level of IgE in 6% of patients was still found in the study.{{Medical citation needed|date=October 2019}}


===Liver===
==History and development==
], liver failure, hepatitis, and ] have been noted, and require immediate discontinuation of the drug.<ref name="Zantac FDA label"/> Blood tests can reveal an increase in ] or ], although in rare instances, severe cases of ] may require a liver ].<ref>{{cite web|url=http://livertox.nlm.nih.gov/Ranitidine.htm|work=] (NIH)|title=Ranitidine: Hepatotoxicity|date=28 June 2016|access-date=25 August 2016|url-status=live|archive-url=https://web.archive.org/web/20160828180136/http://livertox.nlm.nih.gov/Ranitidine.htm|archive-date=28 August 2016}}</ref>
]


===Lungs===
Ranitidine was developed by ], graduate of the ] ], who at the time worked for Glaxo Pharmaceuticals. In an effort to match the success of Smith, Kline & French (prior to the merger of the two companies into ]), Glaxo developed ] as the first histamine H<sub>2</sub>-receptor antagonist. Ranitidine was the result of a ] process using what was by then a fairly refined model of the histamine H<sub>2</sub>-receptor and quantitative structure-activity relationships (]).
Ranitidine and other ] H<sub>2</sub> receptor antagonists may increase the risk of ] in hospitalised patients.<ref>{{cite journal | vauthors = Mallow S, Rebuck JA, Osler T, Ahern J, Healey MA, Rogers FB | title = Do proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients? | journal = Current Surgery | volume = 61 | issue = 5 | pages = 452–458 | year = 2004 | pmid = 15475094 | doi = 10.1016/j.cursur.2004.03.014 }}</ref> Ranitidine increases the risk of community-acquired pneumonia in adults and children.<ref name="pmid16651285">{{cite journal | vauthors = Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, Passariello A, Manguso F, Morelli L, Guarino A | title = Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children | journal = Pediatrics | volume = 117 | issue = 5 | pages = e817–e820 | date = May 2006 | pmid = 16651285 | doi = 10.1542/peds.2005-1655 | s2cid = 23719299 }}</ref><ref name=":0" />


===Blood===
Glaxo refined the model further by replacing the ]-ring of cimetidine with a ]-ring with a ]-containing substituent, and in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile (i.e. fewer ]s), longer-lasting action, and ten times the activity of cimetidine. Ranitidine has 10% the affinity that cimetidine has to ] so it causes fewer side effects, but other H<sub>2</sub> blockers ] and ] have no CYP450 significant interactions.<ref>
] is a rare but known side effect. Drug-induced thrombocytopenia usually takes weeks or months to appear, but may appear within 12&nbsp;hours of drug intake in a sensitised individual. Typically, the platelet count falls to 80% of normal, and thrombocytopenia may be associated with neutropenia and ].<ref name="pmid21455428">{{cite journal | vauthors = Bangia AV, Kamath N, Mohan V | title = Ranitidine-induced thrombocytopenia: A rare drug reaction | journal = Indian Journal of Pharmacology | volume = 43 | issue = 1 | pages = 76–77 | date = February 2011 | pmid = 21455428 | pmc = 3062128 | doi = 10.4103/0253-7613.75676 | doi-access = free | title-link = doi }}</ref>
{{cite book
| title = Goodman & Gilman's The Pharmacological Basis of Therapeutics
| author = Laurence Brunton, John Lazo, Keith Parker
| page = 972
| edition = 11
| year = 2005
| month = August
| publisher = McGraw-Hill
| isbn = 0071422803
| doi = 10.1036/0071422803
| url = http://mhprofessional.com/product.php?isbn=0071422803
}}</ref>


===Skin===
Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. It has since largely been superseded by the even more effective ]s, with ] becoming the biggest-selling drug for many years. When omeprazole and ranitidine were compared in a study of 144 people with severe inflammation and erosions or ulcers of the esophagus, 85% of those treated with omeprazole healed within eight weeks, compared to 50% of those given ranitidine. In addition, the omeprazole group reported earlier relief of heartburn symptoms.<ref>Pelot, Daniel, (M.D.). "''Digestive System : New Drug for Heartburn''". The New Book of Knowledge : Medicine & Health, Grolier : Danbury, Connecticut. 1990. p.262. ISBN 0-7172-8244-9. Library of Congress 82-645223</ref>
Rash, including rare cases of ], and rare cases of hair loss and vasculitis have been seen.<ref name="Zantac FDA label"/>


==References== ==Precautions==
===Disease-related concerns===
Relief of symptoms due to the use of ranitidine does not exclude the presence of a gastric malignancy. In addition, with kidney or liver impairment, ranitidine must be used with caution. It should be avoided in patients with ], as it may precipitate an attack.<ref>{{cite web|title=Ranitidine drug information|url=http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7613#f_warnings-and-precautions|publisher=Lexicomp|url-access=subscription|url-status=live|archive-url=https://web.archive.org/web/20140420014925/http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7613#f_warnings-and-precautions|archive-date=20 April 2014}}</ref><ref>{{cite web|url=https://www.bfarm.de/SharedDocs/Downloads/EN/Drugs/vigilance/PSURs/csp/q-u/ranitidine.pdf?__blob=publicationFile&v=4|title=Ranitidine - core safety profile|website=Bundesinstitut für Arzneimittel und MedizinProdukte|access-date=29 September 2019|archive-date=26 November 2020|archive-url=https://web.archive.org/web/20201126100647/https://www.bfarm.de/SharedDocs/Downloads/EN/Drugs/vigilance/PSURs/csp/q-u/ranitidine.pdf?__blob=publicationFile&v=4|url-status=live}}</ref>

===Children===
In children, the use of gastric acid inhibitors has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia.<ref name="pmid16651285"/> A cohort analysis including over 11,000&nbsp;neonates reported an association of H<sub>2</sub> blocker use, and an increased incidence of ] in very-low-birth-weight (VLBW) neonates.<ref>{{cite journal | vauthors = Guillet R, Stoll BJ, Cotten CM, Gantz M, McDonald S, Poole WK, Phelps DL | title = Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants | journal = Pediatrics | volume = 117 | issue = 2 | pages = e137–e142 | date = February 2006 | pmid = 16390920 | doi = 10.1542/peds.2005-1543 | s2cid = 41491264 }}</ref> In addition, about a six-fold increase in mortality, necrotizing enterocolitis, and infection such as ], pneumonia, ] was reported in patients receiving ranitidine in a cohort analysis of 274 VLBW neonates.<ref>{{cite journal | vauthors = Terrin G, Passariello A, De Curtis M, Manguso F, Salvia G, Lega L, Messina F, Paludetto R, Canani RB | title = Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns | journal = Pediatrics | volume = 129 | issue = 1 | pages = e40–e45 | date = January 2012 | pmid = 22157140 | doi = 10.1542/peds.2011-0796 | doi-access = free | title-link = doi }}</ref>

===Drug tests===
Ranitidine may return a ] result with some commercial urine drug screening kits for testing for drugs of abuse.<ref>{{cite journal | vauthors = Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA | title = Commonly prescribed medications and potential false-positive urine drug screens | journal = American Journal of Health-System Pharmacy | volume = 67 | issue = 16 | pages = 1344–1350 | date = August 2010 | pmid = 20689123 | doi = 10.2146/ajhp090477 | s2cid = 12339028 }}</ref>

{{Anchor|impurities}}

===Cancer-causing due to inherent instability===
{{See also|Valsartan#recalls|Angiotensin II receptor blocker#recalls}}<!-- reason for recalls -->

In June 2019, ] informed the US ] (FDA) that ]-branded and generic ranitidine resulted in very high levels of NDMA in the human body "due to an inherent instability of the ranitidine molecule".<ref name="OG-alert">{{cite web |title=Earliest NDMA alert |url=https://www.valisure.com/valisure-newsroom/valisure-detects-ndma-in-ranitidine |website=www.valisure.com|quote="Valisure discovered the link of Zantac and its generics to the carcinogen NDMA during its routine testing of every batch of every medication, and first notified the FDA of its initial findings in June of 2019"}}</ref><ref name="FDA-2019-P-4281-dkt">{{cite web |author1=Valisure |author2=(and FDA CDER) |author1-link=Valisure |title= Requests FDA to issue a regulation, revise industry guidance, and request a recall and suspend sales of ranitidine from the US market and take such other actions listed in the petition --Valisure FDA Petition, Attachments (and responses) |url=https://www.regulations.gov/docket/FDA-2019-P-4281/document |website=www.regulations.gov |access-date=16 May 2024|quote="ranitidine formed millions of nanograms of NDMA "}}</ref>

