# Saquinavir

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Chemical compound

Pharmaceutical compound

Saquinavir Clinical data Trade names Invirase, Fortovase Other names SQV AHFS/Drugs.com Monograph MedlinePlus a696001 License data EU EMA: by INN US DailyMed: Saquinavir Pregnancy category AU: B1[1] Routes of administration By mouth ATC code J05AE01 (WHO) Legal status Legal status AU: S4 (Prescription only)[2] US: ℞-only Pharmacokinetic data Bioavailability ~4% (without ritonavir boosting)[3] Protein binding 98% Metabolism Liver, mainly by CYP3A4 Elimination half-life 9–15 hours Excretion feces (81%) and urine (3%) Identifiers IUPAC name (2S)-N-[(2S,3R)-4-[(3S)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinolin-2-ylformamido)butanediamide CAS Number 127779-20-8 Y PubChem CID 441243 IUPHAR/BPS 4813 DrugBank DB01232 Y ChemSpider 390016 Y UNII L3JE09KZ2F KEGG D00429 Y ChEMBL ChEMBL114 Y NIAID ChemDB 000640 PDB ligand ROC (PDBe, RCSB PDB) CompTox Dashboard (EPA) DTXSID6044012 Chemical and physical data Formula C38H50N6O5 Molar mass 670.855 g·mol−1 3D model (JSmol) Interactive image SMILES O=C(N)C[C@H](NC(=O)c1nc2c(cc1)cccc2)C(=O)N[C@@H](Cc3ccccc3)[C@H](O)CN5[C@H](C(=O)NC(C)(C)C)C[C@@H]4CCCC[C@@H]4C5 InChI InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1 Y Key:QWAXKHKRTORLEM-UGJKXSETSA-N Y (verify)

**Saquinavir**, sold under the brand name **Invirase** among others, is an [antiretroviral medication](/source/Antiretroviral_medication) used together with other medications to treat or prevent [HIV/AIDS](/source/HIV%2FAIDS).[4] Typically it is used with [ritonavir](/source/Ritonavir) or [lopinavir/ritonavir](/source/Lopinavir%2Fritonavir) to increase its effect.[4] It is taken [by mouth](/source/By_mouth).[4]

Common side effects include nausea, vomiting, diarrhea, and feeling tired.[4] More serious side effects include problems with [QT prolongation](/source/QT_prolongation), [heart block](/source/Heart_block), [high blood lipids](/source/Hyperlipidemia), and liver problems.[4] It appears to be safe in pregnancy.[4] It is in the [protease inhibitor](/source/Protease_inhibitor_(pharmacology)) class and works by blocking the [HIV protease](/source/HIV_protease).[4]

Saquinavir was patented in 1988 and first sold in 1995.[5][6]

## Medical uses

Saquinavir is used together with other medications to treat or prevent [HIV/AIDS](/source/HIV%2FAIDS).[4] Typically it is used with [ritonavir](/source/Ritonavir) or [lopinavir/ritonavir](/source/Lopinavir%2Fritonavir) to increase its effect.[4]

## Side effects

The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including [diarrhoea](/source/Diarrhoea), [nausea](/source/Nausea), loose stools and abdominal discomfort. Invirase is better tolerated than Fortovase.[*[medical citation needed](https://en.wikipedia.org/wiki/Wikipedia:Identifying_reliable_sources_(medicine))*]

## Bioavailability and drug interactions

Saquinavir, in the Invirase formulation, has a low and variable oral bioavailability, when given alone. The Fortovase formulation at the standard dosage delivers approximately eightfold more active drug than Invirase, also at the standard dosage.[7]

In the clinic, it was found that the oral bioavailability of saquinavir in both formulations significantly increases when patients also receive the PI [ritonavir](/source/Ritonavir). For patients, this has the major benefit that they can take less saquinavir, while maintaining sufficient saquinavir blood plasma levels to efficiently suppress the replication of HIV.[*[medical citation needed](https://en.wikipedia.org/wiki/Wikipedia:Identifying_reliable_sources_(medicine))*]

