Side Effects of primaquine: A Synthesis of Findings from 25 Studies

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Original Abstract of the Article

Main Research Findings

Primaquine is a medication used to treat malaria, particularly *Plasmodium vivax* and *Plasmodium ovale*. It's effective against various stages of the parasite, including the late hepatic stages and latent tissue forms. 4 . This makes it crucial for preventing relapses of *P. vivax* infection. 11 . However, primaquine's use is associated with side effects. Research has been conducted to develop new 5-aryl-8-aminoquinoline derivatives with potentially less toxicity compared to primaquine. 10 .

Reasons for Side Effects

Primaquine's side effects are primarily linked to its metabolism. 13 The drug undergoes biotransformation, producing various metabolites that can affect different tissues. For example, some metabolites might interact with red blood cells, contributing to hemolysis. 13 Additionally, primaquine's side effects can be amplified in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetic condition affecting red blood cell function. 9

Common Side Effects

Gastrointestinal

Primaquine can cause gastrointestinal side effects like nausea, vomiting, and abdominal pain. 19 11 5

Blood

Primaquine can impact blood health, potentially leading to methemoglobinemia and hemolytic anemia. 12 1 17 These effects are intensified in individuals with G6PD deficiency.

Skin

Skin reactions like itching can occur with primaquine use. 23 16

Others

Primaquine may also cause side effects like headache, dizziness, and vision problems. 24

Side Effect Management

Gastrointestinal

Consult a doctor if gastrointestinal issues arise during primaquine treatment. They may adjust the medication or dosage to manage the symptoms. 5

Blood

It's essential to undergo G6PD deficiency testing before starting primaquine treatment. 9 3 If G6PD deficiency is confirmed, the doctor may choose to avoid primaquine or adjust the dosage. 5

Skin

If skin reactions occur, seek medical advice. Medication changes or dosage adjustments might be necessary to alleviate the symptoms. 16

Others

Report any unusual symptoms to a doctor immediately during primaquine therapy.

Comparison Across Studies

Commonalities

Multiple studies consistently show that primaquine is effective against malaria but can also cause side effects.

Differences

The severity and type of side effects can vary across studies. These differences might stem from factors like the specific malaria parasite involved, research methodologies, and the health status of participants.

Considerations for Real-Life Application

Primaquine is a prescription medication for malaria treatment and should not be taken without a doctor's advice. Seek medical attention immediately if experiencing malaria symptoms. Also, remember that primaquine can pose a higher risk to individuals with G6PD deficiency. It's crucial to undergo G6PD testing before starting primaquine treatment.

Limitations of Current Research

Further research on primaquine's side effects is still needed. Specifically, we lack sufficient data on the long-term consequences of primaquine use and its impact on individuals with G6PD deficiency.

Future Research Directions

More research is needed to understand the full range of primaquine's side effects, especially long-term effects and its interaction with G6PD deficiency. Additionally, developing safer alternative medications for malaria treatment is crucial.

Conclusion

Primaquine is a valuable tool in malaria treatment, but its use is accompanied by potential side effects. Individuals with G6PD deficiency are at a heightened risk for severe side effects. When taking primaquine, consult with a doctor and strictly follow their instructions.

Literature analysis of 25 papers
Positive Content
16
Neutral Content
0
Negative Content
9
Article Type
0
0
0
4
22
1.

Artemisinin-based combination therapy successfully treated two hyperparasitaemic Plasmodium falciparum cases.

Author: MukhiBenudhar, GuptaHimanshu, PunnathKishore, AnvikarAnupkumar R, SrivastavaBina, GhoshSusanta Kumar

Successful treatment
Hyperparasitaemia

This study reports two hyperparasitaemic patients with Plasmodium falciparum malaria who successfully recovered with oral artemisinin-based combination therapy (ACT) and a single dose of primaquine. Hyperparasitaemia is an important event in severe malaria, and its presence may hinder malaria elimination efforts.

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

2.

Challenges for achieving safe and effective radical cure of Plasmodium vivax: a round table discussion of the APMEN Vivax Working Group.

