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{{Short description|Pharmaceutical drug}}
{{Drugbox
{{Drugbox
| verifiedrevid = 464214288
| verifiedrevid = 464214288
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| legal_US = Rx-only
| legal_US = Rx-only
| legal_UK =
| legal_UK =
| routes_of_administration = By mouth
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = P01
| ATC_prefix = P01
| ATC_suffix = BA03
| ATC_suffix = BA03


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability = 96%<ref>{{cite journal |vauthors=Mihaly GW, Ward SA, Edwards G, etal | title = Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size | year = 1985 | journal = Br J Clin Pharmacol | volume = 19 | pages = 745&ndash;50 | pmid = 4027117 | issue = 6 | pmc = 1463857 | doi=10.1111/j.1365-2125.1985.tb02709.x}}</ref>
| bioavailability = 96%<ref>{{cite journal | vauthors = Mihaly GW, Ward SA, Edwards G, Nicholl DD, Orme ML, Breckenridge AM | title = Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size | journal = British Journal of Clinical Pharmacology | volume = 19 | issue = 6 | pages = 745–750 | date = June 1985 | pmid = 4027117 | pmc = 1463857 | doi = 10.1111/j.1365-2125.1985.tb02709.x }}</ref>
| metabolism = Liver
| metabolism = Liver
| elimination_half-life = 6 hours
| elimination_half-life = 6 hours
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| IUPAC_name = (''RS'')-''N''-(6-methoxyquinolin-8-yl)pentane-1,4-diamine
| IUPAC_name = (''RS'')-''N''-(6-methoxyquinolin-8-yl)pentane-1,4-diamine
| C=15 | H=21 | N=3 | O=1
| C=15 | H=21 | N=3 | O=1
| molecular_weight = 259.347
| smiles = O(c1cc(NC(C)CCCN)c2ncccc2c1)C
| smiles = O(c1cc(NC(C)CCCN)c2ncccc2c1)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
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}}
}}
<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Primaquine''' is a medication used to treat and prevent [[malaria]] and to treat [[Pneumocystis pneumonia|''Pneumocystis'' pneumonia]].<ref name=AHFS2016/> Specifically it is used for malaria due to ''[[Plasmodium vivax]]'' and ''[[Plasmodium ovale]]'' along with other medications and for prevention if other options cannot be used.<ref name=AHFS2016/> It is an alternative treatment for ''Pneumocystis'' pneumonia together with [[clindamycin]].<ref name=AHFS2016/><ref name=Vale2009rev>{{cite journal|last1=Vale|first1=Nuno|last2=Moreira|first2=Rui|last3=Gomes|first3=Paula|title=Primaquine revisited six decades after its discovery|journal=European Journal of Medicinal Chemistry|date=March 2009|volume=44|issue=3|pages=937–953|doi=10.1016/j.ejmech.2008.08.011|pmid=18930565|hdl=10216/82052 |hdl-access=free}}</ref> It is taken by mouth.<ref name=AHFS2016/>
'''Primaquine''' is a [[medication]] used to treat and prevent [[malaria]] and to treat [[Pneumocystis pneumonia|''Pneumocystis'' pneumonia]].<ref name=AHFS2016/> Specifically it is used for malaria due to ''[[Plasmodium vivax]]'' and ''[[Plasmodium ovale]]'' along with other medications and for prevention if other options cannot be used.<ref name=AHFS2016/> It is an alternative treatment for ''Pneumocystis'' pneumonia together with [[clindamycin]].<ref name=AHFS2016/><ref name=Vale2009rev>{{cite journal | vauthors = Vale N, Moreira R, Gomes P | title = Primaquine revisited six decades after its discovery | journal = European Journal of Medicinal Chemistry | volume = 44 | issue = 3 | pages = 937–953 | date = March 2009 | pmid = 18930565 | doi = 10.1016/j.ejmech.2008.08.011 | hdl-access = free | hdl = 10216/82052 }}</ref> It is taken [[Oral administration|by mouth]].<ref name=AHFS2016/>


