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			{{Short description|Combination medication for HIV/AIDS}}
	{{Drugbox
			{{Use dmy dates|date=July 2024}}
	| verifiedrevid = 436037914
			{{cs1 config |name-list-style=vanc |display-authors=6}}
			{{Infobox drug
	<!--Combo data-->
			| Verifiedfields = changed
			| Watchedfields = changed
			| verifiedrevid = 451605152
	| type = combo		| type = combo
			| image = Lopinavir and ritonavir.svg
			| width = 222
			| alt =
			| caption =
			| image2 = Lopinavir-ritonavir-Mercury-3D-balls.png
			<!-- Combo data -->
	| component1 = Lopinavir		| component1 = Lopinavir
	| class1 = ]		| class1 = ]
	| component2 = Ritonavir		| component2 = Ritonavir
	| class2 = Protease inhibitor		| class2 = Protease inhibitor (pharmacokinetic booster)
	<!--Clinical data-->		<!-- Clinical data -->
	| tradename =		| tradename = Kaletra, Aluvia
	| Drugs.com = {{drugs.com|monograph|lopinavir-and-ritonavir}}		| Drugs.com = {{drugs.com|monograph|lopinavir-and-ritonavir}}
	| MedlinePlus = a602015		| MedlinePlus = a602015
			| DailyMedID = Kaletra
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
	| pregnancy_US = C		| pregnancy_AU = B3
			| pregnancy_AU_comment =
	| pregnancy_category =
			| pregnancy_category =
	| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
			| routes_of_administration = ]
	| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
			| ATC_prefix = J05
			| ATC_suffix = AR10
			| ATC_supplemental =
			<!-- Legal status -->
			| legal_AU = S4
			| legal_AU_comment =
			| 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 = <ref>{{cite web | title=Kaletra Product information | website=Health Canada | date=19 March 2019 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=77104 | access-date=18 March 2020}}</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 = POM
			| legal_UK_comment =
	| legal_US = Rx
	| legal_status =		| legal_US = Rx-only
			| legal_US_comment = <ref name="Kaletra FDA label" />
	| routes_of_administration = Oral
			| legal_EU = Rx-only
			| legal_EU_comment = <ref name="Kaletra EPAR" />
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
			| legal_UN_comment =
			| legal_status = <!--For countries not listed above-->
	<!--Identifiers-->		<!-- Identifiers -->
			| CAS_number_Ref = {{cascite|changed|??}}
	| CAS_number =
			| CAS_number = 369372-47-4
	| ATC_prefix =
			| CAS_supplemental =
	| ATC_suffix =
	| PubChem =		| PubChem = 11979606
			| IUPHAR_ligand =
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank =		| DrugBank =
			| ChemSpiderID =
			| UNII =
	<!--Chemical data-->
			| KEGG = D02498
			| ChEBI =
			| ChEMBL =
			| NIAID_ChemDB = 003688
			| PDB_ligand =
			| synonyms =
	}}		}}
	'''Lopinavir/ritonavir''' (]) is a ] drug for the treatment of ] infection. It combines ] (not available as a single drug) with a sub-therapeutic dose of ] (trade name ''Norvir'') into a fixed-dose pill.