In September 2019, the FDA acknowledged that ranitidine medicines, including some products sold under the brand name Zantac, contained a ] impurity called ] (NDMA), classified as a probable human carcinogen, at unacceptable levels.<ref name="FDA2019NDMA" /><ref name="FDA Q&A" /><ref>{{cite web|date=12 September 2019|title=Zantac (ranitidine): Safety Information - NDMA Found in Samples of Some Ranitidine Medicines|url=https://www.fda.gov/safety/medical-product-safety-information/zantac-ranitidine-safety-information-ndma-found-samples-some-ranitidine-medicines|access-date=6 May 2020|publisher=U.S. ] (FDA)|archive-date=6 May 2020|archive-url=https://web.archive.org/web/20200506232435/https://www.fda.gov/safety/medical-product-safety-information/zantac-ranitidine-safety-information-ndma-found-samples-some-ranitidine-medicines|url-status=live}}</ref> ] announced that it was assessing NDMA in ranitidine<ref name="HealthCanada" /> and requested that manufacturers stop the distribution of ranitidine products in Canada until the NDMA levels in the products are found to be safe.<ref name="Health Canada">{{cite web|date=26 September 2019|title=Health Canada requests that companies stop distributing ranitidine drugs in Canada while it assesses NDMA; additional products being recalled - Recalls and safety alerts|url=https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/71029a-eng.php|url-status=live|archive-url=https://web.archive.org/web/20190926211509/https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/71029a-eng.php|archive-date=26 September 2019|access-date=26 September 2019|website=]}}</ref> Health Canada announced that ranitidine drugs were being recalled by Sandoz Canada, Apotex Inc., Pro Doc Limitée, Sanis Health Inc., and Sivem Pharmaceuticals ULC.<ref name="Health Canada" /> The ] (EMA) started a ]-wide review of ranitidine medicines at the request of the ].<ref name="EMA1" /><ref name="EMA2">{{cite press release|title=EMA to review ranitidine medicines following detection of NDMA|website=] (EMA)|date=13 September 2019|url=https://www.ema.europa.eu/en/news/ema-review-ranitidine-medicines-following-detection-ndma|access-date=19 September 2019|archive-date=13 February 2020|archive-url=https://web.archive.org/web/20200213014926/https://www.ema.europa.eu/en/news/ema-review-ranitidine-medicines-following-detection-ndma|url-status=live}}</ref>

In October 2019, the US. FDA observed that the third-party laboratory that found very high levels of NDMA was using higher temperatures in its tests to detect nitrosamine impurities. The NDMA was mostly generated by the added heat, but the higher temperatures are recommended for using a ] method to test for NDMA in ] and ]s.<ref>{{cite web|date=20 September 2019|title=FDA updates and press announcements on Angiotensin II Receptor Blocker (ARB) recalls (Valsartan, Losartan, and Irbesartan)|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan|url-status=live|archive-url=https://web.archive.org/web/20191003024610/https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan|archive-date=3 October 2019|access-date=2 October 2019|website=U.S. ] (FDA)}} {{PD-notice}}</ref> The FDA stated that it recommends using a ] (LC-HRMS) testing protocol to test samples of ranitidine.<ref>{{cite web|title=Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) method for the determination of NDMA in Ranitidine drug substance and drug product|url=https://www.fda.gov/media/130801/download|url-status=live|archive-url=https://web.archive.org/web/20191102045002/https://www.fda.gov/media/130801/download|archive-date=2 November 2019|website=U.S. ] (FDA)|format=PDF|id=FY19-177-DP A-S}} {{PD-notice}}</ref> Its LC-HRMS testing method does not use elevated temperatures, and has shown the presence of much lower levels of NDMA in ranitidine medicines than were reported by the third-party laboratory. International regulators using similar LC-MS testing methods have also shown the presence of lower but still unacceptable levels of NDMA in ranitidine samples.<ref name="FDA NDMA ranitidine" /> The FDA provided additional guidance about using another LC-MS method based on a triple-quadrupole MS platform.<ref name="FDA NDMA ranitidine" /><ref>{{cite web|date=17 October 2019|title=Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the determination of NDMA in Ranitidine drug substance and solid dosage drug product|url=https://www.fda.gov/media/131868/download|url-status=live|archive-url=https://web.archive.org/web/20191102041800/https://www.fda.gov/media/131868/download|archive-date=2 November 2019|website=U.S. ] (FDA)|format=PDF}} {{PD-notice}}</ref>

In September 2019, Sandoz issued a "precautionary distribution stop" of all medicines containing ranitidine,<ref name="SandozStop">{{cite news| vauthors = Bomey N |date=19 September 2019|title=Ranitidine warnings: Generic Zantac distribution halted on cancer fear|website=]|url=https://www.usatoday.com/story/money/2019/09/19/generic-zantac-ranitidine-sandoz-distribution-stop-novartis/2372161001/|access-date=20 September 2019 |archive-date=20 September 2019|archive-url=https://web.archive.org/web/20190920191731/https://www.usatoday.com/story/money/2019/09/19/generic-zantac-ranitidine-sandoz-distribution-stop-novartis/2372161001/|url-status=live}}</ref><ref>{{cite web| vauthors = Palmer E |date=19 September 2019|title=Novartis doesn't wait for FDA investigation and halts distribution of its generic Zantac|url=https://www.fiercepharma.com/manufacturing/novartis-doesn-t-wait-for-fda-investigation-and-halts-distribution-its-generic-zantac|access-date=20 September 2019|website=FiercePharma|quote=Novartis on Wednesday said it was stopping worldwide distribution of its generic versions of the antacid while regulators investigate the fact that the impurity NDMA has been detected in these ranitidine-based drugs. |archive-date=20 September 2019|archive-url=https://web.archive.org/web/20190920222801/https://www.fiercepharma.com/manufacturing/novartis-doesn-t-wait-for-fda-investigation-and-halts-distribution-its-generic-zantac|url-status=live}}</ref> followed a few days later by a recall of ranitidine hydrochloride capsules in the United States.<ref>{{cite web|date=19 September 2019|title=Sandoz ceases distribution of ranitidine product|url=https://www.in-pharmatechnologist.com/Article/2019/09/19/Sandoz-ceases-distribution-of-ranitidine-product|access-date=24 September 2019|website=Pharmaceutical news, Pharma industry, Pharmaceutical manufacturing|archive-date=10 January 2020|archive-url=https://web.archive.org/web/20200110052707/https://www.in-pharmatechnologist.com/Article/2019/09/19/Sandoz-ceases-distribution-of-ranitidine-product|url-status=live}}</ref><ref>{{cite web|date=24 September 2019|title=Sandoz expands recall of antacid|url=https://www.in-pharmatechnologist.com/Article/2019/09/24/Sandoz-expands-recall-of-antacid|access-date=24 September 2019|website=Pharmaceutical news, Pharma industry, Pharmaceutical manufacturing|archive-date=27 January 2020|archive-url=https://web.archive.org/web/20200127002557/https://www.in-pharmatechnologist.com/Article/2019/09/24/Sandoz-expands-recall-of-antacid|url-status=live}}</ref><ref>{{cite press release|title=Sandoz Inc. issues voluntary recall of Ranitidine Hydrochloride capsules 150mg and 300mg due to an elevated amount of unexpected impurity, N-nitrosodimethylamine (NDMA), in the product|publisher=]|via=PR Newswire|date=23 September 2019|url=https://www.prnewswire.com/news-releases/sandoz-inc-issues-voluntary-recall-of-ranitidine-hydrochloride-capsules-150mg-and-300mg-due-to-an-elevated-amount-of-unexpected-impurity-n-nitrosodimethylamine-ndma-in-the-product-300923689.html|archive-url=https://web.archive.org/web/20190924172401/https://www.prnewswire.com/news-releases/sandoz-inc-issues-voluntary-recall-of-ranitidine-hydrochloride-capsules-150mg-and-300mg-due-to-an-elevated-amount-of-unexpected-impurity-n-nitrosodimethylamine-ndma-in-the-product-300923689.html|archive-date=24 September 2019|url-status=live|access-date=24 September 2019}}</ref> The Italian Medicines Agency recalled all ranitidine that uses an ] from Saraca Laboratories.<ref>{{cite news| vauthors = Thomas K |date=19 September 2019|title=Should you keep taking Zantac for your heartburn?|website=]|url=https://www.nytimes.com/2019/09/19/health/zantac-recall.html|access-date=24 September 2019 |archive-date=23 September 2019|archive-url=https://web.archive.org/web/20190923103823/https://www.nytimes.com/2019/09/19/health/zantac-recall.html|url-status=live}}</ref><ref>{{cite news|date=18 September 2019|title=Carcinogen scare sets off global race to contain tainted Zantac|website=]|url=https://www.latimes.com/business/story/2019-09-18/carcinogen-scare-tainted-zantac|access-date=24 September 2019|archive-date=22 September 2019|archive-url=https://web.archive.org/web/20190922125137/https://www.latimes.com/business/story/2019-09-18/carcinogen-scare-tainted-zantac|url-status=live}}</ref><ref>{{cite web|title=Comunicazione AIFA sui farmaci contenenti ranitidina|url=https://www.AIFA.gov.it/-/comunicazione-aifa-sui-farmaci-contenenti-ranitidina|access-date=30 March 2020|website=Agenzia Italiana del Farmaco|location=Rome, Italy|language=it|archive-date=18 April 2020|archive-url=https://web.archive.org/web/20200418062349/https://www.aifa.gov.it/-/comunicazione-aifa-sui-farmaci-contenenti-ranitidina|url-status=live}}</ref> The Federal Union of German Associations of Pharmacists (''Arzneimittelkommission der Deutschen Apotheker'') published a list of recalled products,<ref>{{cite web|date=17 September 2019|title=Online Nachricht: AMK: Liste der (Chargen-)Rückrufe Ranitidin-haltiger Arzneimittel|url=https://www.abda.de/fuer-apotheker/arzneimittelkommission/amk-nachrichten/detail/online-nachricht-amk-liste-der-chargen-rueckrufe-ranitidin-haltiger-arzneimittel/|access-date=20 March 2020|website=Arzneimittelkommission der Deutschen Apotheker (AMK)|language=de|archive-date=20 September 2019|archive-url=https://web.archive.org/web/20190920155324/https://www.abda.de/fuer-apotheker/arzneimittelkommission/amk-nachrichten/detail/online-nachricht-amk-liste-der-chargen-rueckrufe-ranitidin-haltiger-arzneimittel/|url-status=live}}</ref> as did the ] in Australia.<ref>{{cite web|date=17 October 2019|title=Ranitidine|url=https://www.tga.gov.au/alert/ranitidine-0|access-date=19 October 2019|website=]|archive-date=19 October 2019|archive-url=https://web.archive.org/web/20191019025835/https://www.tga.gov.au/alert/ranitidine-0|url-status=live}}</ref>

