Primaquine
Encyclopedia
Primaquine 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
.
or P. ovale
malaria. Once the parasite has been eliminated from the bloodstream, the remaining hypnozoites must be removed from the liver and this is done by administering a 14 day course of primaquine. This process is called a radical cure.
If primaquine is not administered to patients with proven P. vivax or P. ovale infection, there is a very high likelihood of relapse within weeks or months (sometimes years).
When attempting a radical cure, primaquine requires the presence of quinine
or chloroquine
in order to work. If primaquine is given alone, the cure rate is only 21%. It is not known if other antimalarials such as mefloquine
are likewise able to potentiate the effect of primaquine.
(CDC) in some instances.
(PCP), a 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
.
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 the M*A*S*H episode "The Red/White Blues", in which Lebanese
-American Max Klinger and Jewish-American Orderly Goldman 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. Dangerous levels of methemoglobinemia only occur in patients with glucose-6-phosphate dehydrogenase deficiency
.
because there can be a severe reaction with hemolytic anemia
. Primaquine is contraindicated in pregnancy, because the Glucose-6-phosphate dehydrogenase
status of the fœtus would be unknown. Primaquine should not be given to patients with NADH methemoglobin reductase deficiency.
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.
The 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. Primaquine is not licensed in the UK, but is available on a named-patient basis.
in 1944. Primaquine was licensed for use in the USA by the FDA
in 1952 and is available as a generic drug
from a variety of manufacturers.
Primaquine is not licensed for use in the United Kingdom
. It is available on a named patient
basis only from certain pharmaceutical providers. 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).PRIMARYL of (schwartz)available as a brand.
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
and Pneumocystis pneumonia
Pneumocystis pneumonia
Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...
. It is a member of the 8-aminoquinoline
8-Aminoquinoline
8-Aminoquinoline is a form of aminoquinoline with an amine at the 8-position of quinoline.The 8-aminoquinoline family of drugs contains three members, primaquine, tafenoquine and pamaquine and are used in the treatment of malaria...
group of drugs that includes tafenoquine
Tafenoquine
Tafenoquine is an 8-aminoquinoline drug manufactured by GlaxoSmithKline that is currently being investigated as a potential treatment for malaria, as well as for malaria prevention....
and pamaquine
Pamaquine
Pamaquine is an 8-aminoquinoline drug used for the treatment of malaria. It is closely related to primaquine.-Adverse effects:Like primaquine, pamaquine causes haemolytic anaemia in patients with G6PD deficiency...
.
Radical cure
Primaquine is mainly used to treat the P. vivaxPlasmodium vivax
Plasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of the four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the...
or P. ovale
Plasmodium ovale
Plasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
malaria. Once the parasite has been eliminated from the bloodstream, the remaining hypnozoites must be removed from the liver and this is done by administering a 14 day course of primaquine. This process is called a radical cure.
If primaquine is not administered to patients with proven P. vivax or P. ovale infection, there is a very high likelihood of relapse within weeks or months (sometimes years).
When attempting a radical cure, primaquine requires the presence of quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
or chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
in order to work. If primaquine is given alone, the cure rate is only 21%. It is not known if other antimalarials such as mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
are likewise able to potentiate the effect of primaquine.
Primary prophylaxis
Primaquine is not routinely used to prevent malaria in travelers, and is only used as such when no other alternatives are appropriate. Primaquine is the recommended prophylactic agent by the Centers for Disease Control and PreventionCenters for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) in some instances.
Pneumocystis pneumonia
Primaquine is also used in the treatment of Pneumocystis pneumoniaPneumocystis pneumonia
Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...
(PCP), a fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
infection commonly occurring in people with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
and, more rarely, in those taking immunosuppressive drug
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
s. To treat PCP effectively it is usually combined with clindamycin
Clindamycin
Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
.
Adverse reactions
Side effectAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s of primaquine administration include nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting and stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
cramps. Other known adverse effects that occasionally occur are headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, visual disturbances and intense itching. Primaquine has also been shown to cause hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
in people of African or Mediterranean descent; this was a plot point in the M*A*S*H episode "The Red/White Blues", in which Lebanese
Lebanon
Lebanon , officially the Republic of LebanonRepublic of Lebanon is the most common term used by Lebanese government agencies. The term Lebanese Republic, a literal translation of the official Arabic and French names that is not used in today's world. Arabic is the most common language spoken among...
-American Max Klinger and Jewish-American Orderly Goldman developed anemia while taking primaquine, confusing the doctors who thought it was only a possibility if he were of African descent.
Primaquine causes methemoglobinemia
Methemoglobinemia
Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin in the blood. Methemoglobin is an oxidized form of hemoglobin that has an increased affinity for oxygen, resulting in a reduced ability to release oxygen to tissues. The oxygen–hemoglobin...
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. Dangerous levels of methemoglobinemia only occur in patients with glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
.
Contraindications
Primaquine should not be administered to anyone with glucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
because there can be a severe reaction with hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
. Primaquine is contraindicated in pregnancy, because the Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
status of the fœtus would be unknown. Primaquine should not be given to patients with NADH methemoglobin reductase deficiency.
The packaging label states that primaqine should not be given to patients with systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
or rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, but the rationale behind this is questionable.
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 (note that older authorities quote 15 mg instead);
- Plasmodium ovale: 15 mg once daily for 14 days.
The FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
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. 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 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 StudyStateville Penitentiary Malaria Study
The Stateville Penitentiary malaria study was a controlled study of the effects of malaria on the prisoners of Stateville Penitentiary near Joliet, Illinois in the 1940s. The study was conducted by the Department of Medicine at the University of Chicago in conjunction with the United States Army...
in 1944. Primaquine was licensed for use in the USA by the FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
in 1952 and is available as a generic drug
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
from a variety of manufacturers.
Primaquine is not licensed for use in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
. It is available on a named patient
Named patient programs
Governments worldwide have created provisions for granting access to drugs prior to approval for patients who have exhausted all alternative treatment options and do not match clinical trial entry criteria...
basis only from certain pharmaceutical providers. 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).PRIMARYL of (schwartz)available as a brand.