			<!-- Definition and medical uses -->
	The combination is marketed by ] as '''Kaletra''' (high-income countries) and '''Aluvia''' (low-income countries), as a component of combination therapy to treat HIV/]. The Kaletra formulation has also been used successfully as monotherapy in some studies.<ref>{{cite web |url= http://www.aidsmap.com/iKaletrai-monotherapy-as-effective-as-triple-therapy-for-at-least-18-months/page/1424681/ |title=Kaletra monotherapy as effective as triple therapy for at least 18 months |first1=Christopher |last1=Gadd |first2=Keith |last2=Alcorn |publisher=] |work=aidsmap.com |date=18 August 2006 |accessdate=24 June 2011}}</ref>
			'''Lopinavir/ritonavir''' ('''LPV/r'''), sold under the brand name '''Kaletra''' among others, is a ] ] for the treatment and prevention of ].<ref name=AHFS2016>{{cite web|title=Lopinavir and Ritonavir|url=https://www.drugs.com/monograph/lopinavir-and-ritonavir.html|publisher=The American Society of Health-System Pharmacists|access-date=28 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161220181842/https://www.drugs.com/monograph/lopinavir-and-ritonavir.html|archive-date=20 December 2016}}</ref> It combines ] with a low dose of ].<ref name=AHFS2016/> It is generally recommended for use with other ].<ref name=AHFS2016/> It may be used for prevention after a ] or other potential exposure.<ref name=AHFS2016/> It is taken by mouth as a tablet, capsule, or solution.<ref name=AHFS2016/>
			<!-- Side effects and mechanism -->
	As of 2006, lopinavir/ritonavir forms part of the preferred combination for first-line therapy recommended by the US ].<ref name="dhhs">DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from )</ref> It is available as capsules, tablets and oral solution.
			Common side effects include ], vomiting, feeling tired, headaches, and muscle pains.<ref name=AHFS2016/> Severe side effects may include ], ], and ].<ref name=AHFS2016/> It is commonly used in ] and it appears to be safe.<ref name=AHFS2016/> Both medications are ].<ref name=AHFS2016/> Ritonavir functions by slowing down the breakdown of lopinavir.<ref name=AHFS2016/>
			<!-- History, Society and Culture -->
	==History==
			Lopinavir/ritonavir as a combination medication was approved for use in the United States in 2000.<ref name=AHFS2016/> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>
	Lopinavir was developed by ] in an attempt to improve on the HIV resistance and serum protein-binding properties of the company's earlier protease inhibitor, ritonavir.<ref name="Sham"></ref> Administered alone, lopinavir has insufficient bioavailability; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of ] ].<ref name="Sham" /> Abbott therefore pursued a strategy of co-administering lopinavir with sub-therapeutic doses of ritonavir, and lopinavir is only marketed as a ] with ritonavir. It is the first multi-drug capsule to contain a drug not available individually.
			==Medical uses==
	Lopinavir/ritonavir was approved by the USA ] on 15 September 2000, and in Europe in April 2001. Its patent will expire in the US on June 26, 2016.
			Lopinavir/ritonavir was once a preferred combination for HIV first-line therapy in the United States.<ref name="dhhs">{{cite web | title=Adult and Adolescent Guidelines | website=AIDSinfo | date=4 May 2006 | url=http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=7&ClassID=1 | archive-url=https://web.archive.org/web/20060506193229/http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=7&ClassID=1 | archive-date=6 May 2006 | url-status=dead | access-date=6 May 2006}}</ref> But due to its higher pill burden compared to other protease inhibitor-based regimens and increased gastrointestinal intolerance, it is no longer recommended to treatment-naive patients.<ref>{{cite web |title=What to Start: Initial Combination Regimens for the Antiretroviral-Naive Patient |url=https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start |website=AIDSinfo |access-date=26 August 2020 |page=Table 10. Antiretroviral Components or Regimens Not Recommended as Initial Therapy |date=18 December 2019 |archive-date=31 August 2020 |archive-url=https://web.archive.org/web/20200831213445/https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/11/what-to-start |url-status=dead }}</ref>
