Introduction
Primaquine is a drug used to treat and prevent Pneumocystis pneumonia and malaria. It is specifically used for treating malaria caused by Plasmodium vivax and Plasmodium ovale combined with other drugs and for prevention if other options are unavailable. Along with clindamycin, it serves as an alternate therapy for Pneumocystis pneumonia.
It is consumed orally. Stomach cramps, nausea, and vomiting are typical side effects. In addition, people who lack glucose-6-phosphate dehydrogenase (G6PD) should not take primaquine since it increases the risk of red blood cell disintegration. Therefore, primaquine use is frequently discouraged during pregnancy. However, it may be used while breastfeeding if the baby is known not to have a G6PD deficiency.
The only widely accessible anti-malarial that works effectively against gametocytes in malaria and avoids relapse in vivax and ovale malaria is primaquine. The importance of primaquine rises as malaria-endemic nations work towards eradication. Despite being strongly advised, it is frequently not administered to malaria patients due to hemolytic toxicity (damage of red blood cells due to the invasion of bacteria or virus) in individuals who lack glucose-6-phosphate dehydrogenase (G6PD) (gene frequency typically 3–30 % in malaria-endemic areas; >180 unique genetic variations). There have been 14 recorded fatalities from the usage of primaquine in 200 million persons over six decades.
What Is the History Associated With Primaquine?
The different eras where primaquine was put in use:
-
Primaquine was initially employed widely during the Korean War. Then, 14-day radical curative regimens were administered to over 250,000 US soldiers to eliminate long-latency P. vivax infections. Primaquine has been widely used since the 1950s to prevent seasonal long-latency P. vivax, but it is still unclear how many exposures have occurred.
-
Around 28 million people in the Chinese province of Jiangsu got mass preventive radical treatment regimens in the 1970s. This raises the possibility that up to 100 million people were treated nationwide.
-
Primaquine was administered to eight million individuals in Azerbaijan, Tajikistan, Northern Afghanistan, and North Korea (DPR Korea) to prevent or treat P. vivax infections. The population was watched for negative side effects during these treatments. To control and eradicate vivax and falciparum malaria in Nicaragua, 1.9 million people got a three-day chloroquine and primaquine regimen.
It is still being determined how many people have received the drastic 5 to 14-day primaquine regimens that have been frequently advised for more than 50 years in tropical areas where P. vivax is common. Over three million malaria cases have been documented annually since the revival of the disease in India in the early 1970s, which carries most of the burden of vivax malaria globally.
What Is Primaquine Toxicity?
Primaquine is a highly effective anti-malarial medication that is underutilized. Its use has been severely constrained and is still constrained by worries about potentially harmful hemolytic toxicity and the lack of a quick test to identify those at risk. All malaria patients receive primaquine treatment in addition to hemolysis, as do all G6PD-deficient patients. The deficiency's dose, duration, and severity affect how much hemolysis occurs.
A single low dose is certainly safe, but daily primate dosing for the radical treatment of vivax malaria in a patient with severe insufficiency carries the danger of potentially fatal hemolysis. Yet over the past 60 years, just 12 cases of acute hemolysis have been recorded. Although millions of people had such regimens in MDAs without documented fatalities, hundreds must have had severe G6PD deficiency. The simple fact that MDA patients who suddenly felt ill and had dark urine quit taking primaquine was the most likely cause of the problem.
The primaquine dosage is constrained by stomach pain at doses over 1 mg/kg. Primaquine is often well tolerated when administered with food at 0.5 mg base/kg. Although frequent, methemoglobinemia (a state where the blood transports less oxygen than is typical) is rarely harmful. Oxidant hemolysis is primaquine's principal side effect.
Normal participants may also experience some red cell loss, but G6PD-deficient patients are more susceptible. The usage of primaquine has been constrained because of the possibility of toxicity in G6PD deficiency. More than 180 distinct genetic G6PD variations exist, almost all of which bestow an unstable enzyme that degrades more quickly than the typical variant and leaves older red blood cells susceptible to oxidative damage. The adverse effects are mentioned below:
Deaths
Over the past six decades, only 14 deaths attributed to primaquine have been documented, of which 12 were caused by acute hemolysis. The widespread treatments in various regions worldwide were reported to have had hemolytic side effects but no fatalities. Although hemolysis was not screened for during these MDAs, it was anticipated. Therefore, information was given, and medical services were emphasized. However, concerns regarding the generalizability of this estimate are raised by the fact that the reported deaths primarily occurred in nations with a small proportion of the world's malaria burden.
Severe Adverse Event
Serious intravascular hemolysis accompanied by dark or black urine and moderate jaundice is primaquine's most frequent severe adverse event (SAE). Rare reports of allergic reactions and neuropsychiatric symptoms concerning primaquine use have been documented. Severe hemolysis (rupture of red blood cells) can have two dangerous side effects: hemoglobinuria, renal failure, and life-threatening anemia.
Hemolysis Due to Single-Dose Primaquine
Hemolysis is self-limiting due to the quick elimination of primaquine. This is taken advantage of in the interrupted MDA regimens (regardless of disease status, MDA is a campaign-style method utilized to administer medications to at-risk persons in a specific area) and the once-weekly 0.75-mg base/kg radical cure regimen advised for individuals with vivax malaria and "mild" G6PD mutations. Following each dose, reticulocytosis counteracts hemolysis, and the population of younger red blood cells grows more resistant to primaquine's hemolytic effects.
What Are the Common Adverse Effects of Primaquine?
The following are the adverse effects of primaquine:
-
Primaquine produces methemoglobinemia, a condition in which the blood contains less oxygen than it should, in people with cytochrome b5 reductase deficiency.
-
Overdosing can cause methemoglobinemia, loss of white blood cells, and loss of red blood cells, among other types of blood cell function reductions.
-
Primaquine may cause hemolytic anemia in people with glucose-6-phosphate dehydrogenase deficiency (G6PD).
Conclusion
Precipitation of hemolysis in G6PD deficient people is the most dreaded side effect of taking primaquine. Unfortunately, those not G6PD impaired may also experience clinically insignificant hemolysis from primaquine.