The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the [cytochrome P450](/source/Cytochrome_P450_oxidase) [3A4](/source/CYP3A4) isozyme. Normally, this enzyme metabolizes saquinavir to an inactive form, but with the ritonavir inhibiting this enzyme, the saquinavir blood plasma levels increased considerably. Additionally, ritonavir also inhibits multidrug transporters, although to a much lower extent.[*[medical citation needed](https://en.wikipedia.org/wiki/Wikipedia:Identifying_reliable_sources_(medicine))*]

Unlike other protease inhibitors, the absorption of saquinavir seems to be improved by [omeprazole](/source/Omeprazole).[8]

## Mechanism of action

Saquinavir is a [protease inhibitor](/source/Protease_inhibitor_(pharmacology)). [Proteases](/source/Protease) are enzymes that cleave protein molecules into smaller fragments. HIV protease is vital for both viral replication within the cell and release of mature viral particles from an infected cell. Saquinavir binds to the active site of the viral protease and prevents cleavage of viral polyproteins, preventing maturation of the virus. Saquinavir inhibits both [HIV-1](/source/Subtypes_of_HIV) and HIV-2 proteases.[9]

## History

New HIV infections and deaths, before and after the FDA approval of "highly active antiretroviral therapy",[10] of which saquinavir, ritonavir and indinavir were key as the first three protease inhibitors.Cully M (28 November 2018). ["Protease inhibitors give wings to combination therapy"](https://www.nature.com/articles/d42859-018-00015-7#:~:text=The%20first%20protease%20inhibitor%20to,and%20indinavir%2C%20were%20also%20approved.). *Nature Research*. Open Publishing. Retrieved 28 October 2020. As a result of the new therapies, HIV deaths in the United States fell dramatically within two years.[10]

Saquinavir was developed by the pharmaceutical company [Roche](/source/Hoffmann-La_Roche).[11] Saquinavir was the sixth antiretroviral and the first protease inhibitor approved by the US [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA), leading [ritonavir](/source/Ritonavir) and [indinavir](/source/Indinavir) by a few months.[12] This new class of antiretrovirals played a critical role in the development of highly active antiretroviral therapy (HAART), which helped significantly lower the risk of death from AIDS-related causes, as seen by a reduction of the annual U.S. HIV-associated death rate, from over 50,000 to about 18,000 over a period of two years.[10][13]

Roche requested and received approval of Invirase via the FDA's "Accelerated Approval" program—a process designed to speed drugs to market for the treatment of serious diseases—a decision that was controversial, as AIDS activists disagreed over the benefits of thorough testing versus early access to new drugs.[14][*[better source needed](https://en.wikipedia.org/wiki/Wikipedia:Verifiability#Questionable_sources)*] It was approved again on November 7, 1997, as Fortovase,[15] a soft gel capsule reformulated for improved [bioavailability](/source/Bioavailability). Roche announced in May 2005 that, given reduced demand, Fortovase would cease being marketed early in 2006, in favor of Invirase boosted with [ritonavir](/source/Ritonavir),[16] owing to the ability of the latter co-formulated drug to inhibit the [enzyme that metabolizes the AIDS drugs](/source/CYP3A4).[*[citation needed](https://en.wikipedia.org/wiki/Wikipedia:Citation_needed)*]

## Society and culture

### Economics

As of 2015[\[update\]](https://en.wikipedia.org/w/index.php?title=Saquinavir&action=edit), it is not available as a [generic medication](/source/Generic_medication).[17]

### Formulations

Two formulations have been marketed:

- a hard-gel capsule formulation of the [mesylate](/source/Mesylate), with trade name Invirase, which requires combination with [ritonavir](/source/Ritonavir) to increase the saquinavir [bioavailability](/source/Bioavailability);

- a soft-gel capsule formulation of saquinavir ([microemulsion](/source/Microemulsion),[18] orally-administered formulation), with trade name Fortovase, which was discontinued worldwide in 2006.[19]

## References

1. **[^](#cite_ref-Drugs.com_pregnancy_1-0)** ["Saquinavir Use During Pregnancy"](https://www.drugs.com/pregnancy/saquinavir.html). *Drugs.com*. 20 March 2018. Retrieved 28 January 2020.

1. **[^](#cite_ref-Invirase_PI_2-0)** Roche Products Pty Limited (6 November 2018). ["Invirase® (Saquinavir mesilate)"](https://web.archive.org/web/20230108234102/https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropinvir10814). *Australian Product Information*. Archived from [the original](https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropinvir10814) on 8 January 2023. Retrieved 8 January 2023 – via MedAdvisor International Pty Ltd.