<!-- Side effects and mechanism -->
<!-- Side effects and mechanism -->
Common side effects include [[nausea]], vomiting, and stomach cramps.<ref name=AHFS2016/><ref name=YellowBook2016>{{cite book|last1=Arguin|first1=Paul M.|last2=Tan|first2=Kathrine R.|editor1-last=Brunette|editor1-first=Gary W.|title=CDC Health Information for International Travel 2016 (Yellow Book)|date=2016|publisher=CDC and Oxford University Press|isbn=978-0-19-937915-6|chapter-url=http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/malaria#1939|chapter=Malaria - Chapter 3|url-status=live|archiveurl=https://web.archive.org/web/20160114185552/http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/malaria#1939|archivedate=2016-01-14}}</ref> Primaquine should not be given to people with [[Glucose-6-phosphate dehydrogenase deficiency|glucose-6-phosphate dehydrogenase (G6PD) deficiency]] due to the risk of [[hemolysis|red blood cell breakdown]].<ref name=YellowBook2016/> It is often recommended that primaquine not be used during [[pregnancy]].<ref name=Ric2015>{{cite book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=57}}</ref><ref name="Hill2006">{{Cite journal|last1=Hill|first1=D. R.|last2=Baird|first2=J. K.|last3=Parise|first3=M. E.|last4=Lewis|first4=L. S.|last5=Ryan|first5=E. T.|last6=Magill|first6=A. J.|year=2006|title=Primaquine: Report from CDC expert meeting on malaria chemoprophylaxis I|journal=The American Journal of Tropical Medicine and Hygiene|volume=75|issue=3|pages=402–15|pmid=16968913|url=http://www.ajtmh.org/content/75/3/402.long|url-status=live|archiveurl=https://web.archive.org/web/20140123071557/http://www.ajtmh.org/content/75/3/402.long|archivedate=2014-01-23|doi=10.4269/ajtmh.2006.75.402|doi-access=free}}</ref> It may be okay in [[breastfeeding]] when the baby is known not to have G6PD deficiency.<ref name="Hill2006"/> The mechanisms of action is not entirely clear but is believed to involve effects on the malaria parasites' [[DNA]].<ref name=AHFS2016/>
Common side effects include [[nausea]], vomiting, and stomach cramps.<ref name=AHFS2016/><ref name=YellowBook2016>{{cite book | vauthors = Arguin PM, Tan KR | veditors = Brunette GW |title=CDC Health Information for International Travel 2016 (Yellow Book)|date=2016|publisher=CDC and Oxford University Press|isbn=978-0-19-937915-6|chapter-url=http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/malaria#1939|chapter=Malaria - Chapter 3|url-status=live|archive-url=https://web.archive.org/web/20160114185552/http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/malaria#1939|archive-date=2016-01-14}}</ref> Primaquine should not be given to people with [[Glucose-6-phosphate dehydrogenase deficiency|glucose-6-phosphate dehydrogenase (G6PD) deficiency]] due to the risk of [[hemolysis|red blood cell breakdown]].<ref name=YellowBook2016/> It is often recommended that primaquine not be used during [[pregnancy]].<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=57}}</ref><ref name="Hill2006">{{cite journal | vauthors = Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ | title = Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I | journal = The American Journal of Tropical Medicine and Hygiene | volume = 75 | issue = 3 | pages = 402–415 | date = September 2006 | pmid = 16968913 | doi = 10.4269/ajtmh.2006.75.402 | url = http://www.ajtmh.org/content/75/3/402.long | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20140123071557/http://www.ajtmh.org/content/75/3/402.long | archive-date = 2014-01-23 }}</ref> It may be used while [[breastfeeding]] if the baby is known not to have G6PD deficiency.<ref name="Hill2006"/> The mechanisms of action is not entirely clear but is believed to involve effects on the malaria parasites' [[DNA]].<ref name=AHFS2016/>


<!-- Society and culture -->
<!-- Society and culture -->
Primaquine was first made in 1946.<ref name=Vale2009rev/> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]], the safest and most effective medicines needed in a [[health system]].<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> It is available as a [[Generic drug|generic medication]].<ref name=AHFS2016>{{cite web|title=Primaquine Phosphate|url=https://www.drugs.com/monograph/primaquine-phosphate.html|publisher=The American Society of Health-System Pharmacists|accessdate=2 December 2016|url-status=live|archiveurl=https://web.archive.org/web/20161220060718/https://www.drugs.com/monograph/primaquine-phosphate.html|archivedate=20 December 2016}}</ref>
Primaquine was first made in 1946.<ref name=Vale2009rev/> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<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> It is available as a [[Generic drug|generic medication]].<ref name=AHFS2016>{{cite web|title=Primaquine Phosphate|url=https://www.drugs.com/monograph/primaquine-phosphate.html|publisher=The American Society of Health-System Pharmacists|access-date=2 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220060718/https://www.drugs.com/monograph/primaquine-phosphate.html|archive-date=20 December 2016}}</ref>