In November 2019, the FDA stated that its tests found levels of NDMA in ranitidine and nizatidine that are similar to those that one may typically ingest with common foods such as grilled or smoked meats.<ref name="FDA Statement">{{cite press release|title=Statement on new testing results, including low levels of impurities in ranitidine drugs|website=U.S. ] (FDA)|date=1 November 2019|url=https://www.fda.gov/news-events/press-announcements/statement-new-testing-results-including-low-levels-impurities-ranitidine-drugs|archive-url=https://web.archive.org/web/20191102041759/https://www.fda.gov/news-events/press-announcements/statement-new-testing-results-including-low-levels-impurities-ranitidine-drugs|archive-date=2 November 2019|url-status=live|access-date=1 November 2019}} {{PD-notice}}</ref><ref name="FDA Lab tests">{{cite web|date=1 November 2019|title=Laboratory tests - Ranitidine|url=https://www.fda.gov/drugs/drug-safety-and-availability/laboratory-tests-ranitidine|url-status=live|archive-url=https://web.archive.org/web/20191102041800/https://www.fda.gov/drugs/drug-safety-and-availability/laboratory-tests-ranitidine|archive-date=2 November 2019|access-date=1 November 2019|website=U.S. ] (FDA)}} {{PD-notice}}</ref> The FDA also stated that its simulated gastric fluid model tests and simulated intestinal fluid model tests indicated that NDMA is not formed when exposed to acid in the stomach with a normal diet.<ref name="FDA Statement" /><ref name="FDA Lab tests" /> The FDA advised companies to recall their ranitidine if testing shows levels of NDMA above the acceptable daily intake (96 nanograms per day or 0.32 parts per million for ranitidine).<ref name="FDA NDMA ranitidine" /> At the same time, it indicated that some levels of NDMA found in medicines still exceeded the agency's acceptable levels.<ref name="FDA Statement" /><ref name="FDA Lab tests" />

In December 2019, the FDA asked manufacturers of ranitidine and nizatidine products to expand their NDMA testing to include all lots of the medication before making them available to consumers.<ref>{{cite web|date=4 December 2019|title=FDA updates and press announcements on NDMA in Zantac (ranitidine)|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine|url-status=live|archive-url=https://web.archive.org/web/20191206002013/https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-ndma-zantac-ranitidine|archive-date=6 December 2019|access-date=6 December 2019|website=U.S. ] (FDA)|quote=Today, we are announcing that we have asked manufacturers of ranitidine and nizatidine products to expand their testing for NDMA to include all lots of the medication before making them available to consumers. If testing shows NDMA above the acceptable daily intake limit (96 nanograms per day or 0.32 parts per million for ranitidine), the manufacturer must inform the agency and should not release the lot for consumer use.}} {{PD-notice}}</ref>

By the end of 2019, ranitidine had already fallen from the 40th most commonly prescribed medication in the United States in 2018, to 53rd place for 2019, with about 13.6{{nbsp}}million prescriptions for the year, versus nearly 19 million the previous year.<ref>{{cite web | title=Ranitidine - Drug Usage Statistics | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Ranitidine | access-date=25 March 2024 | archive-date=7 December 2021 | archive-url=https://web.archive.org/web/20211207061028/https://clincalc.com/DrugStats/Drugs/Ranitidine | url-status=live }}</ref> This reflects total prescriptions for all of 2019, while safety concerns affected sales in only the final 4 months of the year.

In April 2020, new FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including those at which the product may be exposed during distribution and handling by consumers.<ref name="FDA removal PR" /> The testing also showed that the level of NDMA increases as ranitidine medication ages.<ref name="FDA removal PR" /> These conditions may raise the NDMA level above the acceptable daily intake limit.<ref name="FDA removal PR" /> The EMA completed and issued their EU-wide review at the end of the month and the European Commission suspended all ranitidine products in the EU.<ref>{{cite web |last=EMA |date=30 April 2020 |title=Suspension of ranitidine medicines in the EU |url=https://www.ema.europa.eu/en/news/suspension-ranitidine-medicines-eu |access-date=27 March 2023 |website=European Medicines Agency |language=en |archive-date=5 January 2021 |archive-url=https://web.archive.org/web/20210105083734/https://www.ema.europa.eu/en/news/suspension-ranitidine-medicines-eu |url-status=live }}</ref>

In August 2020, the EMA provided guidance to marketing authorization holders for avoiding the presence of nitrosamine impurities and asked them to review all chemical and biological human medicines for the presence of nitrosamines and to test the products at risk.<ref name="EMA Nitrosamine impurities">{{cite web|date=6 August 2020|title=Nitrosamine impurities|url=https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities|access-date=6 August 2020|website=] (EMA)|archive-date=4 August 2020|archive-url=https://web.archive.org/web/20200804183945/https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral-procedures/nitrosamine-impurities|url-status=live}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> In September 2020, the FDA issued guidance about the control of nitrosamine impurities in human drugs.<ref>{{cite press release|title=FDA Provides Guidance to Industry for Detecting and Preventing Nitrosamines in Drugs|website=U.S. ] (FDA)|date=1 September 2020|url=https://www.fda.gov/news-events/press-announcements/fda-provides-guidance-industry-detecting-and-preventing-nitrosamines-drugs|access-date=1 September 2020|archive-date=1 September 2020|archive-url=https://web.archive.org/web/20200901235705/https://www.fda.gov/news-events/press-announcements/fda-provides-guidance-industry-detecting-and-preventing-nitrosamines-drugs|url-status=live}}</ref><ref>{{cite web|date=1 September 2020|title=Control of Nitrosamine Impurities in Human Drugs|url=https://www.fda.gov/media/141720/download|access-date=1 September 2020|website=U.S. ] (FDA)|format=PDF|archive-date=2 September 2020|archive-url=https://web.archive.org/web/20200902011837/https://www.fda.gov/media/141720/download|url-status=live}} {{PD-notice}}</ref><ref>{{cite report | date = September 2020 | title = Control of Nitrosamine Impurities in Human Drugs | url = https://www.fda.gov/regulatory-information/search-fda-guidance-documents/control-nitrosamine-impurities-human-drugs | publisher = U.S. ] (FDA) | page = | docket = FDA-2020-D-1530 | access-date = 24 June 2022 | archive-url = https://web.archive.org/web/20220601224600/https://www.fda.gov/regulatory-information/search-fda-guidance-documents/control-nitrosamine-impurities-human-drugs | archive-date = 1 June 2022 | url-status = live | df = dmy-all}} {{PD-notice}}</ref> An implementation plan was issued in February 2021.<ref>{{cite report | url=https://www.ema.europa.eu/documents/referral/european-medicines-regulatory-network-approach-implementation-chmp-opinion-pursuant-article-53/2004-nitrosamine-impurities-human-medicines_en.pdf | title=European Medicines Regulatory Network approach for the implementation of the CHMP Opinion pursuant to Article 5(3) of Regulation (EC) No 726/2004 for nitrosamine impurities in human medicines | date=18 February 2021 | id=EMA/425645/2020 | access-date=20 February 2021 | archive-date=4 July 2022 | archive-url=https://web.archive.org/web/20220704051404/https://www.ema.europa.eu/en/documents/referral/european-medicines-regulatory-network-approach-implementation-chmp-opinion-pursuant-article-53/2004-nitrosamine-impurities-human-medicines_en.pdf | url-status=live }}</ref>