1. **[^](#cite_ref-Invirase_label_3-0)** ["Invirase- saquinavir mesylate capsule INVIRASE- saquinavir mesylate tablet, film coated"](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c00d1607-ac36-457b-a34b-75ad74f9cf0a). *DailyMed*. 26 December 2019. Retrieved 28 January 2020.

1. ^ [***a***](#cite_ref-AHFS2015_4-0) [***b***](#cite_ref-AHFS2015_4-1) [***c***](#cite_ref-AHFS2015_4-2) [***d***](#cite_ref-AHFS2015_4-3) [***e***](#cite_ref-AHFS2015_4-4) [***f***](#cite_ref-AHFS2015_4-5) [***g***](#cite_ref-AHFS2015_4-6) [***h***](#cite_ref-AHFS2015_4-7) [***i***](#cite_ref-AHFS2015_4-8) ["Saquinavir"](https://www.drugs.com/monograph/saquinavir.html). The American Society of Health-System Pharmacists. [Archived](https://web.archive.org/web/20150908033239/http://www.drugs.com/monograph/saquinavir.html) from the original on 8 September 2015. Retrieved 5 September 2015.

1. **[^](#cite_ref-Min2006_5-0)** Minor LK (2006). [*Handbook of Assay Development in Drug Discovery*](https://books.google.com/books?id=RmrLBQAAQBAJ&pg=PA117). Hoboken: CRC Press. p. 117. [ISBN](/source/ISBN_(identifier)) [9781420015706](https://en.wikipedia.org/wiki/Special:BookSources/9781420015706). [Archived](https://web.archive.org/web/20160331125835/https://books.google.com/books?id=RmrLBQAAQBAJ&pg=PA117) from the original on 31 March 2016.

1. **[^](#cite_ref-Fis2006_6-0)** Fischer J, Ganellin CR (2006). [*Analogue-based Drug Discovery*](https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA509). John Wiley & Sons. p. 509. [ISBN](/source/ISBN_(identifier)) [9783527607495](https://en.wikipedia.org/wiki/Special:BookSources/9783527607495).

1. **[^](#cite_ref-7)** ["Fortovase"](https://web.archive.org/web/20200428232636/https://www.drugs.com/pro/fortovase.html). *Drugs.com*. 22 March 2019. Archived from [the original](https://www.drugs.com/pro/fortovase.html) on 28 April 2020. Retrieved 28 January 2020.

1. **[^](#cite_ref-8)** Winston A, Back D, Fletcher C, Robinson L, Unsworth J, Tolowinska I, et al. (June 2006). ["Effect of omeprazole on the pharmacokinetics of saquinavir-500 mg formulation with ritonavir in healthy male and female volunteers"](https://doi.org/10.1097%2F01.aids.0000233573.41597.8a). *AIDS*. **20** (10): 1401–1406. [doi](/source/Doi_(identifier)):[10.1097/01.aids.0000233573.41597.8a](https://doi.org/10.1097%2F01.aids.0000233573.41597.8a). [PMID](/source/PMID_(identifier)) [16791014](https://pubmed.ncbi.nlm.nih.gov/16791014). [S2CID](/source/S2CID_(identifier)) [44506039](https://api.semanticscholar.org/CorpusID:44506039).

1. **[^](#cite_ref-9)** Dolin R, Masur H, Saag MS, eds. (1999). [*AIDS Therapy*](https://books.google.com/books?id=oeJrAAAAMAAJ&q=Saquinavir+inhibits+both+HIV-1+HIV-2+proteases). Churchill Livingstone. p. 129. [ISBN](/source/ISBN_(identifier)) [9780443075926](https://en.wikipedia.org/wiki/Special:BookSources/9780443075926).

1. ^ [***a***](#cite_ref-MMWR0621_10-0) [***b***](#cite_ref-MMWR0621_10-1) [***c***](#cite_ref-MMWR0621_10-2) Centers for Disease Control and Prevention (CDC) (3 June 2011). ["HIV Surveillance—United States, 1981-2008"](https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6021a2.htm). *Morbidity and Mortality Weekly Report*. **60** (21): 689–693. [PMID](/source/PMID_(identifier)) [21637182](https://pubmed.ncbi.nlm.nih.gov/21637182). [Archived](https://web.archive.org/web/20131109001606/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6021a2.htm) from the original on 9 November 2013. Retrieved 8 November 2013.