==Medical uses==
==Medical uses==


===Malaria===
===Malaria===
Primaquine is primarily used to prevent relapse of malaria due to ''[[Plasmodium vivax]]'' and ''[[Plasmodium ovale]]''.<ref name=CDC2013>{{cite web|title=Treatment of Malaria (Guidelines For Clinicians)|url=https://www.cdc.gov/malaria/resources/pdf/clinicalguidance.pdf|publisher=CDC|date=July 2013|url-status=live|archiveurl=https://web.archive.org/web/20170829173925/https://www.cdc.gov/malaria/resources/pdf/clinicalguidance.pdf|archivedate=2017-08-29}}</ref> It eliminates [[Plasmodium#Life cycle|hypnozoites]], the dormant liver form of the parasite,<ref>{{cite journal|last1=Markus|first1=MB|title=Malaria: Origin of the Term "Hypnozoite"|journal=Journal of the History of Biology|date=2011|volume=44|issue=4|pages=781–786|doi=10.1007/s10739-010-9239-3|pmid=20665090|s2cid=1727294}}</ref> after the organisms have been cleared from the bloodstream.<ref name=CDC2013/> If primaquine is not administered to patients with proven ''P. vivax'' or ''P. ovale'' infection, a very high likelihood of relapse exists for weeks or months (sometimes years).<ref name=CDC2013/> Use in combination with [[quinine]] or [[chloroquine]] each of which is very effective at clearing ''P. vivax'' from blood, improves outcomes; they appear to also potentiate the action of primaquine.<ref name=Baird2003rev>{{cite journal |author=Baird JK, Rieckmann KH |title=Can primaquine therapy for vivax malaria be improved? |journal=Trends Parasitol. |volume=19 |issue=3 |pages=115–20 |date=March 2003 |pmid=12643993 |doi= 10.1016/S1471-4922(03)00005-9|url=http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1094&context=usnavyresearch}}</ref>
Primaquine is primarily used to prevent relapse of malaria due to ''[[Plasmodium vivax]]'' and ''[[Plasmodium ovale]]''.<ref name=CDC2013>{{cite web|title=Treatment of Malaria (Guidelines For Clinicians)|url=https://www.cdc.gov/malaria/resources/pdf/clinicalguidance.pdf|publisher=CDC|date=July 2013|url-status=live|archive-url=https://web.archive.org/web/20170829173925/https://www.cdc.gov/malaria/resources/pdf/clinicalguidance.pdf|archive-date=2017-08-29}}</ref> It eliminates [[Plasmodium#Life cycle|hypnozoites]], the dormant liver form of the parasite,<ref>{{cite journal | vauthors = Markus MB | title = Malaria: origin of the term "hypnozoite" | journal = Journal of the History of Biology | volume = 44 | issue = 4 | pages = 781–786 | date = 2011 | pmid = 20665090 | doi = 10.1007/s10739-010-9239-3 | s2cid = 1727294 }}</ref> after the organisms have been cleared from the bloodstream.<ref name=CDC2013/> If primaquine is not administered to patients with proven ''P. vivax'' or ''P. ovale'' infection, a very high likelihood of relapse exists for weeks or months (sometimes years).<ref name=CDC2013/> But it has been hypothesized that primaquine (and perhaps also the newer, related drug tafenoquine) might kill a proportion of non-circulating merozoites as well as hypnozoites, such as merozoites in bone marrow, thereby reducing the number of recrudescences (not only hypnozoite-mediated relapses) that take place.<ref>{{cite journal |last1=Markus |first1=MB. |title=Safety and efficacy of tafenoquine for Plasmodium vivax malaria prophylaxis and radical cure: overview and perspectives |journal=Therapeutics and Clinical Risk Management |date=2021 |volume=17 |pages=989–999 |doi=10.2147/TCRM.S269336 |pmid=34526770 |pmc=8435617 |doi-access=free }}</ref> Clarity in this regard is expected to be forthcoming soon.<ref>{{cite journal |last1=Markus |first1=MB |title=Putative contribution of 8-aminoquinolines to preventing recrudescence of malaria |journal=Tropical Medicine and Infectious Disease |date=2023 |volume=8 |issue=5 |page=278 |doi=10.3390/tropicalmed8050278 |pmid=37235326|pmc=10223033 |doi-access=free }}</ref> Use of primaquine in combination with [[quinine]] or [[chloroquine]] each of which is very effective at clearing ''P. vivax'' from blood, improves outcomes; they appear to also potentiate the action of primaquine.<ref name=Baird2003rev>{{cite journal | vauthors = Baird JK, Rieckmann KH | title = Can primaquine therapy for vivax malaria be improved? | journal = Trends in Parasitology | volume = 19 | issue = 3 | pages = 115–120 | date = March 2003 | pmid = 12643993 | doi = 10.1016/S1471-4922(03)00005-9 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1094&context=usnavyresearch }}</ref>


As of 2016, the US [[Centers for Disease Control and Prevention]] recommended the use of primaquine for primary prophylaxis prior to travel to areas with a high incidence of ''P. vivax'', and for terminal prophylaxis (anti-relapse therapy) after travel.<ref name=YellowBook2016/>
As of 2016, the US [[Centers for Disease Control and Prevention]] recommends the use of primaquine for primary prophylaxis prior to travel to areas with a high incidence of ''P. vivax'', and for terminal prophylaxis (anti-relapse therapy) after travel.<ref name=YellowBook2016/>


A single dose of primaquine has rapid and potent ability to kill gametocytes (stage V) of ''P. falciparum'' and ''P. vivax'' in blood; it also kills asexual trophozoites of ''P. vivax'' in blood, but not of ''P. falciparum''.<ref name=Baird2003rev/> Because of its action against gametocytes, the WHO recommends it for use in reducing transmission to control ''P. falciparum'' infections.<ref name=WHOtrans>{{cite book|title=Single dose primaquine as a gametocytocide in ''Plasmodium falciparum'' malaria|publisher=World Health Organization|location=Geneva, Switzerland|url=https://www.who.int/malaria/publications/atoz/who_pq_policy_recommendation/en/index.html|date=October 2012|accessdate=2 January 2014|url-status=live|archiveurl=https://web.archive.org/web/20140102193933/http://www.who.int/malaria/publications/atoz/who_pq_policy_recommendation/en/index.html|archivedate=2 January 2014}}</ref>
A single dose of primaquine has rapid and potent ability to kill gametocytes (stage V) of ''P. falciparum'' and ''P. vivax'' in blood; it also kills asexual trophozoites of ''P. vivax'' in blood, but not of ''P. falciparum''.<ref name=Baird2003rev/> Because of its action against gametocytes, the WHO recommends it for use in reducing transmission to control ''P. falciparum'' infections.<ref name=WHOtrans>{{cite book|title=Single dose primaquine as a gametocytocide in ''Plasmodium falciparum'' malaria|publisher=World Health Organization|location=Geneva, Switzerland|url=https://www.who.int/malaria/publications/atoz/who_pq_policy_recommendation/en/index.html|date=October 2012|access-date=2 January 2014|url-status=dead|archive-url=https://web.archive.org/web/20140102193933/http://www.who.int/malaria/publications/atoz/who_pq_policy_recommendation/en/index.html|archive-date=2 January 2014}}</ref>


