Primaquine
1698504
225039422
2008-07-11T16:22:28Z
KC Panchal
3449833
/* Contraindications */ c/e
{{Drugbox|
|IUPAC_name = ''N''-(6-methoxyquinolin-8-yl)pentane-1,4-diamine
| image = Primaquine.svg
| CAS_number=90-34-6
| ATC_prefix=P01
| ATC_suffix=BA03
| PubChem=6135
| DrugBank=APRD00604
| C = 15 | H = 21 | N = 3 | O = 1
| molecular_weight = 259.347 g/mol
| bioavailability=96%<ref>{{cite journal | author=Mihaly GW, Ward SA, Edwards G, ''et al.'' | 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=745–50 | pmid=4027117}}</ref>
| metabolism = Liver
| elimination_half-life=6 hours
| excretion = ?
| pregnancy_category = ?
| legal_US = Rx-only
| legal_status = Unlicensed (UK)
| routes_of_administration= Oral
}}
'''Primaquine''' (or '''primaquine phosphate''') is a medication used in the treatment of [[malaria]] and [[Pneumocystis pneumonia]]. It is a member of the [[8-aminoquinoline]] group of drugs that includes [[tafenoquine]] and [[pamaquine]].
==Indications==
===Radical cure===
Primaquine is mainly used to treat the [[Plasmodium vivax|''P. vivax'']] or [[Plasmodium ovale|''P. ovale'']] malaria. Once the parasite has been eliminated from the bloodstream, the remaining [[hypnozoite]]s must be removed from the liver and this is done by administering a 14 day course of primaquine (called '''radical cure''').
If primaquine is not administered to patients with proven ''P. vivax'' or ''P. ovale'' infection, there is a very high likelihood relapse within weeks or months (sometimes years).
When attempting a radical cure, primaquine requires the presence of [[quinine]] or [[chloroquine]] in order to work.<ref>{{cite journal | author=Alving AS, Arnold J, Hockwald RS, ''et al.'' | title=Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine | year=1955 | journal=J Lab Clin Med | volume=46 | pages=301–6 | pmid=13242948}}</ref> If primaquine is given alone, the cure rate is only 21%. This is why primaquine should always be given with quinine or chloroquine. It is not known if other antimalarials such as [[mefloquine]] are likewise able to potentiate the effect of primaquine.
===Primary prophylaxis===
Primaquine is not routinely used to prevent malaria in travellers, and is only used as such when no other alternatives are appropriate.<ref name="Hill2006">{{cite journal | author=Hill DR, Baird JK, Parise ME, ''et al.'' | title=Primaquine: Report from CDC expert meeting on malaria chemoprophylaxis I | year=2006 | journal=Am J Trop Med Hyg | volume=75 | issue=3 | pages=402–15 | pmid=16968913}}</ref> It is not licensed for this use in the U.S. or UK.
===Terminal prophylaxis===
Primaquine is also sometimes used presumptively to prevent malaria in people who have gone to areas where ''P. vivax'' or ''P. ovale'' are endemic (called '''terminal prophylaxis'''), but this practise is not common outside of the U.S. and is controversial.
===''Pneumocystis'' pneumonia===
Primaquine is also used in the treatment of [[Pneumocystis pneumonia|''Pneumocystis'' pneumonia]], a [[fungus|fungal]] infection commonly occurring in people with [[AIDS]] and, more rarely, in those taking [[immunosuppressive drug]]s. To treat PCP effectively it is usually combined with [[clindamycin]].
==Adverse reactions==
[[Adverse drug reaction|Side effect]]s of primaquine administration include [[nausea]], vomiting, and [[stomach]] cramps. Other known adverse effects that occasionally occur are [[headache]], visual disturbances and intense [[itching]].
Primaquine has also been shown to cause [[Hemolytic anemia]] in people of African or Mediterranean descent; this was a plot point in an episode of ''[[M*A*S*H]]'', in which [[Lebanon|Lebanese]]-American [[Maxwell Klinger|Max Klinger]] developed anemia while taking primaquine, confusing the doctors who thought it was only a possibility if he were of African descent.