1. **[^](#cite_ref-11)** Hilts PJ (8 December 1995). ["F.D.A. Backs A New Drug To Fight AIDS"](https://www.nytimes.com/1995/12/08/us/fda-backs-a-new-drug-to-fight-aids.html). *New York Times*. Retrieved 28 October 2020.

1. **[^](#cite_ref-12)** ["Antiretroviral Drug Discovery and Development"](https://www.niaid.nih.gov/diseases-conditions/antiretroviral-drug-development). *NIH*. 26 November 2018. Retrieved 29 October 2020.

1. **[^](#cite_ref-13)** The CDC, in its *Morbidity and Mortality Weekly Report,* ascribes this to "highly active antiretroviral therapy", without mention of either of these drugs, see the preceding citation. A further citation is needed to make this accurate connection between this drop and the introduction of the protease inhibitors.

1. **[^](#cite_ref-14)** AIDS Community Research Initiative of America. ["Drugs! Drugs! Drugs! An Overview of the Approved Anti-HIV Medications"](http://www.thebody.com/content/art14169.html). The Body. [Archived](https://web.archive.org/web/20131109001602/http://www.thebody.com/content/art14169.html) from the original on 9 November 2013. Retrieved 20 February 2013.

1. **[^](#cite_ref-15)** ["Drug Approval Package: Fortovase/Saquinavir NDA 20828"](https://web.archive.org/web/20200128010336/https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020828_fortovase_toc.cfm). *U.S. [Food and Drug Administration](/source/Food_and_Drug_Administration) (FDA)*. 24 December 1999. Archived from [the original](https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020828_fortovase_toc.cfm) on 28 January 2020. Retrieved 28 January 2020.

1. **[^](#cite_ref-16)** ["Withdrawal of Fortovase (PDF)"](https://web.archive.org/web/20060514173628/http://www.rocheusa.com/products/FTVDearDoctorFINAL.pdf) (PDF). Archived from [the original](http://www.rocheusa.com/products/FTVDearDoctorFINAL.pdf) (PDF) on 14 May 2006.

1. **[^](#cite_ref-17)** ["Generic Invirase Availability"](https://www.drugs.com/availability/generic-invirase.html). *Drugs.com*. Retrieved 9 July 2020.

1. **[^](#cite_ref-18)** Gibaud S, Attivi D (August 2012). ["Microemulsions for oral administration and their therapeutic applications"](https://hal.archives-ouvertes.fr/hal-00706176/file/Microemulsion%20oral%20delivery.pdf) (PDF). *Expert Opinion on Drug Delivery*. **9** (8): 937–951. [doi](/source/Doi_(identifier)):[10.1517/17425247.2012.694865](https://doi.org/10.1517%2F17425247.2012.694865). [PMID](/source/PMID_(identifier)) [22663249](https://pubmed.ncbi.nlm.nih.gov/22663249). [S2CID](/source/S2CID_(identifier)) [28468973](https://api.semanticscholar.org/CorpusID:28468973).

1. **[^](#cite_ref-19)** ["Roche to discontinue the sale and distribution of Fortovase (saquinavir)"](https://web.archive.org/web/20150222180953/http://www.news-medical.net/news/2005/05/18/10187.aspx). *News-Medical.Net*. 18 May 2005. Archived from [the original](http://www.news-medical.net/news/2005/05/18/10187.aspx) on 22 February 2015.

## External links

- ["Saquinavir"](https://web.archive.org/web/20180827202323/https://druginfo.nlm.nih.gov/drugportal/name/Saquinavir). *Drug Information Portal*. U.S. National Library of Medicine. Archived from [the original](https://druginfo.nlm.nih.gov/drugportal/name/saquinavir) on 27 August 2018.