===''Pneumocystis'' pneumonia===
===''Pneumocystis'' pneumonia===
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===Special populations===
===Special populations===
Primaquine has not been studied extensively in people 65 and older so it is not known if dosing should be adjusted for this population.<ref name=USlabel>{{cite web|title=Primaquine label|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf|publisher=FDA|accessdate=10 November 2016|date=November 2007|url-status=live|archiveurl=https://web.archive.org/web/20161110175038/http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf|archivedate=10 November 2016}}</ref>
Primaquine has not been studied extensively in people 65 and older so it is not known if dosing should be adjusted for this population.<ref name=USlabel>{{cite web|title=Primaquine label|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf|publisher=FDA|access-date=10 November 2016|date=November 2007|url-status=live|archive-url=https://web.archive.org/web/20161110175038/http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/008316s017lbl.pdf|archive-date=10 November 2016}}</ref>


Primaquine should not be administered to anyone with G6PD deficiency because a severe reaction can occur, resulting in [[hemolytic anemia]].<ref name=YellowBook2016/> However, the WHO has recommended that a single dose of primaquine (0.25&nbsp;mg/kg) is safe to give even in individuals with G6PD deficiency, for the purpose of preventing transmission of ''P. falciparum'' malaria.<ref name=WHOtrans/>
Primaquine should not be administered to anyone with G6PD deficiency because a severe reaction can occur, resulting in [[hemolytic anemia]].<ref name=YellowBook2016/> However, the WHO has recommended that a single dose of primaquine (0.25&nbsp;mg/kg) is safe to give even in individuals with G6PD deficiency, for the purpose of preventing transmission of ''P. falciparum'' malaria.<ref name=WHOtrans/>
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Primaquine overdose can cause a dangerous reduction in various blood cell counts, and therefore should be avoided in people at risk for [[agranulocytosis]], which include people with conditions such as [[rheumatoid arthritis]] and [[lupus erythematosus]], and those taking concurrent medications that also decrease blood cell counts.<ref name=USlabel/>
Primaquine overdose can cause a dangerous reduction in various blood cell counts, and therefore should be avoided in people at risk for [[agranulocytosis]], which include people with conditions such as [[rheumatoid arthritis]] and [[lupus erythematosus]], and those taking concurrent medications that also decrease blood cell counts.<ref name=USlabel/>

Hemolytic reactions (moderate to severe) may occur in individuals with G6PD deficiency and in individuals with a family or personal history of favism. Areas of high prevalence of G6PD deficiency are Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, and Oceania. People from these regions have a greater tendency to develop hemolytic anemia (due to a congenital deficiency of erythrocytic G6PD) while receiving primaquine and related drugs.<ref>{{Cite web|title=PRIMAQUINE - Food and Drug Administration|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/008316s023lbl.pdf}}</ref><ref>{{cite journal | vauthors = Brewer GJ, Zarafonetis CJ | title = The haemolytic effect of various regimens of primaquine with chloroquine in American Negroes with G6PD deficiency and the lack of an effect of various antimalarial suppressive agents on erythrocyte metabolism | journal = Bulletin of the World Health Organization | volume = 36 | issue = 2 | pages = 303–308 | date = 1967 | pmid = 4864652 | pmc = 2476383 }}</ref>


==Adverse reactions==
==Adverse reactions==
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Overdosing can reduce the number of function of various kinds of blood cells, including [[anemia|loss of red blood cells]], methemoglobinemia, and [[leukopenia|loss of white blood cells]].<ref name=USlabel/>
Overdosing can reduce the number of function of various kinds of blood cells, including [[anemia|loss of red blood cells]], methemoglobinemia, and [[leukopenia|loss of white blood cells]].<ref name=USlabel/>


Persons with [[glucose-6-phosphate dehydrogenase deficiency]] (G6PD) may develop hemolytic anemia from primaquine.<ref>{{cite book |last1=Keystone |first1=Jay S. |last2=Kozarsky |first2=Phyllis E. |last3=Connor |first3=Bradley A. |last4=Nothdurft |first4=Hans D. |last5=Mendelson |first5=Marc |last6=Leder |first6=Karin |title=Travel Medicine E-Book |date=2018 |publisher=Elsevier Health Sciences |isbn=9780323547710 |page=185 |url=https://books.google.com/books?id=M4d7DwAAQBAJ&pg=PA185 |language=en}}</ref>
Persons with [[glucose-6-phosphate dehydrogenase deficiency]] (G6PD) may develop hemolytic anemia from primaquine.<ref>{{cite book | vauthors = Keystone JS, Kozarsky PE, Connor BA, Nothdurft HD, Mendelson M, Leder K |title=Travel Medicine E-Book |date=2018 |publisher=Elsevier Health Sciences |isbn=9780323547710 |page=185 |url=https://books.google.com/books?id=M4d7DwAAQBAJ&pg=PA185 |language=en}}</ref>