	Abbott Laboratories was one of the earliest users of the ], a national synchrotron-radiation light source at ]. One of the early research projects undertaken at the Advanced Photon Source was the Human Immunodeficiency Virus. Using ], researchers found the points of attack of the HIV protease inhibitors – agents that block the breakdown of proteins. Protease inhibitors stop HIV from making new copies of itself by blocking the last step in the process, when the virus attempts to replicate – and out of that discovery came the drug Kaletra.<ref>{{cite web
	| last = Foster
	| first = Catherine
	| title = Research at Argonne helps Abbott Labs develop anti-HIV drug
	| url=http://www.physorg.com/news76606766.html
	| accessdate = 2006-09-04 }}
	</ref>
	==Adverse effects==		==Adverse effects==
	The most common adverse effects observed with lopinavir/ritonavir are ] and ]. In key clinical trials, moderate or severe diarrhea occurred in up to 27% of patients, and moderate/severe nausea in up to 16%.<ref name="PInfo" /> Other common adverse effects include ], ], ], ] and, particularly in children, ].<ref name="PInfo"></ref>		The most common adverse effects observed with lopinavir/ritonavir are ] and ]. In key clinical trials, moderate or severe diarrhea occurred in up to 27% of patients, and moderate/severe nausea in up to 16%.<ref name="Kaletra FDA label" /> Other common adverse effects include ], ], ], ] and, particularly in children, ].<ref name="Kaletra FDA label">{{cite web | title=Kaletra- lopinavir and ritonavir tablet, film coated Kaletra- lopinavir and ritonavir solution | website=DailyMed | date=26 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8290add3-4449-4e58-6c97-8fe1eec972e3 | access-date=18 March 2020}}</ref>
			Lopinavir/ritonavir is anticipated to have varying degrees of interaction with other medications that are also ] and/or ] substrates.<ref>{{cite journal | vauthors = Zhang L, Zhang Y, Huang SM | title = Scientific and regulatory perspectives on metabolizing enzyme-transporter interplay and its role in drug interactions: challenges in predicting drug interactions | journal = Molecular Pharmaceutics | volume = 6 | issue = 6 | pages = 1766–1774 | date = 19 October 2009 | pmid = 19839641 | doi = 10.1021/mp900132e }}</ref>
	Raised liver enzymes and ] (both ] and ]) are also commonly observed during lopinavir/ritonavir treatment.
	Patients with a structural ], preexisting conduction system abnormalities, ], or ] should use lopinavir/ritonavir with caution.<ref name="SafetyLabel200904">FDA Issues Safety Labeling Changes for Kaletra, 2009-04-10, </ref>		People with a structural ], preexisting conduction system abnormalities, ], or ] should use lopinavir/ritonavir with caution.<ref name="SafetyLabel200904">{{cite web | title=FDA Issues Safety Labeling Changes for Kaletra | website=Medscape | date=10 April 2009 | url=http://www.medscape.com/viewarticle/590940 | archive-url=https://web.archive.org/web/20170910144125/http://www.medscape.com/viewarticle/590940 | archive-date=10 September 2017 | url-status=live | access-date=18 March 2020}}</ref>
	On 8 March 2011 the U.S. ] notified healthcare professionals of serious health problems that have been reported in premature babies receiving lopinavir/ritonavir oral solution, probably because of its ] content. They recommend the use should be avoided in premature babies.<ref>Drugs.com: </ref>		In March 2011, the US ] (FDA) notified healthcare professionals of serious health problems that have been reported in premature babies receiving lopinavir/ritonavir oral solution, probably because of its ] content. They recommend the use should be avoided in premature babies.<ref>{{cite web | work = Drugs.com | url = https://www.drugs.com/fda/kaletra-lopinavir-ritonavir-label-change-serious-health-problems-premature-babies-12919.html | title = Kaletra (lopinavir/ritonavir): Label Change - Serious Health Problems in Premature Babies | archive-url = https://web.archive.org/web/20110311020411/http://www.drugs.com/fda/kaletra-lopinavir-ritonavir-label-change-serious-health-problems-premature-babies-12919.html | archive-date=11 March 2011 }}</ref>
	== Access ==		==History==