v t e Antiviral drugs: antiretroviral drugs used against HIV (primarily J05) Capsid inhibitors Lenacapavir (LEN) Entry/fusion inhibitors (Discovery and development) gp41 (Enfuvirtide (ENF, T-20))◊ CCR5 (Maraviroc (MVC) Vicriviroc†, Cenicriviroc†, Leronlimab†) CD4 (Ibalizumab (IBA), Semzuvolimab§) gp120 (Fostemsavir (FTR)) Integrase inhibitors (Integrase strand transfer inhibitors (INSTI)) Bictegravir (BIC) Cabotegravir (CAB) Dolutegravir (DTG)# Elvitegravir (EVG) Raltegravir (RAL)# BI 224436† MK-2048† Maturation inhibitors Bevirimat† BMS-955176§ Fipravirimat§ Protease Inhibitors (PI) (Discovery and development) 1st generation Amprenavir (APV)‡ Fosamprenavir (FPV) Indinavir (IDV)◊ Lopinavir (LPV) Nelfinavir (NFV)◊ Ritonavir (RTV)# Saquinavir (SQV)◊ 2nd generation Atazanavir (ATV)°# Darunavir (DRV)°# Tipranavir (TPV)◊ TMC-310911§ Reverse-transcriptase inhibitors (RTIs) Nucleoside and nucleotide (NRTI) Nucleoside analogues/NRTIs: Abacavir (ABC)# Didanosine (ddI)◊ Emtricitabine (FTC) Islatravir (ISL) Lamivudine (3TC)# Stavudine (d4T)◊ Zalcitabine (ddC)‡ Zidovudine (AZT, ZDV)# Amdoxovir† Apricitabine† Censavudine† Elvucitabine† Racivir† Stampidine† Nucleotide analogues/NtRTIs: Tenofovir disoproxil (TDF)# Tenofovir alafenamide (TAF) Non-nucleoside (NNRTI) (Discovery and development) 1st generation Efavirenz (EFV)# Nevirapine (NVP)# Delavirdine (DLV)‡ 2nd generation diarylpyrimidines Dapivirine (DPV) Etravirine (ETR) Rilpivirine (RPV) Doravirine (DOR) Elsulfavirine (ESV) Combined formulations Abacavir/lamivudine# Abacavir/dolutegravir/lamivudine° Abacavir/lamivudine/zidovudine Atazanavir/cobicistat Bictegravir/emtricitabine/tenofovir alafenamide° Cabotegravir/rilpivirine Darunavir/cobicistat Darunavir/cobicistat/emtricitabine/tenofovir alafenamide° Dolutegravir/emtricitabine/tenofovir alafenamide Dolutegravir/lamivudine° Dolutegravir/lamivudine/tenofovir alafenamide° Dolutegravir/lamivudine/tenofovir disoproxil°# Dolutegravir/rilpivirine Doravirine/islatravir Doravirine/lamivudine/tenofovir disoproxil Efavirenz/emtricitabine/tenofovir disoproxil# Efavirenz/lamivudine/tenofovir disoproxil# Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil Emtricitabine/tenofovir alafenamide Emtricitabine/rilpivirine/tenofovir alafenamide Emtricitabine/rilpivirine/tenofovir disoproxil Emtricitabine/tenofovir disoproxil# Lamivudine/nevirapine/stavudine Lamivudine/nevirapine/zidovudine Lamivudine/raltegravir Lamivudine/tenofovir disoproxil# Lamivudine/zidovudine# Lopinavir/ritonavir# Pharmacokinetic boosters Cobicistat (c) Ritonavir (r)# Experimental agents Uncoating inhibitors TRIM5alpha (gene) Transcription inhibitors Tat antagonists Translation inhibitors Trichosanthin BNAbs Elipovimab Other Abzyme BIT225† Calanolide A Ceragenin Cyanovirin-N Diarylpyrimidines Epigallocatechin gallate (EGCG) Foscarnet Fosdevirine† Griffithsin Hydroxycarbamide KP-1461† Miltefosine North-methanocarbathymidine Portmanteau inhibitors Scytovirin Seliciclib† Synergistic enhancers Tre recombinase Zinc finger protein transcription factor Failed agents Aplaviroc Atevirdine Brecanavir Capravirine Dexelvucitabine Droxinavir Lasinavir Emivirine Lersivirine Lodenosine Loviride Mozenavir Palinavir Telinavir #WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III °DHHS recommended initial regimen options. ◊Formerly or rarely used agent.

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Adapted from the Wikipedia article [Saquinavir](https://en.wikipedia.org/wiki/Saquinavir) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Saquinavir?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.