== Pharmacology ==
== Pharmacology ==


=== Mechanism of action ===
=== Mechanism of action ===
Primaquine is lethal to ''P. vivax'' and ''P. ovale'' in the liver stage, and also to ''P. vivax'' in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood.<ref name="Hill2006" />
Primaquine is lethal to ''P. vivax'' and ''P. ovale'' in the liver stage, and also to ''P. vivax'' in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood.<ref name="Hill2006" /> Liver hypnozoites aside, primaquine can possibly eliminate ''P. vivax'' merozoites in bone marrow as a result of accumulation there of hydrogen peroxide.<ref>{{cite journal |last1=Markus |first1=Miles B. |title=Killing of Plasmodium vivax by primaquine and tafenoquine |journal=Trends in Parasitology |date=2019 |volume=35 |issue=11 |pages=857–859 |doi=10.1016/j.pt.2019.08.009 |pmid=31522991|s2cid=202582476 }}</ref>


=== Pharmacokinetics ===
=== Pharmacokinetics ===
Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity.<ref>Cuong BT, Binh VQ, Dai B, et al. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? British Journal of Clinical Pharmacology. 2006;61(6):682-689. doi:10.1111/j.1365-2125.2006.02601.x.</ref> In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein [[orosomucoid]]. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Renal excretion of the parent drug is less than 4%.<ref name="Hill2006" /><ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/primaquine#section=Mechanism-of-Action|title=PRIMAQUINE {{!}} C15H21N3O - PubChem|last=Pubchem|website=pubchem.ncbi.nlm.nih.gov|access-date=2016-11-09|url-status=live|archiveurl=https://web.archive.org/web/20161110105944/https://pubchem.ncbi.nlm.nih.gov/compound/primaquine#section=Mechanism-of-Action|archivedate=2016-11-10}}</ref>
Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity.<ref>Cuong BT, Binh VQ, Dai B, et al. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? British Journal of Clinical Pharmacology. 2006;61(6):682-689. doi:10.1111/j.1365-2125.2006.02601.x.</ref> In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein [[orosomucoid]]. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Renal excretion of the parent drug is less than 4%.<ref name="Hill2006" /><ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/primaquine#section=Mechanism-of-Action|title=PRIMAQUINE {{!}} C15H21N3O | work = PubChem | publisher = U.S. National Library of Medicine |access-date=2016-11-09|url-status=live|archive-url=https://web.archive.org/web/20161110105944/https://pubchem.ncbi.nlm.nih.gov/compound/primaquine#section=Mechanism-of-Action|archive-date=2016-11-10}}</ref>


==Chemistry==
== Chemistry ==
Primaquine is an analog of [[pamaquine]] which was the first drug of the [[8-aminoquinoline]] class; [[tafenoquine]] is another such drug.<ref name=Baird2003rev/>
Primaquine is an analog of [[pamaquine]] which was the first drug of the [[8-aminoquinoline]] class; [[tafenoquine]] is another such drug.<ref name=Baird2003rev/>


==History==
== History==
Primaquine was first made by [[Robert Elderfield]] of [[Columbia University]] in the 1940s as part of a coordinated effort led by the [[Office of Scientific Research and Development]] in World War II to develop anti-malarial drugs to protect and treat soldiers fighting in the Pacific theater.<ref name=Baird2003rev/><ref name="Edgcomb 1950">{{cite journal |vauthors=Edgcomb JH, Arnold J, Young EH, etal | year = 1950 | title = Primaquine, SN 13272, a new curative agent in vivax malaria; a preliminary report. | journal = Journal of the National Malaria Society | volume = 9 | issue = 4 | pages = 285&ndash;92 | pmid = 14804087}}</ref>
Primaquine was first made by [[Robert Elderfield]] of [[Columbia University]] in the 1940s as part of a coordinated effort led by the [[Office of Scientific Research and Development]] in World War II to develop anti-malarial drugs to protect and treat soldiers fighting in the Pacific theater.<ref name=Baird2003rev/><ref name="Edgcomb 1950">{{cite journal | vauthors = Edgcomb JH, Arnold J, Yount EH, Alving AS, Eichelberger L, Jeffery GM, Eyles D, Young MD | display-authors = 6 | title = Primaquine, SN 13272, a new curative agent in vivax malaria; a preliminary report | journal = Journal of the National Malaria Society | volume = 9 | issue = 4 | pages = 285–292 | date = December 1950 | pmid = 14804087 }}</ref>


==Society and culture==
==Society and culture==
It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]], the safest and most effective medicines needed in a [[health system]].<ref name="WHO21st" />
It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st" /><ref name="WHO22nd" />


== Names ==
It is a generic drug and is available under many brand names worldwide, including Jasoprim, Malirid, Neo-Quipenyl, Pimaquin, Pmq, Primachina, Primacin, Primaquina, Primaquine, Primaquine diphosphate, Primaquine Phosphate, and Remaquin.<ref name=brands>{{cite web|title=Primaquine brand names|url=https://www.drugs.com/international/primaquine.html|publisher=Drugs.com|accessdate=10 November 2016|url-status=live|archiveurl=https://web.archive.org/web/20161111062111/https://www.drugs.com/international/primaquine.html|archivedate=11 November 2016}}</ref>
It is a generic drug and is available under many brand names worldwide, including Jasoprim, Malirid, Neo-Quipenyl, Pimaquin, Pmq, Primachina, Primacin, Primaquina, Primaquine, Primaquine diphosphate, Primaquine Phosphate, and Remaquin.<ref name=brands>{{cite web|title=Primaquine brand names|url=https://www.drugs.com/international/primaquine.html|publisher=Drugs.com|access-date=10 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161111062111/https://www.drugs.com/international/primaquine.html|archive-date=11 November 2016}}</ref>