			] (now, via spinoff, ]) was one of the earliest users of the ] (APS), a national synchrotron-radiation light source at ]. One of the early research projects undertaken at the APS focused on proteins from the human immunodeficiency virus (HIV). Using the APS beam line for ], researchers determined viral protein structures that allowed them to determine their approach to the development of HIV protease inhibitors, a key enzyme target that processes HIV polyproteins after infection, the function of which allows the lifecycle of the virus to proceed. As a result of this ] approach using the Argonne APS, Abbott was able to develop new products that inhibit the protease, and therefore stop virus replication.<ref>{{cite web | vauthors = Foster C | title = Research at Argonne helps Abbott Labs develop anti-HIV drug |url = http://www.physorg.com/news76606766.html |access-date = 4 September 2006 |url-status = live |archive-url = https://web.archive.org/web/20061022054830/http://www.physorg.com/news76606766.html |archive-date = 22 October 2006 }}</ref><ref name="Sham_1998" />
	As a result of high prices and the spread of HIV infection, the government of ] issued a ] on 29 January 2007, to produce and/or import ] versions of lopinavir and ritonavir.<ref></ref> In response, Abbott Laboratories withdrew its registration for lopinavir and seven of their other new drugs in Thailand, citing the Thai government's lack of respect for ]s.<ref></ref> Abbott's attitude has been denounced by several ]s worldwide, including a netstrike initiated by ] and a public call to ] all of Abbott's medicines by the French NGO ].<ref></ref>
			Lopinavir was developed by ] in an attempt to improve upon the company's earlier protease inhibitor, ritonavir, specifically with regard to its serum protein-binding properties (reducing the interference by serum on protease enzyme inhibition) and its HIV resistance profile (reducing the ability of virus to evolve resistance to the drug).<ref name="Sham_1998">{{cite journal | vauthors = Sham HL, Kempf DJ, Molla A, Marsh KC, Kumar GN, Chen CM, Kati W, Stewart K, Lal R, Hsu A, Betebenner D, Korneyeva M, Vasavanonda S, McDonald E, Saldivar A, Wideburg N, Chen X, Niu P, Park C, Jayanti V, Grabowski B, Granneman GR, Sun E, Japour AJ, Leonard JM, Plattner JJ, Norbeck DW | title = ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 12 | pages = 3218–3224 | date = December 1998 | pmid = 9835517 | pmc = 106025 | doi = 10.1128/AAC.42.12.3218 }}</ref> Administered alone, lopinavir has insufficient ]; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of intestinal and hepatic ] ], which would otherwise reduce drug levels through ].<ref name="Sham_1998" />
	==References==
			Lopinavir/ritonavir was approved by the US ] (FDA) in September 2000,<ref>{{cite web | title=Drug Approval Package: Kaletra (Lopinavir/Ritonavir) NDA #21-226 & 21-251 | website=U.S. ] (FDA) | date=20 November 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-226_Kaletra.cfm | access-date=18 March 2020}}</ref><ref>{{cite web|url=https://www.drugs.com/availability/generic-kaletra.html|publisher=Drugs.com|title=Generic Kaletra Availability|access-date=18 February 2020}}</ref> and in the European Union in March 2001.<ref name="Kaletra EPAR">{{cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/kaletra|publisher=] (EMA) |title=Kaletra EPAR |date=17 September 2018 |access-date=18 February 2020}}</ref>
			In March 2020, during the ], the ] announced that it would force AbbVie to license its patents for lopinavir/ritonavir. In response, AbbVie announced that it would cease enforcing its patents on the drug entirely.<ref>{{cite web|url=https://theconversation.com/drug-companies-should-drop-their-patents-and-collaborate-to-fight-coronavirus-135241|title=Drug companies should drop their patents and collaborate to fight coronavirus| vauthors = Bonadio E, Baldini A |publisher=The Conversation|date=1 April 2020}}</ref><ref>{{cite news | title=Inoculating the world may mean reviving old curbs on patents | website=] | date=14 April 2020 | url=https://www.msn.com/en-us/news/world/inoculating-the-world-may-mean-reviving-old-curbs-on-patents/ar-BB12e2Q1 | access-date=16 April 2020 | agency=Bloomberg }}</ref><ref>{{cite news | vauthors = Scheer S | title=Israel approves generic HIV drug to treat COVID-19 despite doubts | website=Reuters | date=19 March 2020 | url=https://www.reuters.com/article/us-health-coronavirus-israel-drug-idUSKBN216237 | access-date=16 April 2020}}</ref>
