Effects of primaquine: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Primaquine has been shown to have various effects in the treatment and prevention of malaria. For instance, 10 suggests that primaquine sterilizes gametocytes, preventing the spread of the parasite. In addition, 5 indicates that primaquine can suppress malaria relapses and the effect is dependent on the CYP2D6 genotype. 18 suggests that primaquine can interact with other medications. For example, it can increase blood levels of imatinib, a cancer drug. Other research indicates that primaquine, in combination with ivermectin, 8 improves the lethal effects against mosquitoes. Further, 19 , 1 , 17 , 7 , 3 , 21 , 9 , 13 , 11 , 20 , 14 , 2 , 16 , 4 , 22 studies indicate that primaquine can be effective in combination with other therapies for malaria. However, primaquine can cause side effects. For example, 3 reports that primaquine can cause serious hemolysis. Additionally, 16 suggests that primaquine may induce oxidative stress in the brain, liver, and kidneys of rats. The safety and efficacy of primaquine can vary from person to person and depending on other medications taken. Therefore, it is crucial to consult with a doctor before taking primaquine.

Benefits and Risks

Benefits Summary

Primaquine is effective for the treatment and prevention of malaria. Notably, it can help to suppress relapses of malaria, 5 , 19 , 12 , 6 and it also has potential to reduce the spread of malaria by inhibiting parasite transmission. 10 Additionally, it can increase the efficacy of other medications. For instance, 8 demonstrates that combining primaquine with ivermectin increases the lethal effect against malaria-carrying mosquitoes. Moreover, 18 , 13 , 9 studies suggest that primaquine might enhance the effectiveness of certain cancer medications. These findings imply that primaquine can play a valuable role in malaria control.

Risks Summary

Primaquine can have negative side effects, including 3 , 20 , 16 serious hemolysis and oxidative stress. It can also interact with other medications. 18 Therefore, it is essential to consult with a doctor before taking primaquine and follow their instructions closely. Individuals with G6PD deficiency are at an increased risk of serious hemolysis when taking primaquine, so extra caution is necessary. 3

Comparison between studies

Commonalities among studies

Numerous studies indicate that primaquine is effective in treating and preventing malaria. Additionally, the potential for side effects associated with primaquine is a common theme across these studies. These studies suggest that primaquine can be a valuable tool in malaria control, but it is important to be mindful of its potential side effects.

Differences between studies

Studies have shown variations in the effects and side effects of primaquine. For example, the effectiveness of primaquine in suppressing malaria relapses is influenced by the CYP2D6 genotype, 5 . Additionally, the side effects of primaquine can differ based on individual factors and other medications being taken. 3 , 16

Consistency and Contradictions

While the research findings concerning the effects and side effects of primaquine are generally consistent, there are some contradictions. For example, 3 reports that primaquine can lead to serious hemolysis, but this is not mentioned in other studies. Further research is needed to fully understand the effects and side effects of primaquine.

Real-World Implications and Precautions

While primaquine is an effective drug for treating and preventing malaria, it is important to remember the associated risks. Those with G6PD deficiency should be particularly cautious as they are at a higher risk for serious hemolysis. 3 Always consult a physician before taking primaquine and adhere to their instructions carefully.

Limitations of Current Research

Current research on primaquine is lacking in some areas. In particular, studies on long-term effects and side effects are scarce. The effects and side effects of primaquine can vary depending on individual characteristics and other medications taken. Therefore, further research is crucial.

Future Directions

Future studies are needed to investigate the long-term effects and side effects of primaquine. Research should also focus on how individual factors and other medications influence the effects and side effects of primaquine. Developing methods to enhance the effectiveness of primaquine while minimizing risks is also a critical area for future research.

Conclusion

Primaquine is a valuable drug for treating and preventing malaria, but it comes with potential side effects. It is essential to discuss the use of primaquine with a doctor and follow their instructions carefully. Continued research on primaquine can pave the way for safer and more effective malaria control strategies.

Literature analysis of 22 papers
Positive Content
18
Neutral Content
2
Negative Content
2
Article Type
4
2
2
1
22
1.

[A study of artemether combined with primaquine in the treatment of falciparum malaria].

Author: HuangJ R, GaoY Q, ElieN

Effective malaria treatment
Mild side effects

Artemether combined with primaquine showed good therapeutic effects in treating falciparum malaria. Both oral and intramuscular administration of artemether combined with primaquine resulted in lower relapse rates compared to single artemether. All treatment groups experienced mild side effects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : Chinese

2.

Prophylactic efficacy of primaquine for preventing Plasmodium falciparum and Plasmodium vivax parasitaemia in travelers: A meta-analysis and systematic review.