In 2022, these concerns were confirmed in a Taiwanese nationwide population study finding "significant trends of increased liver cancer risk with an increasing dose of ranitidine" (22% higher than control) and increased gastric, pancreatic, lung (26%, 35%, and 17% respectively), but "only liver cancer displayed a significant association with long-term ranitidine use" and "there was no continuous dose–response relationship among the other individual cancers".<ref name="taiwanstudy" /> Overall cancer risk also increased by 10% (''p'' < 0.001).<ref name="taiwanstudy" />

The FDA issued revised guidelines about nitrosamine impurities in September 2024.<ref>{{cite web | title=Control of Nitrosamine Impurities in Human Drugs | website=U.S. Food and Drug Administration | date=24 February 2021 | url=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/control-nitrosamine-impurities-human-drugs | access-date=6 September 2024}}</ref>

==== List of recalls ====
In September 2019, ] recalled all ] ranitidine tablets sold in the United States at ], ], and ].<ref>{{cite web|title=Apotex Corp. issues voluntary nationwide recall of Ranitidine tablets 75mg and 150mg (all pack sizes and formats) due to the potential for detection of an amount of unexpected impurity, N-nitrosodimethylamine (NDMA) impurity in the product|website=U.S. ] (FDA)|date=26 September 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/apotex-corp-issues-voluntary-nationwide-recall-ranitidine-tablets-75mg-and-150mg-all-pack-sizes-and|archive-url=https://web.archive.org/web/20190926201621/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/apotex-corp-issues-voluntary-nationwide-recall-ranitidine-tablets-75mg-and-150mg-all-pack-sizes-and|archive-date=26 September 2019|url-status=live|access-date=26 September 2019}} {{PD-notice}}</ref><ref>{{cite web|title=Heartburn drug recalled, removed from shelves over cancer concerns|website=]|date=30 September 2019|url=https://www.upi.com/Top_News/US/2019/09/30/Heartburn-drug-recalled-removed-from-shelves-over-cancer-concerns/7811569853996/?sl=7|access-date=1 October 2019|archive-date=1 October 2019|archive-url=https://web.archive.org/web/20191001090518/https://www.upi.com/Top_News/US/2019/09/30/Heartburn-drug-recalled-removed-from-shelves-over-cancer-concerns/7811569853996/?sl=7|url-status=live}}</ref> These retailers, along with ], removed Zantac and some generics from their shelves.<ref>{{cite news|title=Zantac pulled from shelves by Walgreens, Rite Aid and CVS over carcinogen fears|website=]| vauthors = Garcia SE |date=30 September 2019|url=https://www.nytimes.com/2019/09/30/health/zantac-recall-cancer.html|access-date=3 October 2019 |archive-date=3 October 2019|archive-url=https://web.archive.org/web/20191003093248/https://www.nytimes.com/2019/09/30/health/zantac-recall-cancer.html|url-status=live}}</ref><ref>{{cite web|title=CVS pharmacy statement regarding Zantac and other Ranitidine products|website=CVS Health|date=3 October 2019|url=https://cvshealth.com/newsroom/press-releases/cvs-pharmacy-statement-regarding-zantac-and-other-ranitidine-products|archive-url=https://web.archive.org/web/20191003092104/https://cvshealth.com/newsroom/press-releases/cvs-pharmacy-statement-regarding-zantac-and-other-ranitidine-products|archive-date=3 October 2019|url-status=live|access-date=3 October 2019}}</ref><ref>{{cite news| vauthors = Kazin M |title=Walmart suspends sale of Zantac, other products containing ranitidine over cancer risk|website=Fox Business|date=2 October 2019|url=https://www.foxbusiness.com/markets/walmart-suspends-sale-of-zantac-other-products-containing-ranitidine-over-cancer-risk|access-date=3 October 2019 |archive-date=3 October 2019|archive-url=https://web.archive.org/web/20191003093250/https://www.foxbusiness.com/markets/walmart-suspends-sale-of-zantac-other-products-containing-ranitidine-over-cancer-risk|url-status=live}}</ref><ref>{{cite news| vauthors = Criss D |title=Walmart, CVS, Walgreens pull Zantac and similar heartburn drugs because of cancer worries|website=]|date=30 September 2019|url=https://www.cnn.com/2019/09/30/health/cvs-zantac-pulled-cancer-trnd/index.html|access-date=3 October 2019 |archive-date=3 October 2019|archive-url=https://web.archive.org/web/20191003093248/https://www.cnn.com/2019/09/30/health/cvs-zantac-pulled-cancer-trnd/index.html|url-status=live}}</ref><ref>{{cite news|title=Major U.S. drugstore chains pull Zantac amid carcinogen concern|website=]|date=30 September 2019| vauthors = Edney A |url=https://www.bloomberg.com/news/articles/2019-09-30/walgreens-cvs-take-zantac-off-shelves-as-carcinogen-probed|access-date=3 October 2019 |archive-date=3 October 2019|archive-url=https://web.archive.org/web/20191003093904/https://www.bloomberg.com/news/articles/2019-09-30/walgreens-cvs-take-zantac-off-shelves-as-carcinogen-probed|url-status=live}}</ref>