⚫
* SN-13272<ref name="Edgcomb 1950"/><ref>{{cite journal | vauthors = Alving AS, Arnold J, Hockwald RS, Clayman CB, Dern RJ, Beutler E, Flanagan CL | title = Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine | journal = The Journal of Laboratory and Clinical Medicine | volume = 46 | issue = 2 | pages = 301–306 | date = August 1955 | pmid = 13242948 }}</ref>
⚫
==Research ==

⚫
== Research ==
Primaquine has been studied in animal models of [[Chagas disease]] and was about four times as effective as the standard of care, [[nifurtimox]].<ref name=Vale2009rev/>
Primaquine has been studied in animal models of [[Chagas disease]] and was about four times as effective as the standard of care, [[nifurtimox]].<ref name=Vale2009rev/>


A clinical trial in 2022 demonstrated the efficacy of higher-dose primaquine in preventing relapse of ''P. vivax'' malaria.<ref>{{cite journal | vauthors = Chamma-Siqueira NN, Negreiros SC, Ballard SB, Farias S, Silva SP, Chenet SM, Santos EJ, Pereira de Sena LW, Póvoa da Costa F, Cardoso-Mello AG, Marchesini PB, Peterka CR, Viana GM, Macedo de Oliveira A | display-authors = 6 | title = Higher-Dose Primaquine to Prevent Relapse of ''Plasmodium vivax'' Malaria | journal = The New England Journal of Medicine | volume = 386 | issue = 13 | pages = 1244–1253 | date = March 2022 | pmid = 35353962 | doi = 10.1056/NEJMoa2104226 | pmc = 9132489 | s2cid = 247840931 }}</ref>
==Synonyms==
⚫
* SN-13272<ref name="Edgcomb 1950"/><ref>{{cite journal|authors=Alving AS, Arnold J, Hockwald RS, Clayman CB, Dern RJ, Beutler E, Flanagan CL|year=1955|title=Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine|journal=J Lab Clin Med|volume=46|issue=2|pages=301–6|pmid=13242948}}</ref>


==References==
== References ==
{{Reflist}}
{{Reflist}}


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{{Antimalarials|state=collapsed}}
{{Antimalarials|state=collapsed}}
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{{Portal bar|Medicine}}

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{{portal bar|Medicine}}


[[Category:Antimalarial agents]]
[[Category:Antimalarial agents]]
[[Category:CYP2D6 inhibitors]]
[[Category:Quinolines]]
[[Category:Quinolines]]
[[Category:Phenol ethers]]
[[Category:Phenol ethers]]

Latest revision as of 20:04, 16 December 2023

Primaquine
Clinical data
Other namesprimaquine phosphate
AHFS/Drugs.comMonograph
MedlinePlusa607037
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability96%[1]
MetabolismLiver
Elimination half-life6 hours
Identifiers
  • (RS)-N-(6-methoxyquinolin-8-yl)pentane-1,4-diamine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.807 Edit this at Wikidata
Chemical and physical data
FormulaC15H21N3O
Molar mass259.353 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • O(c1cc(NC(C)CCCN)c2ncccc2c1)C
  • InChI=1S/C15H21N3O/c1-11(5-3-7-16)18-14-10-13(19-2)9-12-6-4-8-17-15(12)14/h4,6,8-11,18H,3,5,7,16H2,1-2H3 checkY
  • Key:INDBQLZJXZLFIT-UHFFFAOYSA-N checkY
  (verify)

Primaquine is a medication used to treat and prevent malaria and to treat Pneumocystis pneumonia.[2] Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used.[2] It is an alternative treatment for Pneumocystis pneumonia together with clindamycin.[2][3] It is taken by mouth.[2]

Common side effects include nausea, vomiting, and stomach cramps.[2][4] Primaquine should not be given to people with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to the risk of red blood cell breakdown.[4] It is often recommended that primaquine not be used during pregnancy.[5][6] It may be used while breastfeeding if the baby is known not to have G6PD deficiency.[6] The mechanisms of action is not entirely clear but is believed to involve effects on the malaria parasites' DNA.[2]

Primaquine was first made in 1946.[3] It is on the World Health Organization's List of Essential Medicines.[7][8] It is available as a generic medication.[2]

Medical uses

[edit]

Malaria

[edit]

Primaquine is primarily used to prevent relapse of malaria due to Plasmodium vivax and Plasmodium ovale.[9] It eliminates hypnozoites, the dormant liver form of the parasite,[10] after the organisms have been cleared from the bloodstream.[9] If primaquine is not administered to patients with proven P. vivax or P. ovale infection, a very high likelihood of relapse exists for weeks or months (sometimes years).[9] But it has been hypothesized that primaquine (and perhaps also the newer, related drug tafenoquine) might kill a proportion of non-circulating merozoites as well as hypnozoites, such as merozoites in bone marrow, thereby reducing the number of recrudescences (not only hypnozoite-mediated relapses) that take place.[11] Clarity in this regard is expected to be forthcoming soon.[12] Use of primaquine in combination with quinine or chloroquine each of which is very effective at clearing P. vivax from blood, improves outcomes; they appear to also potentiate the action of primaquine.[13]