			==Society and culture==
			===Cost===
			As a result of high prices and the spread of HIV infection, the government of ] issued a ] in January 2007, to produce and/or import ] versions of lopinavir and ritonavir.<ref>{{cite web | url = http://www.cptech.org/ip/health/c/thailand/thai-cl-kaletra_en.pdf | title = Decree of Department of Disease Control, Ministry of Public Health, regarding exploitation of patent on drugs & medical supplies by the government on combination drug between lopinavir & ritonavir | archive-url = https://web.archive.org/web/20110717191941/http://www.cptech.org/ip/health/c/thailand/thai-cl-kaletra_en.pdf | archive-date=17 July 2011 }}</ref> In response, Abbott Laboratories withdrew its registration for lopinavir and seven of their other new drugs in Thailand, citing the Thai government's lack of respect for ]s.<ref></ref> Abbott's attitude has been denounced by several ]s worldwide, including a netstrike initiated by ] and a public call to ] all of Abbott's medicines by the French NGO ].<ref>{{cite web | url = http://www.aides.org/rapport/people-livin-with-hiv-lets-change-the-rule-imposed-by-industry.pdf | title = People Living with HIV: Let's change the rules imposed by the pharmaceutical industry! | date = 1 July 2007 | archive-url = https://web.archive.org/web/20071020044146/http://www.aides.org/rapport/people-livin-with-hiv-lets-change-the-rule-imposed-by-industry.pdf | archive-date=20 October 2007 | work = AIDES }}</ref>
			===Available forms===
			Heat-stable pellets that can be taken by mouth have been developed for children.<ref>{{cite journal | vauthors = Pasipanodya B, Kuwengwa R, Prust ML, Stewart B, Chakanyuka C, Murimwa T, Brophy J, Salami O, Mushavi A, Apollo T | title = Assessing the adoption of lopinavir/ritonavir oral pellets for HIV-positive children in Zimbabwe | journal = Journal of the International AIDS Society | volume = 21 | issue = 12 | pages = e25214 | date = December 2018 | pmid = 30549217 | pmc = 6293134 | doi = 10.1002/jia2.25214 }}</ref>
			==Research==
			{{see also|Coronavirus disease 2019#Research|COVID-19 drug repurposing research}}
			While data for ] looked promising, the benefit in ] is unclear as of March 2020.<ref name=Mc2020>{{cite journal | vauthors = McCreary EK, Pogue JM | title = Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options | journal = Open Forum Infectious Diseases | volume = 7 | issue = 4 | pages = ofaa105 | date = April 2020 | pmid = 32284951 | pmc = 7144823 | doi = 10.1093/ofid/ofaa105 | doi-access = free }}</ref> In 2020, a non-blinded, randomized trial found lopinavir/ritonavir was not useful to treat severe ].<ref>{{cite journal | vauthors = Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C | title = A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19 | journal = The New England Journal of Medicine | volume = 382 | issue = 19 | pages = 1787–1799 | date = May 2020 | pmid = 32187464 | pmc = 7121492 | doi = 10.1056/NEJMoa2001282 | quote = This randomized trial found that lopinavir–ritonavir treatment added to standard supportive care was not associated with clinical improvement or mortality in seriously ill patients with Covid-19 different from that associated with standard care alone. | doi-access = free }}</ref><ref name=Mc2020/> In this trial the medication was started typically around 13 days after the start of symptoms.<ref name=Mc2020/>
			== References ==
	{{reflist}}		{{reflist}}
			== External links ==
	{{HIVpharm}}
			* {{cite web | title=Fact sheet on lopinavir and ritonavir (Lpv/R) oral pellets | website=] (WHO) | url=https://www.who.int/hiv/pub/toolkits/iatt-factsheet-lopinavir-ritonavir/en/ | archive-url=https://web.archive.org/web/20151121102208/http://www.who.int/hiv/pub/toolkits/iatt-factsheet-lopinavir-ritonavir/en/ | url-status=dead | archive-date=21 November 2015 }}
			{{Antiretroviral drug}}
			{{Portal bar | Medicine | Viruses }}
			{{Authority control}}
			{{DEFAULTSORT:Lopinavir Ritonavir}}
			]
	]		]
			]
			]
			]
			]
			]