In October 2019, the ] of the United Kingdom (UK) issued a drug alert for ranitidine "... to proactively communicate the recall to hospitals, pharmacies, dispensing practices, retailers and wholesalers in the UK."<ref name="GSK-UK" /> This included all Zantac-branded preparations,<ref>{{cite web|title=Class 2 Medicines recall: Zantac Injection 50mg/2ml, Zantac Syrup 150mg/10ml, Zantac Tablets 150mg, Zantac Tablets 300mg (EL (19)A 24)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-zantac-injection-50mg-2ml-zantac-syrup-150mg-10ml-zantac-tablets-150mg-zantac-tablets-300mg-el-19-a-24|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=8 October 2019|access-date=30 March 2020|quote=GlaxoSmithKline, trading as Glaxo Welcome Ltd, is recalling all unexpired stock of Zantac (ranitidine hydrochloride) prescription only medicines (POM) from pharmacies.|archive-date=27 December 2019|archive-url=https://web.archive.org/web/20191227235719/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-zantac-injection-50mg-2ml-zantac-syrup-150mg-10ml-zantac-tablets-150mg-zantac-tablets-300mg-el-19-a-24|url-status=live}}</ref><ref>{{cite web|title=Press release – Zantac – MHRA drug alert issued as GlaxoSmithKline recalls all unexpired stock|url=https://www.gov.uk/government/news/zantac-mhra-drug-alert-issued-as-glaxosmithkline-recalls-all-unexpired-stock|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=8 October 2019|access-date=30 March 2020|quote=The MHRA has issued an alert to healthcare professionals, as GlaxoSmithKline is recalling all unexpired stock of four types of Zantac, the medicine used to treat conditions such as heartburn and stomach ulcers.|archive-date=28 December 2019|archive-url=https://web.archive.org/web/20191228004414/https://www.gov.uk/government/news/zantac-mhra-drug-alert-issued-as-glaxosmithkline-recalls-all-unexpired-stock|url-status=live}}</ref> along with all generic preparations of ranitidine from Teva UK Limited,<ref>{{cite web|title=Class 2 Medicines recall: Ranitidine Effervescent Tablets 150mg, Ranitidine Effervescent Tablets 300mg (EL (19)A/27)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-effervescent-tablets-150mg-ranitidine-effervescent-tablets-300mg-el-19-a-27|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=17 October 2019|access-date=30 March 2020|quote=Teva UK Limited trading as ratiopharm GmbH is recalling all unexpired stock of Ranitidine Effervescent Tablets from pharmacies.|archive-date=28 January 2020|archive-url=https://web.archive.org/web/20200128225134/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-effervescent-tablets-150mg-ranitidine-effervescent-tablets-300mg-el-19-a-27|url-status=live}}</ref><ref>{{cite web|title=Press release – Ranitidine – MHRA drug alert issued for Teva UK recall|url=https://www.gov.uk/government/news/ranitidine-mhra-drug-alert-issued-for-teva-uk-recall|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=17 October 2019|access-date=30 March 2020|quote=Teva UK Ltd is recalling unexpired stock of certain batches of 2 types of Ranitidine medicines used to treat conditions such as heartburn and stomach ulcers.|archive-date=28 February 2020|archive-url=https://web.archive.org/web/20200228141449/https://www.gov.uk/government/news/ranitidine-mhra-drug-alert-issued-for-teva-uk-recall|url-status=live}}</ref> Rosemont Pharmaceuticals Limited,<ref>{{cite web|title=Class 2 Medicines recall: Ranitidine 150mg/10ml Oral Solution (EL (19)A/29)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-150mg-10ml-oral-solution-el-19-a-29|website=GOV.uk|location=United Kingdom|publisher=]|date=25 October 2019|access-date=30 March 2020|quote=Rosemont Pharmaceuticals Limited is recalling unexpired stock from pharmacies as a precautionary measure due to possible contamination with an impurity.|archive-date=31 December 2019|archive-url=https://web.archive.org/web/20191231002247/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-150mg-10ml-oral-solution-el-19-a-29|url-status=live}}</ref> Omega Pharma Limited and Galpharm International Limited,<ref>{{cite web|title=Class 2 Medicines recall: Zantac 75 Relief Tablets, Zantac 75 Tablets, Galpharm Indigestion Relief 75mg Tablets, Boots Heartburn & Indigestion Relief 75mg Tablets, Kirkland Indigestion Relief 75mg Tablets, Morrisons Indigestion & Heartburn Relief 75mg Tablets, Boots Heartburn & Indigestion Relief 75mg Tablets (EL (19)A/30)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-zantac-75-relief-tablets-zantac-75-tablets-galpharm-indigestion-relief-75mg-tablets-boots-heartburn-indigestion-relief-75mg-tablets-kirkland-indigestion-relief-75mg-tablets-morrisons-indigestion-heartburn-|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=25 October 2019|access-date=30 March 2020|quote=Omega Pharma Limited and Galpharm International Limited are recalling unexpired stock from pharmacies and retail stores as a precautionary measure due to possible contamination with an impurity.|archive-date=31 December 2019|archive-url=https://web.archive.org/web/20191231101940/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-zantac-75-relief-tablets-zantac-75-tablets-galpharm-indigestion-relief-75mg-tablets-boots-heartburn-indigestion-relief-75mg-tablets-kirkland-indigestion-relief-75mg-tablets-morrisons-indigestion-heartburn-|url-status=live}}</ref> Perrigo Company plc,<ref>{{cite web|title=Press release – Ranitidine – MHRA drug alerts issued as Perrigo recalls prescription only and over-the-counter products|url=https://www.gov.uk/government/news/ranitidine-mhra-drug-alerts-issued-as-perrigo-recalls-prescription-only-and-over-the-counter-products|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=25 October 2019|access-date=30 March 2020|quote=The MHRA has issued alerts to healthcare professionals and retailers, as Perrigo Company plc is recalling all unexpired stock of certain batches of Ranitidine medicines used to treat conditions such as heartburn and stomach ulcers.|archive-date=31 December 2019|archive-url=https://web.archive.org/web/20191231095023/https://www.gov.uk/government/news/ranitidine-mhra-drug-alerts-issued-as-perrigo-recalls-prescription-only-and-over-the-counter-products|url-status=live}}</ref> Creo Pharma Limited and Tillomed Laboratories Limited,<ref>{{cite web|title=Class 2 Medicines Recall: Ranitidine Oral Solution 30mg/ml, PL 31862/0023, Ranitidine 150mg Tablets, PL 11311/0138 (EL(19)A/36)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-oral-solution-30mg-ml-pl-31862-0023-ranitidine-150mg-tablets-pl-11311-0138-el-19-a-36|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=19 November 2019|access-date=30 March 2020|quote=Creo Pharma Limited and Tillomed Laboratories Limited are recalling all unexpired stock of the products listed in this alert.|archive-date=21 January 2020|archive-url=https://web.archive.org/web/20200121181127/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-oral-solution-30mg-ml-pl-31862-0023-ranitidine-150mg-tablets-pl-11311-0138-el-19-a-36|url-status=live}}</ref><ref>{{cite web|title=Press release – Ranitidine Oral Solution and Tablets recall|url=https://www.gov.uk/government/news/ranitidine-oral-solution-and-tablets-recall|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=19 November 2019|access-date=30 March 2020|quote=Ranitidine – MHRA drug alert issued as Creo Pharma Limited and Tillomed Laboratories recall unexpired stock.|archive-date=20 November 2019|archive-url=https://web.archive.org/web/20191120152213/https://www.gov.uk/government/news/ranitidine-oral-solution-and-tablets-recall|url-status=live}}</ref> OTC Concepts Ltd, Relonchem Ltd, Noumed Life Sciences Ltd, and Medreich Plc.,<ref>{{cite web|title=Class 2 Medicines recall: Ranitidine 75mg Tablets, (various liveries) (EL(19)A/37)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-75mg-tablets-various-liveries-el-19-a-37|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=21 November 2019|access-date=30 March 2020|quote=OTC Concepts Ltd, Relonchem Ltd, Noumed Life Sciences Ltd and Medreich Plc. are recalling stock from pharmacies and retail stores as a precautionary measure due to possible contamination with an impurity.|archive-date=21 February 2020|archive-url=https://web.archive.org/web/20200221130923/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-75mg-tablets-various-liveries-el-19-a-37|url-status=live}}</ref><ref>{{cite web|title=Press release – MHRA drug alert: recalls for 13 over-the-counter Ranitidine medicines|url=https://www.gov.uk/government/news/mhra-drug-alert-recalls-for-13-over-the-counter-ranitidine-medicines|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=21 November 2019|access-date=30 March 2020|quote=A drug alert has been issued to retailers and healthcare professionals as 4 companies are recalling batches of certain over-the-counter Ranitidine medicines used to treat conditions such as stomach ulcers and heartburn.|archive-date=22 November 2019|archive-url=https://web.archive.org/web/20191122161922/https://www.gov.uk/government/news/mhra-drug-alert-recalls-for-13-over-the-counter-ranitidine-medicines|url-status=live}}</ref> Accord Healthcare,<ref>{{cite web|title=Class 2 Medicines recall: Ranitidine 150mg Film-Coated Tablets, PL 20075/0063, Ranitidine 300mg Film-Coated Tablets, PL 20075/0064 (EL(19)A/40)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-150mg-film-coated-tablets-pl-20075-0063-ranitidine-300mg-film-coated-tablets-pl-20075-0064-el-19-a-40|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=5 December 2019|access-date=30 March 2020|quote=Accord Healthcare are recalling all unexpired stock of the below products from pharmacies and retail stores as a precautionary measure.|archive-date=4 March 2020|archive-url=https://web.archive.org/web/20200304222737/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-ranitidine-150mg-film-coated-tablets-pl-20075-0063-ranitidine-300mg-film-coated-tablets-pl-20075-0064-el-19-a-40|url-status=live}}</ref> Medley Pharma Limited,<ref>{{cite web|title=Class 2 Medicines Recall: Medley Pharma Limited, Ranitidine 150mg Tablets BP, PL 43870/0026, Ranitidine 300mg Tablets BP, PL 43870/0027 (EL(19)A/41)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-medley-pharma-limited-ranitidine-150mg-tablets-bp-pl-43870-0026-ranitidine-300mg-tablets-bp-pl-43870-0027-el-19-a-41|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=16 December 2019|access-date=30 March 2020|quote=Medley Pharma Limited is recalling all unexpired stock of the below products from pharmacies and retail stores as a precautionary measure.|archive-date=5 March 2020|archive-url=https://web.archive.org/web/20200305080928/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-medley-pharma-limited-ranitidine-150mg-tablets-bp-pl-43870-0026-ranitidine-300mg-tablets-bp-pl-43870-0027-el-19-a-41|url-status=live}}</ref> and Medreich Plc.<ref>{{cite web|title=Class 2 Medicines recall: Medreich PLC, Ranitidine 150mg Tablets, PL 21880/0091, Ranitidine 300mg Tablets, PL 21880/0092 (EL (20)A/05)|url=https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-medreich-plc-ranitidine-150mg-tablets-pl-21880-0091-ranitidine-300mg-tablets-pl-21880-0092-el-20-a-05|website=GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=3 February 2020|access-date=30 March 2020|quote=Medreich Plc is recalling all unexpired stock of the above products from pharmacies and wholesalers as a precautionary measure due to possible contamination with an impurity N-nitrosodimethylamine (NDMA) which has genotoxic and carcinogenic potential.|archive-date=16 June 2020|archive-url=https://web.archive.org/web/20200616081649/https://www.gov.uk/drug-device-alerts/class-2-medicines-recall-medreich-plc-ranitidine-150mg-tablets-pl-21880-0091-ranitidine-300mg-tablets-pl-21880-0092-el-20-a-05|url-status=live}}</ref>