As of 2016, the US Centers for Disease Control and Prevention recommends the use of primaquine for primary prophylaxis prior to travel to areas with a high incidence of P. vivax, and for terminal prophylaxis (anti-relapse therapy) after travel.[4]

A single dose of primaquine has rapid and potent ability to kill gametocytes (stage V) of P. falciparum and P. vivax in blood; it also kills asexual trophozoites of P. vivax in blood, but not of P. falciparum.[13] Because of its action against gametocytes, the WHO recommends it for use in reducing transmission to control P. falciparum infections.[14]

Pneumocystis pneumonia

[edit]

Primaquine is also used in the treatment of Pneumocystis pneumonia (PCP), a fungal infection commonly occurring in people with AIDS and, more rarely, in those taking immunosuppressive drugs. To treat PCP effectively, it is usually combined with clindamycin.[3]

Special populations

[edit]

Primaquine has not been studied extensively in people 65 and older so it is not known if dosing should be adjusted for this population.[15]

Primaquine should not be administered to anyone with G6PD deficiency because a severe reaction can occur, resulting in hemolytic anemia.[4] However, the WHO has recommended that a single dose of primaquine (0.25 mg/kg) is safe to give even in individuals with G6PD deficiency, for the purpose of preventing transmission of P. falciparum malaria.[14]

Primaquine is contraindicated in pregnancy, because the glucose-6-phosphate dehydrogenase status of the fetus would be unknown.[4]

Primaquine overdose can cause a dangerous reduction in various blood cell counts, and therefore should be avoided in people at risk for agranulocytosis, which include people with conditions such as rheumatoid arthritis and lupus erythematosus, and those taking concurrent medications that also decrease blood cell counts.[15]

Hemolytic reactions (moderate to severe) may occur in individuals with G6PD deficiency and in individuals with a family or personal history of favism. Areas of high prevalence of G6PD deficiency are Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, and Oceania. People from these regions have a greater tendency to develop hemolytic anemia (due to a congenital deficiency of erythrocytic G6PD) while receiving primaquine and related drugs.[16][17]

Adverse reactions

[edit]

Common side effects of primaquine administration include nausea, vomiting, and stomach cramps.[4][15]

In persons with cytochrome b5 reductase deficiency, primaquine causes methemoglobinemia, a condition in which the blood carries less oxygen that it does normally.[15]

Overdosing can reduce the number of function of various kinds of blood cells, including loss of red blood cells, methemoglobinemia, and loss of white blood cells.[15]

Persons with glucose-6-phosphate dehydrogenase deficiency (G6PD) may develop hemolytic anemia from primaquine.[18]

Pharmacology

[edit]

Mechanism of action

[edit]

Primaquine is lethal to P. vivax and P. ovale in the liver stage, and also to P. vivax in the blood stage through its ability to do oxidative damage to the cell. However, the exact mechanism of action is not fully understood.[6] Liver hypnozoites aside, primaquine can possibly eliminate P. vivax merozoites in bone marrow as a result of accumulation there of hydrogen peroxide.[19]

Pharmacokinetics

[edit]

Primaquine is well-absorbed in the gut and extensively distributed in the body without accumulating in red blood cells. Administration of primaquine with food or grapefruit juice increases its oral bioavailibity.[20] In blood, about 20% of circulating primaquine is protein-bound, with preferential binding to the acute phase protein orosomucoid. With a half-life on the order of 6 hours, it is quickly metabolized by liver enzymes to carboxyprimaquine, which does not have anti-malarial activity. Renal excretion of the parent drug is less than 4%.[6][21]

Chemistry

[edit]

Primaquine is an analog of pamaquine which was the first drug of the 8-aminoquinoline class; tafenoquine is another such drug.[13]

History

[edit]

Primaquine was first made by Robert Elderfield of Columbia University in the 1940s as part of a coordinated effort led by the Office of Scientific Research and Development in World War II to develop anti-malarial drugs to protect and treat soldiers fighting in the Pacific theater.[13][22]

Society and culture

[edit]

It is on the World Health Organization's List of Essential Medicines.[7][8]

Names

[edit]

It is a generic drug and is available under many brand names worldwide, including Jasoprim, Malirid, Neo-Quipenyl, Pimaquin, Pmq, Primachina, Primacin, Primaquina, Primaquine, Primaquine diphosphate, Primaquine Phosphate, and Remaquin.[23]

Research

[edit]

Primaquine has been studied in animal models of Chagas disease and was about four times as effective as the standard of care, nifurtimox.[3]

A clinical trial in 2022 demonstrated the efficacy of higher-dose primaquine in preventing relapse of P. vivax malaria.[25]