Author: KolifarhoodGoodarz, RaeisiAhmad, RanjbarMansour, HaghdoustAli Akbar, SchapiraAllan, HashemiSaeed, Masoumi-AslHossein, Mozafar SaadatiHossein, AzimiSara, KhosraviNasim, KondrashinAnatoly

Malaria prophylaxis

This systematic review and meta-analysis evaluated the prophylactic effectiveness and toxicity of primaquine for malaria chemoprophylaxis. The authors found that primaquine has high prophylactic efficacy, but further research is needed to compare its effectiveness and toxicity with other malaria chemoprophylaxis regimens.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

3.

Primaquine-induced Severe Hemolysis in the Absence of Concomitant Malaria: Effects on G6PD Activity and Renal Function.

Author: DouglasNicholas M, PieraKim A, RumasebAngela, LeyBenedikt, AnsteyNicholas M, PriceRic N

Relapse prevention
Hemolysis
Renal tubular injury

This case report describes a young, G6PD-deficient Australian man who experienced severe hemolysis after receiving a total dose of 2.04 mg/kg of primaquine for malaria prophylaxis. The case highlights the importance of G6PD testing before primaquine use, even for prophylaxis, and the potential for renal tubular injury in severe primaquine-induced hemolysis. It also demonstrates the safety of using paracetamol in the context of severe oxidative hemolysis.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

Effects of CYP2D6 genotypes on Plasmodium vivax recurrence after primaquine treatment: A meta-analysis.

Author: ParkYoon-A, ParkKi Hyun, YoonHa Young, YeeJeong, GwakHye Sun

Genotype-based dosing
P. vivax recurrence prediction
CYP2D6 polymorphism
P. vivax recurrence

A meta-analysis of 9 studies on CYP2D6 polymorphisms and Plasmodium vivax recurrence found that patients with CYP2D6 poor metabolizers (PMs), intermediate metabolizers (IMs), or normal metabolizers slow (NM-Ss) had a 1.8-fold higher risk of P. vivax recurrence compared to those with normal metabolizers fast (NM-Fs), extensive metabolizers (EMs), or ultrarapid metabolizer (UMs).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

7.

Atovaquone, chloroquine, primaquine, quinine and tetracycline: antiproliferative effects of relevant antimalarials on Neospora caninum.

Author: PereiraLuiz Miguel, de LucaGabriela, AbichabkiNathália de Lima Martins, BrochiJade Cabestre Venancio, BaroniLuciana, Abreu-FilhoPéricles Gama, YatsudaAna Patrícia

Neosporosis treatment

This study investigates the effects of atovaquone, chloroquine, quinine, primaquine, and tetracycline on the proliferation of *Neospora caninum*, a parasite causing abortion in cattle. The repurposing of antimalarial drugs could lead to novel treatment options for neosporosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

Safety, Pharmacokinetics, and Mosquito-Lethal Effects of Ivermectin in Combination With Dihydroartemisinin-Piperaquine and Primaquine in Healthy Adult Thai Subjects.

Author: KobylinskiKevin C, JittamalaPodjanee, HanboonkunupakarnBorimas, PukrittayakameeSasithon, PantuwatanaKanchana, PhasomkusolsilSiriporn, DavidsonSilas A, WinterbergMarkus, HoglundRichard M, MukakaMavuto, van der PluijmRob W, DondorpArjen, DayNicholas P J, WhiteNicholas J, TarningJoel

Accelerate malaria elimination
Impaired liver function

This study evaluated the safety, tolerability, pharmacokinetics, and mosquito-lethal effects of combinations of ivermectin, dihydroartemisinin-piperaquine, and primaquine in humans. Coadministration of ivermectin and dihydroartemisinin-piperaquine increased ivermectin concentrations and mosquito-lethal effects. Ivermectin showed greater than predicted mosquito-lethal effects against major Southeast Asian malaria vectors. These findings suggest that combining ivermectin with antimalarial drugs could accelerate malaria elimination.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Insights into the mechanism of antiproliferative effects of primaquine-cinnamic acid conjugates on MCF-7 cells.

Author: MabetaPeace, PavićKristina, ZorcBranka

Apoptosis induction
Cancer cell inhibition
Metastasis inhibition

Primaquine-cinnamic acid conjugates 1 and 3 induced apoptosis in MCF-7 cells, inhibiting their migration and invasion, while compound 2 had a marginal effect.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Transmission-blocking Effects of Primaquine and Methylene Blue Suggest Plasmodium falciparum Gametocyte Sterilization Rather Than Effects on Sex Ratio.

Author: BradleyJohn, SoumaréHarouna M, MahamarAlmahamoudou, DiawaraHalimatou, RohMichelle, DelvesMichael, DrakeleyChris, ChurcherThomas S, DickoAlassane, GoslingRoly, BousemaTeun

Malaria transmission blocking

Gametocyte density and sex ratio predict the proportion of mosquitoes infected after feeding on blood of patients receiving nongametocytocidal drugs. Primaquine and methylene blue sterilize gametocytes before affecting their density and sex ratio, requiring mosquito feeding experiments to demonstrate their early transmission-blocking effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers.