In October 2019, the ] of the United Kingdom issued a supply distribution alert (SDA/2019/005) for all oral formulations of ranitidine.<ref>{{cite web|title=MHRA Central Alerting System – Ranitidine: all oral formulations. Supply disruption.|url=https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=102904|website=CAS.MHRA.GOV.uk|location=United Kingdom|publisher=] (MHRA)|date=15 October 2019|access-date=30 March 2020|quote=All oral formulations of ranitidine are shortly anticipated to be out of stock until further notice. This alert provides healthcare professionals with advice on the management of patients currently taking ranitidine.|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813062133/https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=102904|url-status=live}}</ref>

In October 2019, ] recalled all over-the-counter Zantac in the United States and Canada,<ref>{{cite news|title=Zantac recall widens as Sanofi pulls its drug over carcinogen fears|website=]| vauthors = Thomas K |date=18 October 2019|url=https://www.nytimes.com/2019/10/18/health/zantac-recall-carcinogen-sanofi.html|access-date=18 October 2019 |archive-date=18 October 2019|archive-url=https://web.archive.org/web/20191018170303/https://www.nytimes.com/2019/10/18/health/zantac-recall-carcinogen-sanofi.html|url-status=live}}</ref><ref>{{cite web|title=Sanofi provides update on precautionary voluntary recall of Zantac OTC in U.S.|website=U.S. ] (FDA)|date=23 October 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/sanofi-provides-update-precautionary-voluntary-recall-zantac-otc-us|archive-url=https://web.archive.org/web/20191024035253/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/sanofi-provides-update-precautionary-voluntary-recall-zantac-otc-us|archive-date=24 October 2019|url-status=live|access-date=23 October 2019}} {{PD-notice}}</ref><ref name="FDA NDMA ranitidine"/> ] issued a worldwide recall of ranitidine,<ref>{{cite web|title=Perrigo Company plc issues voluntary worldwide recall of Ranitidine due to possible presence of impurity, N-nitrosodimethylamine (NDMA) impurity in the product|website=U.S. ] (FDA)|date=23 October 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/perrigo-company-plc-issues-voluntary-worldwide-recall-ranitidine-due-possible-presence-impurity-n|archive-url=https://web.archive.org/web/20191024035720/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/perrigo-company-plc-issues-voluntary-worldwide-recall-ranitidine-due-possible-presence-impurity-n|archive-date=24 October 2019|url-status=live|access-date=23 October 2019}} {{PD-notice}}</ref><ref name="FDA NDMA ranitidine"/> ] issued a recall of all ranitidine products in the United States,<ref>{{cite web|title=Dr. Reddy's confirms its voluntary nationwide recall of all Ranitidine products in the U.S. market|website=U.S. ] (FDA)|date=23 October 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/dr-reddys-confirms-its-voluntary-nationwide-recall-all-ranitidine-products-us-market|archive-url=https://web.archive.org/web/20191024035800/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/dr-reddys-confirms-its-voluntary-nationwide-recall-all-ranitidine-products-us-market|archive-date=24 October 2019|url-status=live|access-date=23 October 2019}} {{PD-notice}}</ref><ref name="FDA NDMA ranitidine"/> and Novitium Pharma recalled all ranitidine hydrochloride capsules in the US.<ref>{{cite web|title=Novitium Pharma issues voluntary national recall of Ranitidine Hydrochloride capsules 150mg and 300mg due to an elevated amount of unexpected impurity, N-nitrosodimethylamine (NDMA)|website=U.S. ] (FDA)|date=25 October 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/novitium-pharma-issues-voluntary-national-recall-ranitidine-hydrochloride-capsules-150mg-and-300mg|archive-url=https://web.archive.org/web/20191029011927/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/novitium-pharma-issues-voluntary-national-recall-ranitidine-hydrochloride-capsules-150mg-and-300mg|archive-date=29 October 2019|url-status=live|access-date=28 October 2019}} {{PD-notice}}</ref><ref name="FDA NDMA ranitidine"/>

In November 2019, ], ], American Health Packaging, Golden State Medical Supply, and Precision Dose recalled some lots of ranitidine tablets, capsules, and syrup.<ref>{{cite press release|title=Aurobindo Pharma USA, Inc. initiates voluntary nationwide consumer level recall of 38 lots of Ranitidine tablets 150mg, Ranitidine capsules 150mg, Ranitidine capsules 300mg and ranitidine Syrup 15mg/mL due to the detection of NDMA (Nitrosodimethylamine) impurity|website=U.S. ] (FDA)|date=6 November 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/aurobindo-pharma-usa-inc-initiates-voluntary-nationwide-consumer-level-recall-38-lots-ranitidine|archive-url=https://web.archive.org/web/20191111033706/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/aurobindo-pharma-usa-inc-initiates-voluntary-nationwide-consumer-level-recall-38-lots-ranitidine|archive-date=11 November 2019|url-status=live|access-date=10 November 2019}} {{PD-notice}}</ref><ref>{{cite press release|title=Amneal Pharmaceuticals, LLC. issues voluntary nationwide recall of Ranitidine tablets, USP, 150mg and 300mg, and Ranitidine syrup (Ranitidine Oral Solution, USP), 15 mg/mL, due to possible presence of N-nitrosodimethylamine (NDMA) impurity|website=U.S. ] (FDA)|date=12 November 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/amneal-pharmaceuticals-llc-issues-voluntary-nationwide-recall-ranitidine-tablets-usp-150mg-and-300mg|archive-url=https://web.archive.org/web/20191112234415/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/amneal-pharmaceuticals-llc-issues-voluntary-nationwide-recall-ranitidine-tablets-usp-150mg-and-300mg|archive-date=12 November 2019|url-status=live|access-date=12 November 2019}} {{PD-notice}}</ref><ref>{{cite press release|title=American Health Packaging issues voluntary nationwide recall of Ranitidine syrup (Ranitidine Oral Solution USP) 150 mg/10 mL liquid unit dose cups due to the detection of N-nitrosodimethylamine (NDMA) impurity|website=U.S. ] (FDA)|date=8 November 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/american-health-packaging-issues-voluntary-nationwide-recall-ranitidine-syrup-ranitidine-oral|archive-url=https://web.archive.org/web/20191112234545/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/american-health-packaging-issues-voluntary-nationwide-recall-ranitidine-syrup-ranitidine-oral|archive-date=12 November 2019|url-status=live|access-date=12 November 2019}} {{PD-notice}}</ref><ref>{{cite press release|title=Golden State Medical Supply, Inc. issues a voluntary nationwide recall of Ranitidine hydrochloride 150mg and 300mg capsules (manufactured by Novitium Pharma LLC) due to an elevated amount of unexpected impurity, N-nitrosodimethylamine (NDMA)|website=U.S. ] (FDA)|date=15 November 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/golden-state-medical-supply-inc-issues-voluntary-nationwide-recall-ranitidine-hydrochloride-150mg|archive-url=https://web.archive.org/web/20191123070140/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/golden-state-medical-supply-inc-issues-voluntary-nationwide-recall-ranitidine-hydrochloride-150mg|archive-date=23 November 2019|url-status=live|access-date=22 November 2019}} {{PD-notice}}</ref><ref>{{cite press release|title=Precision Dose Inc. issues voluntary nationwide recall of ranitidine oral solution, USP 150 mg/10 mL due to possible presence of N-nitrosodimethylamine impurity|website=U.S. ] (FDA)|date=19 November 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/precision-dose-inc-issues-voluntary-nationwide-recall-ranitidine-oral-solution-usp-150-mg10-ml-due|archive-url=https://web.archive.org/web/20191123070344/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/precision-dose-inc-issues-voluntary-nationwide-recall-ranitidine-oral-solution-usp-150-mg10-ml-due|archive-date=23 November 2019|url-status=live|access-date=22 November 2019}} {{PD-notice}}</ref>