Primaquine causes [[methemoglobinemia]] in all patients who take it (levels of up to 18% are reported, normal level is <1%), but this seldom causes symptoms and is always self-limiting.<ref>{{cite journal | author=Clayman CB, Arnold J, Hockwold RS, ''et al.'' | title=Toxicity of primaquine in caucasians | year=1952 | journal=JAMA | volume=149 | pages=1563–68 }}</ref> Dangerous levels of methemoglobinemia only occur in patients with [[glucose-6-phosphate dehydrogenase deficiency]].<ref name="Cohen1968">{{cite journal | author=Cohen RJ, Sachs JR, Wicker DJ, Conrad ME. | year=1968 | title=Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam | journal=[[New England Journal of Medicine|N Engl J Med]] | volume=279 | pages=1127–31 | pmid=5686480}}</ref><ref name="Coleman1996">{{cite journal | author=Coleman MD, Coleman NA. | year=1996 | title=Drug-induced methaemoglobinaemia. Treatment issues | journal=Drug Saf | volume=14 | pages=394–405 | pmid=8828017}}</ref>
==Contraindications==
Primaquine should not be administered to anyone with [[Glucose-6-phosphate dehydrogenase]] [[Glucose-6-phosphate dehydrogenase deficiency|deficiency]] as there can be a severe reaction with [[hemolytic anemia]]. Primaquine is contraindicated in pregnancy, because the [[Glucose-6-phosphate dehydrogenase|G-6-PD]] status of the fetus would be unknown. Primaquine should not be given to patients with [[NADH methemoglobin reductase deficiency]].<ref name="Cohen1968"/><ref name="Coleman1996"/>
The packaging label states that primaqine should not be given to patients with [[systemic lupus erythematosus]] or [[rheumatoid arthritis]], but the rationale behind this is questionable.<ref name="Hill2006"/>
==Dosing==
Primaquine doses are always expressed as base, not as salt (15 mg base=26.3 mg phosphate salt).
===Radical cure===
* ''Plasmodium vivax:'' 30 mg once daily for 14 days<ref>{{cite journal | author=Baird JK, Hoffman SL. | title=Primaquine therapy for malaria | journal=Clin Infect Dis | year=2004 | volume=39 | pages=1336–45 | pmid=15494911 | doi=10.1086/424663 }}</ref> (note that older authorities quote 15 mg instead);
* ''Plasmodium ovale:'' 15 mg once daily for 14 days.
The [[Food and Drug Administration|FDA]] licensed dose in the U.S. is 15 mg once daily, but this is not the dose recommended by the CDC for ''P. vivax''; the FDA decision in 1952 to limit the primaquine dose to 15 mg was motivated by the fact that G-6-PD testing was not routinely available, 15 mg was known to be effective against the ''P. vivax'' strains found in Korea (in the US, the main use of primaquine at that time was to treat soldiers returning from war), and because 15 mg of primaquine is not likely to cause hemolysis in G-6-PD deficient patients.<ref name="Hill2006"/> Primaquine is not licensed in the UK, but is available on a named-patient basis.
===Primary prophylaxis===
The dose of primaquine in primary malaria prophylaxis is 30 mg once daily, starting the day before travel and continuing for 7 days after returning. It needs only to be given for seven days after returning because primaquine is active against liver [[schizonts]] (the [[exoerythrocytic]] stages) and is therefore a [[malaria prophylaxis#causal prophylaxis|causal prophylactic]]. In children, the dose is 0.6 mg/kg/day (the maximum daily dose is 30 mg).
==Manufacturing and availability==
Primaquine was first tested on humans during the [[Stateville Penitentiary Malaria Study]] in 1944. Primaquine was licensed for use in the US by the [[Food and Drug Administration|FDA]] in 1952 and is available as a generic drug from a variety of manufacturers.
Primaquine is not licensed for use in the UK. It is available on a named patient basis only from [[Durbin]] or [[IDIS]]. Primaquine tablets available in the UK contain 7.5 mg primaquine base (13.2 mg phosphate salt). Primaquine tablets available in the U.S. contain 15 mg base (26.3 mg phosphate salt).
==References==
<references/>
*[http://www.niaid.nih.gov/publications/malaria/glossary.htm National Institute of Health]
*[http://www.aegis.com/factshts/network/access/drugs/prim.html AIDS Education Global Information System]
==External links==
{{Antimalarials}}
[[Category:Antimalarial agents]]
[[Category:Quinolines]]
[[de:Primaquin]]
[[it:Primachina]]
[[pt:Primaquina]]