Author: AriffinNorliza Mat, IslahudinFarida, KumolosasiEndang, Makmor-BakryMohd

Reduced P. vivax recurrence

This study investigated the influence of genetic polymorphisms in MAO-A, CYP2D6, CYP1A2, and CYP2C19 on primaquine metabolism, the drug used to prevent recurrent Plasmodium vivax malaria infections. The study found significant effects of polymorphisms in MAO-A, CYP2D6, and CYP2C19, suggesting that genetic testing could help personalize primaquine dosage and optimize P. vivax management.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum.

Author: WampflerRahel, HofmannNatalie E, KarlStephan, BetuelaInoni, KinboroBenson, LorryLina, SilkeyMariabeth, RobinsonLeanne J, MuellerIvo, FelgerIngrid

Malaria relapse prevention

Primaquine (PQ) is the only antimalarial that can prevent relapses of *Plasmodium vivax* malaria. This study showed that PQ treatment also clears mature *P. falciparum* gametocytes, which can reduce the transmission of malaria after treatment.

Clinical Trial, Phase IVPost-marketing surveillance. Monitors long-term safety/efficacy after approval.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

15.

Side Effects of Chloroquine and Primaquine and Symptom Reduction in Malaria Endemic Area (Mâncio Lima, Acre, Brazil).

Author: BragaCássio Braga E, MartinsAntonio Camargo, CayotopaAthaid David Escalante, KleinWagner Werner, SchlosserAndreus Roberto, da SilvaAline Ferreira, de SouzaMardelson Nery, AndradeBreno Wilson Benevides, Filgueira-JúniorJosé Alcântara, PintoWagner de Jesus, da Silva-NunesMônica

Reduces malaria symptoms
Gastrointestinal side effects

This study evaluated the side effects of chloroquine and primaquine in 50 patients with vivax malaria. While the drugs reduced systemic and algic symptoms, they also increased gastrointestinal symptoms and choluria, potentially leading to poor adherence to treatment. Other side effects reported included blurred vision, pruritus, paresthesia, insomnia, and skin "stings."

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

16.

Effects of primaquine and chloroquine on oxidative stress parameters in rats.

Author: GiovanellaFrancianne, FerreiraGabriela K, de PráSamira D T, Carvalho-SilvaMilena, GomesLara M, ScainiGiselli, GonçalvesRenata C, MichelsMonique, GalantLetícia S, LongarettiLuiza M, DajoriAna Luiza, AndradeVanessa M, Dal-PizzolFelipe, StreckEmilio L, de SouzaRenan P

Malaria treatment
DNA damage
Oxidative stress

Primaquine and chloroquine, antimalarial drugs, can induce oxidative stress and DNA damage in the brain, liver, and kidney of rats after prolonged treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Effects of the antimalarial drug primaquine on the dynamic structure of lipid model membranes.

Author: BassoLuis G M, RodriguesRenata Z, NaalRose M Z G, Costa-FilhoAntonio J

Membrane destabilization

Primaquine is a drug used to treat malaria. The drug interacts with lipid membranes, causing changes in membrane fluidity and acyl chain dynamics.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

[Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development].

Author: VásquezAna María, SanínFelipe, AlvarezLuís Gonzalo, TobónAlberto, RíosAlexandra, BlairSilvia

Malaria treatment

This study describes the implementation of an artesunate (AS)-mefloquine (MQ) treatment program for Plasmodium falciparum malaria in Antioquia, Colombia. The addition of primaquine (PQ) aimed to eliminate malaria gametocytes and reduce transmission.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : Spanish

20.

Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes.

Author: GanesanShobana, TekwaniBabu L, SahuRajnish, TripathiLalit M, WalkerLarry A

Malaria cure
Hemotoxicity
Oxidative stress

Primaquine, an antimalarial drug, can cause hemotoxicity, particularly in individuals with glucose-6-phosphate dehydrogenase deficiency. This study identifies cytochrome P450 (CYP) isoforms that contribute to primaquine hemotoxicity, providing insights for potentially minimizing these adverse effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

21.

Comparative mutagenic and genotoxic effects of three antimalarial drugs, chloroquine, primaquine and amodiaquine.

Author: ChatterjeeT, MuhkopadhyayA, KhanK A, GiriA K

Antimalarial drug genotoxicity

The study assessed the mutagenic and genotoxic effects of three antimalarial drugs: chloroquine, primaquine, and amodiaquine. All three drugs showed weak mutagenic effects in bacteria, but were genotoxic in mouse bone marrow cells.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine), quinine sulfate, mefloquine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii.

Author: HolfelsE, McAuleyJ, MackD, MilhousW K, McLeodR

Inhibition of Toxoplasma gondii

This study evaluated the in vitro effect of several antimicrobial agents on Toxoplasma gondii tachyzoites. Arteether and cycloguanil inhibited T. gondii in vitro.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

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