In December 2019, Glenmark Pharmaceutical Inc., USA, recalled some lots of ranitidine tablets.<ref>{{cite web|title=Glenmark Pharmaceuticals Inc., USA voluntarily recalls all unexpired lots of its Ranitidine tablets and ceases distribution, due to possible presence of N-nitrosodimethylamine (NDMA) impurity|website=U.S. ] (FDA)|date=17 December 2019|url=https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/glenmark-pharmaceuticals-inc-usa-voluntarily-recalls-all-unexpired-lots-its-ranitidine-tablets-and|archive-url=https://web.archive.org/web/20191218221805/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/glenmark-pharmaceuticals-inc-usa-voluntarily-recalls-all-unexpired-lots-its-ranitidine-tablets-and|archive-date=18 December 2019|url-status=live|access-date=18 December 2019}}</ref>

In January 2020, Appco Pharma LLC and Northwind Pharmaceuticals recalled some lots of ranitidine tablets and capsules.<ref>{{cite web|title=Appco Pharma LLC issues voluntary nationwide recall of Ranitidine hydrochloride capsules 150 mg and 300 mg due to an elevated amount of unexpected impurity, N-nitrosodimethylamine (NDMA)|website=U.S. ] (FDA)|date=7 January 2020|url=http://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/appco-pharma-llc-issues-voluntary-nationwide-recall-ranitidine-hydrochloride-capsules-150-mg-and-300|access-date=8 January 2020|archive-date=9 January 2020|archive-url=https://web.archive.org/web/20200109033942/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/appco-pharma-llc-issues-voluntary-nationwide-recall-ranitidine-hydrochloride-capsules-150-mg-and-300|url-status=live}}</ref><ref>{{cite web|title=Denton Pharma, Inc. dba Northwind Pharmaceuticals voluntarily recalls all unexpired lots of its Ranitidine tablets and ceases distribution, due to possible presence of N-nitrosodimethylamine (NDMA) impurity|website=U.S. ] (FDA)|date=6 January 2020|url=http://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/denton-pharma-inc-dba-northwind-pharmaceuticals-voluntarily-recalls-all-unexpired-lots-its|access-date=8 January 2020|archive-date=9 January 2020|archive-url=https://web.archive.org/web/20200109045121/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/denton-pharma-inc-dba-northwind-pharmaceuticals-voluntarily-recalls-all-unexpired-lots-its|url-status=live}}</ref>

In February 2020, American Health Packaging recalled some lots of ranitidine tablets manufactured by Amneal Pharmaceuticals.<ref name="FDA PR">{{cite web|title=American Health Packaging issues voluntary nationwide recall of Ranitidine tablets, USP 150 mg, 100 count unit dose blisters due to the detection of N-nitrosodimethylamine (NDMA) impurity|website=U.S. ] (FDA)|date=27 February 2020|url=http://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/american-health-packaging-issues-voluntary-nationwide-recall-ranitidine-tablets-usp-150-mg-100-count|access-date=28 February 2020|archive-date=28 February 2020|archive-url=https://web.archive.org/web/20200228155144/https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/american-health-packaging-issues-voluntary-nationwide-recall-ranitidine-tablets-usp-150-mg-100-count|url-status=live}} {{PD-notice}}</ref>

In April 2020, the FDA requested a manufacturer's market withdrawal of ranitidine,<ref name="FDA removal PR" /><ref>{{cite web | title=All Ranitidine Products (Zantac): Press Release - FDA Requests Removal | website=U.S. ] (FDA) | date=1 April 2020 | url=https://www.fda.gov/safety/medical-product-safety-information/all-ranitidine-products-zantac-press-release-fda-requests-removal | access-date=6 May 2020 | archive-date=6 May 2020 | archive-url=https://web.archive.org/web/20200506232356/https://www.fda.gov/safety/medical-product-safety-information/all-ranitidine-products-zantac-press-release-fda-requests-removal | url-status=live }}</ref> meaning that ranitidine products would not be available for prescription or over-the-counter sale in the US.<ref name="FDA Q&A" /><ref name="FDA removal PR" />

In April 2020, the ] (CHMP) of the European Medicines Agency recommended the suspension of all ranitidine medicines in the European Union because of the presence of unacceptable levels of NDMA.<ref>{{cite web | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 28-30 April 2020 | website=] (EMA) | date=30 April 2020 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-28-30-april-2020 | access-date=6 May 2020 | archive-date=7 May 2020 | archive-url=https://web.archive.org/web/20200507025647/https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-28-30-april-2020 | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="CHMP withdrawl">{{cite web | title=Ranitidine-containing medicinal products | website=] (EMA) | date=30 April 2020 | url=https://www.ema.europa.eu/en/medicines/human/referrals/ranitidine-containing-medicinal-products | access-date=6 May 2020 | archive-date=6 May 2020 | archive-url=https://web.archive.org/web/20200506155155/https://www.ema.europa.eu/en/medicines/human/referrals/ranitidine-containing-medicinal-products | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref name="EU suspension PR" />

A ranitidine manufacturer requested a re-examination of the decision,<ref name="CHMP withdrawl" /> but in December 2020, the EMA confirmed its recommendation to suspend all ranitidine medicines in the European Union.<ref name="CHMP withdrawl" /> The UK ] (NHS) Web site {{As of|2021|12|lc=y}} said "Ranitidine is not currently available in the UK or globally... It's not yet known whether it will be available again in future." A March 2024 review left the message up.<ref>{{cite web |title=Ranitidine: medicine to lower stomach acid |author= |website=NHS (UK) |date=16 July 2021 |access-date=3 December 2021 |url=https://www.nhs.uk/medicines/ranitidine/ |archive-date=3 December 2021 |archive-url=https://web.archive.org/web/20211203160843/https://www.nhs.uk/medicines/ranitidine/ |url-status=live }}</ref>

In 2021, Solara Active Pharma Sciences, which supplies ranitidine active pharmaceutical ingredient (API), said that it had mitigated the risks of the formation of NDMA during the manufacturing of ranitidine API. The company was granted a revised certificate by the European Directorate for the Quality of Medicines and Healthcare, which proves that the API complies with certain European rules.<ref name=":2" /> ], ], and ] said they had no plans to reintroduce the drug in the EU, but ] considered the possible reintroduction of ranitidine.<ref name=":2">{{cite journal |title=Return of ranitidine being considered by UK manufacturer | vauthors = Connelly D |journal=The Pharmaceutical Journal |date=4 October 2021 |url=https://pharmaceutical-journal.com/article/news/return-of-ranitidine-being-considered-by-uk-manufacturer |access-date=3 December 2021 |archive-date=3 December 2021 |archive-url=https://web.archive.org/web/20211203163055/https://pharmaceutical-journal.com/article/news/return-of-ranitidine-being-considered-by-uk-manufacturer |url-status=live }}</ref> However a control strategy regarding NDMA formation through the end of the product’s shelf life, despite heat, time and digestion due to endogenous formation from the API, would be required.<ref name=":2" />

==Pharmacology==
===Mechanism of action===
Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H<sub>2</sub> receptors found in gastric parietal cells. This results in decreased gastric acid secretion and gastric volume, and reduced hydrogen ion concentration.<ref name="Morgan_Ahlawat2023">{{cite book |vauthors=Morgan KA, Ahlawat R |chapter=Ranitidine |date=2023 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK532989/#:~:text=Ranitidine%20is%20a%20competitive%20inhibitor,kidney%20dysfunction |title=StatPearls |access-date=8 August 2023 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422583 |archive-date=22 March 2023 |archive-url=https://web.archive.org/web/20230322180227/https://www.ncbi.nlm.nih.gov/books/NBK532989/#:~:text=Ranitidine%20is%20a%20competitive%20inhibitor,kidney%20dysfunction |url-status=live }}</ref> Ranitidine's acid-lowering effect is more pronounced for basal and nocturnal acid secretion than it is for food-stimulated acid secretion. Additional indirect effects of ranitidine are decreased pepsin secretion and increased nitrate-reducing bacterial flora.<ref name="Morgan_Ahlawat2023" />

===Pharmacokinetics===
Oral absorption: 50%<ref name="Morgan_Ahlawat2023" />

Protein binding: 15%<ref>{{cite journal |vauthors=Roberts CJ |title=Clinical pharmacokinetics of ranitidine |journal=Clinical Pharmacokinetics |volume=9 |issue=3 |pages=211–221 |date=1984 |pmid=6329583 |doi=10.2165/00003088-198409030-00003|s2cid=21561498 }}</ref>