References

[edit]
  1. ^ Mihaly GW, Ward SA, Edwards G, Nicholl DD, Orme ML, Breckenridge AM (June 1985). "Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size". British Journal of Clinical Pharmacology. 19 (6): 745–750. doi:10.1111/j.1365-2125.1985.tb02709.x. PMC 1463857. PMID 4027117.
  2. ^ a b c d e f g "Primaquine Phosphate". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 2 December 2016.
  3. ^ a b c d Vale N, Moreira R, Gomes P (March 2009). "Primaquine revisited six decades after its discovery". European Journal of Medicinal Chemistry. 44 (3): 937–953. doi:10.1016/j.ejmech.2008.08.011. hdl:10216/82052. PMID 18930565.
  4. ^ a b c d e f Arguin PM, Tan KR (2016). "Malaria - Chapter 3". In Brunette GW (ed.). CDC Health Information for International Travel 2016 (Yellow Book). CDC and Oxford University Press. ISBN 978-0-19-937915-6. Archived from the original on 2016-01-14.
  5. ^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 57. ISBN 9781284057560.
  6. ^ a b c d Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ (September 2006). "Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I". The American Journal of Tropical Medicine and Hygiene. 75 (3): 402–415. doi:10.4269/ajtmh.2006.75.402. PMID 16968913. Archived from the original on 2014-01-23.
  7. ^ a b World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. ^ a b World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  9. ^ a b c "Treatment of Malaria (Guidelines For Clinicians)" (PDF). CDC. July 2013. Archived (PDF) from the original on 2017-08-29.
  10. ^ Markus MB (2011). "Malaria: origin of the term "hypnozoite"". Journal of the History of Biology. 44 (4): 781–786. doi:10.1007/s10739-010-9239-3. PMID 20665090. S2CID 1727294.
  11. ^ Markus, MB. (2021). "Safety and efficacy of tafenoquine for Plasmodium vivax malaria prophylaxis and radical cure: overview and perspectives". Therapeutics and Clinical Risk Management. 17: 989–999. doi:10.2147/TCRM.S269336. PMC 8435617. PMID 34526770.
  12. ^ Markus, MB (2023). "Putative contribution of 8-aminoquinolines to preventing recrudescence of malaria". Tropical Medicine and Infectious Disease. 8 (5): 278. doi:10.3390/tropicalmed8050278. PMC 10223033. PMID 37235326.
  13. ^ a b c d Baird JK, Rieckmann KH (March 2003). "Can primaquine therapy for vivax malaria be improved?". Trends in Parasitology. 19 (3): 115–120. doi:10.1016/S1471-4922(03)00005-9. PMID 12643993.
  14. ^ a b Single dose primaquine as a gametocytocide in Plasmodium falciparum malaria. Geneva, Switzerland: World Health Organization. October 2012. Archived from the original on 2 January 2014. Retrieved 2 January 2014.
  15. ^ a b c d e "Primaquine label" (PDF). FDA. November 2007. Archived (PDF) from the original on 10 November 2016. Retrieved 10 November 2016.
  16. ^ "PRIMAQUINE - Food and Drug Administration" (PDF).
  17. ^ Brewer GJ, Zarafonetis CJ (1967). "The haemolytic effect of various regimens of primaquine with chloroquine in American Negroes with G6PD deficiency and the lack of an effect of various antimalarial suppressive agents on erythrocyte metabolism". Bulletin of the World Health Organization. 36 (2): 303–308. PMC 2476383. PMID 4864652.
  18. ^ Keystone JS, Kozarsky PE, Connor BA, Nothdurft HD, Mendelson M, Leder K (2018). Travel Medicine E-Book. Elsevier Health Sciences. p. 185. ISBN 9780323547710.
  19. ^ Markus, Miles B. (2019). "Killing of Plasmodium vivax by primaquine and tafenoquine". Trends in Parasitology. 35 (11): 857–859. doi:10.1016/j.pt.2019.08.009. PMID 31522991. S2CID 202582476.
  20. ^ Cuong BT, Binh VQ, Dai B, et al. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? British Journal of Clinical Pharmacology. 2006;61(6):682-689. doi:10.1111/j.1365-2125.2006.02601.x.
  21. ^ "PRIMAQUINE | C15H21N3O". PubChem. U.S. National Library of Medicine. Archived from the original on 2016-11-10. Retrieved 2016-11-09.
  22. ^ a b Edgcomb JH, Arnold J, Yount EH, Alving AS, Eichelberger L, Jeffery GM, et al. (December 1950). "Primaquine, SN 13272, a new curative agent in vivax malaria; a preliminary report". Journal of the National Malaria Society. 9 (4): 285–292. PMID 14804087.
  23. ^ "Primaquine brand names". Drugs.com. Archived from the original on 11 November 2016. Retrieved 10 November 2016.
  24. ^ Alving AS, Arnold J, Hockwald RS, Clayman CB, Dern RJ, Beutler E, Flanagan CL (August 1955). "Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine". The Journal of Laboratory and Clinical Medicine. 46 (2): 301–306. PMID 13242948.
  25. ^ Chamma-Siqueira NN, Negreiros SC, Ballard SB, Farias S, Silva SP, Chenet SM, et al. (March 2022). "Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria". The New England Journal of Medicine. 386 (13): 1244–1253. doi:10.1056/NEJMoa2104226. PMC 9132489. PMID 35353962. S2CID 247840931.
[edit]
  • "Primaquine". Drug Information Portal. U.S. National Library of Medicine.
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