Metabolism: The major metabolite in the urine is ranitidine ''N''-oxide, which represents less than 4% of the dose. Other metabolites of ranitidine include ranitidine ''S''-oxide (1%) and desmethyl ranitidine (1%).<ref>{{cite web |date=April 2009 |title=Zantac (ranitidine hydrochloride) |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019090s053,019593s042lbl.pdf |access-date=8 August 2023 |publisher=Food and Drug Administration (FDA); GlaxoSmithKline (GSK) |archive-date=21 June 2022 |archive-url=https://web.archive.org/web/20220621172526/https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019090s053,019593s042lbl.pdf |url-status=live }} via {{Webarchive|url=https://web.archive.org/web/20230810225242/https://go.drugbank.com/drugs/DB00863 |date=10 August 2023 }}</ref>

Half-life elimination: With normal renal function, ranitidine taken orally has a half-life of 2.5–3.0 hours.<ref name="Morgan_Ahlawat2023" /> If taken intravenously, the half-life is generally 2.0–2.5 hours in a patient with normal kidney function and normal ] clearance.{{medical citation needed|date=August 2023}} In patients with kidney dysfunction, the half-life may increase to 4 to 5 hours.<ref name="Morgan_Ahlawat2023" />

Excretion: The primary route of excretion is the urine.<ref name="Morgan_Ahlawat2023" /> In addition, about 30% of the orally administered dose is collected in the urine as unabsorbed drug in 24 hours.<ref>{{cite web |date=August 2020 |title=Ranitidine Hydrochloride |url=https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=B0AF5CA1-9189-4C62-BDF1-F1124EC337E7 |access-date=8 August 2023 |website=DailyMed |archive-date=10 August 2023 |archive-url=https://web.archive.org/web/20230810225157/https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=B0AF5CA1-9189-4C62-BDF1-F1124EC337E7 |url-status=live }}</ref>

====Elderly====
In the elderly population, the plasma half-life of ranitidine is prolonged to 3–4 hours secondary to decreased kidney function causing decreased ].<ref name="Zantac FDA label"/>

====Children====
In general, studies of pediatric patients (aged one month to 16 years) have shown no significant differences in pharmacokinetic parameter values in comparison to healthy adults, when correction is made for body weight.<ref name="Zantac FDA label"/>

==History==
] (GSK) as sold in Australia]]
Ranitidine was first prepared in ] as AH19065 by John Bradshaw in the summer of 1977 in the ] research laboratories of ], part of the former ] organisation.<ref>{{cite book| veditors = Lednicer D |title=Chronicles of Drug Discovery|series=ACS Professional Reference Book|volume=3|publisher=John Wiley & Sons|year=1993|isbn=978-0-8412-2733-0|pages=45–81 }}</ref><ref>{{cite patent|country=US|number=4128658|status=patent|title=Aminoalkyl furan derivatives}}</ref> Its development was a response to the first in class histamine H<sub>2</sub> receptor antagonist, ], developed by ] at ], and launched in the United Kingdom as '''Tagamet''' in November 1976. Both companies eventually merged as ] (GSK), following a sequence of mergers and acquisitions, starting with the integration of Allen and Hanbury's Ltd and Glaxo to form Glaxo Group Research in 1979, and ultimately with the merger of Glaxo Wellcome and SmithKline Beecham in 2000. Ranitidine was the result of a ] process using what was by then a fairly refined model of the histamine H<sub>2</sub> receptor and ].

Glaxo refined the model further, by replacing the ] ring of cimetidine with a ] ring with a ]-containing substituent, and in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile (i.e. fewer ]s), longer-lasting action, and 10 times the activity of cimetidine. Ranitidine has 10% of the affinity that cimetidine has to ], so it causes fewer side effects, but other H<sub>2</sub> blockers ] and ] have no CYP450 significant interactions.<ref>{{cite book|title=Goodman & Gilman's The Pharmacological Basis of Therapeutics| vauthors = Brunton L, Lazo J, Parker K |page=972|edition=11|date=August 2005|publisher=McGraw-Hill|isbn=978-0-07-142280-2|url=http://mhprofessional.com/product.php?isbn=0071422803|url-status=dead|archive-url=https://web.archive.org/web/20160411074421/http://www.mhprofessional.com/product.php?isbn=0071422803|archive-date=11 April 2016}}</ref>

Ranitidine was introduced in 1981, and was the world's biggest-selling prescription drug by 1987.<ref>{{Cite web |url=https://academic.oup.com/book/40666/chapter/348351412 |access-date=2024-10-22 |website=academic.oup.com |doi=10.1093/oso/9780199737680.003.0005 |title=Beginning of an Era: The First Blockbuster Drug, Tagamet |date=2014 |isbn=978-0-19-973768-0 | vauthors = Li JJ }}</ref> Subsequently, it was largely superseded by the more effective ] (PPI) class of drugs, with ] becoming the biggest-selling drug for many years.{{Citation needed|date=October 2019}} When omeprazole and ranitidine were compared in a study of 144 people with severe inflammation and erosions or ulcers of the oesophagus, 85% of those treated with omeprazole healed within eight weeks, compared with 50% of those given ranitidine. In addition, the omeprazole group reported earlier relief of heartburn symptoms.<ref>Pelot, Daniel, (M.D.). "''Digestive System : New Drug for Heartburn''". The New Book of Knowledge : Medicine & Health, Grolier : Danbury, Connecticut. 1990. p.262. {{ISBN|0-7172-8244-9}}. Library of Congress 82-645223</ref><ref>{{cite journal | vauthors = Yeomans ND, Tulassay Z, Juhász L, Rácz I, Howard JM, van Rensburg CJ, Swannell AJ, Hawkey CJ | title = A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group | journal = The New England Journal of Medicine | volume = 338 | issue = 11 | pages = 719–726 | date = March 1998 | pmid = 9494148 | doi = 10.1056/NEJM199803123381104 | doi-access = free | title-link = doi }}</ref>

In September 2019, the probable ] ] (NDMA) was discovered in ranitidine products from a number of manufacturers, resulting in recalls; in April 2020, it was withdrawn from the United States market and suspended in Europe and Australia.

==Preparations==
<!-- why would this section need medical cites? {{More medical citations needed|section|date=March 2020}} -->
Preparations of ranitidine products include oral tablets (75, 150, and 300&nbsp;mg), effervescent tablets, and syrups,<ref name="Zantac FDA label"/> and injectable solutions;<ref name=GSK-UK>{{cite web|url=https://GSKpro.com/en-gb/supply/zantac-recall/|title=Zantac recall – UK recall of Zantac (Ranitidine API), incl. Zantac Injection, Zantac Tablets, Zantac Syrup|website=]|location=], ], United Kingdom|date=October 2019|access-date=30 March 2020|archive-date=11 December 2021|archive-url=https://web.archive.org/web/20211211162723/https://gskpro.com/en-gb/|url-status=live}}</ref> with doses of specific ranitidine product preparations are available over-the-counter (OTC) in various countries. In the United Kingdom, only the lowest-strength, 75-mg tablet was available to purchase without a prescription.<ref name="Zantac FDA label"/> In Australia, packs containing seven or 14 doses of the 150-mg tablet were available in supermarkets, small packs of 150-mg and 300-mg tablets were ].{{Medical citation needed|date=October 2019}} Larger doses and pack sizes required a prescription.{{Medical citation needed|date=October 2019}} In the United States, 75- and 150-mg tablets were available OTC.<ref>{{cite web|title=Zantac|website=U.S. ] (FDA)|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021698|access-date=18 October 2019|id=NDA 021698|archive-date=30 October 2019|archive-url=https://web.archive.org/web/20191030012150/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021698|url-status=live}} {{PD-notice}}</ref><ref>{{cite web|title=CVS suspends Zantac sales, as recalls widen over carcinogen fears|website=BioPharma Dive|date=30 September 2019|url=https://www.biopharmadive.com/news/cvs-zantac-voluntary-recall-ndma-carcinogen/563990/|access-date=18 October 2019|archive-date=19 October 2019|archive-url=https://web.archive.org/web/20191019024632/https://www.biopharmadive.com/news/cvs-zantac-voluntary-recall-ndma-carcinogen/563990/|url-status=live}}</ref> In India, it is sold under multiple brand names.<ref name=":0">{{cite web | url=https://medicaldialogues.in/partner/jbcpl/rantac-od | title=Rantac OD 300 | publisher=Medical Dialogues | access-date=19 January 2021 | archive-date=4 July 2022 | archive-url=https://web.archive.org/web/20220704051407/https://medicaldialogues.in/partner/jbcpl/rantac-od | url-status=live }}</ref>

== References ==
{{reflist}} {{reflist}}


==External links== == Notes ==
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== External links ==
{{Histaminergics}}
* {{cite web | title=Ranitidine Injection | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a601164.html }}
{{H2-receptor antagonist}}


{{Drugs for peptic ulcer and GORD}}
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