Author: ThriemerKamala, LeyBenedikt, BobogareAlbino, DysoleyLek, AlamMohammad Shafiul, PasaribuAyodhia P, SattabongkotJetsumon, JambertElodie, DomingoGonzalo J, CommonsRobert, AuburnSarah, MarfurtJutta, DevineAngela, AktaruzzamanMohammad M, SohelNayeem, NamgayRinzin, DrukpaTobgyel, SharmaSurender Nath, SarawatiElvieda, SamadIriani, TheodoraMinerva, NambanyaSimone, OunekhamSonesay, MudinRose Nanti Binti, Da ThakurGarib, MakitaLeo Sora, DerayRaffy, LeeSang-Eun, BoazLeonard, DanansuriyaManjula N, MudiyanselageSantha D, ChinanonwaitNipon, KitchakarnSuravadee, NausienJohnny, NaketEsau, DucThang Ngo, Do ManhHa, HongYoung S, ChengQin, RichardsJack S, KusriastutiRita, SatyagrahaAri, NoviyantiRintis, DingXavier C, KhanWasif Ali, Swe PhruChing, GuodingZhu, QiGao, KanekoAkira, MiottoOlivo, NguitragoolWang, RoobsoongWanlapa, BattleKatherine, HowesRosalind E, Roca-FeltrerArantxa, DuparcStephan, BhowmickIpsita Pal, KenangalemEnny, BibitJo-Anne, BarryAlyssa, SintasathDavid, AbeyasingheRabindra, SibleyCarol H, McCarthyJames, von SeidleinLorenz, BairdJ Kevin, PriceRic N

Malaria Elimination
G6PD Deficiency

This meeting report summarizes the key discussion points from a round table discussion on the programmatic issues hindering the widespread use of primaquine (PQ) for radical cure of Plasmodium vivax malaria. The discussion highlighted the need for robust point-of-care (PoC) glucose-6-phosphate dehydrogenase (G6PD) tests and strategies to improve adherence to PQ regimens.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report.

Author: von SeidleinLorenz, AuburnSarah, EspinoFe, ShanksDennis, ChengQin, McCarthyJames, BairdKevin, MoyesCatherine, HowesRosalind, MénardDidier, BanconeGermana, Winasti-SatyahrahaAri, VestergaardLasse S, GreenJustin, DomingoGonzalo, YeungShunmay, PriceRic

Malaria control
Malaria elimination
Haemolysis

This article discusses the importance of diagnosing and managing glucose-6-phosphate dehydrogenase (G6PD) deficiency for safe and effective use of 8-aminoquinolines in malaria control and elimination. G6PD deficiency can lead to severe hemolysis when individuals are exposed to 8-aminoquinolines like primaquine. However, excluding people with unconfirmed G6PD deficiency limits the impact of these drugs. This article highlights the need for improved diagnosis of G6PD deficiency to facilitate broader use of 8-aminoquinolines.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Liver injury in children: signal analysis of suspected drugs based on the food and drug administration adverse event reporting system.

Author: LiuYan, LiHailong, HuangLiang, WanChaomin, WangHuiqing, JiaoXuefeng, ZengLinan, JiaZhijun, ChengGuo, ZhangLei, ZhangWei, ZhangLingli

Liver injury

This study analyzed 14,143 pediatric cases of hepatic adverse events (HAEs) reported to the FDA. 264 disproportionate drug signals were identified, with paracetamol, methotrexate, vincristine, valproic acid, and cyclophosphamide being the most commonly reported. Six new drug signals were identified: acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine.

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

8.

Caspofungin as Salvage Therapy for Pneumocystis Pneumonia in a Heart Transplant Recipient.

Author: AbolghasemiSara, Sharif-KashaniBabak, NaghashzadehFarah, MarjaniMajid, MoniriAfshin, DoroudiniaAtousa, TabarsiPayam

PCP treatment

This case report describes a patient with Pneumocystis pneumonia (PCP) who was successfully treated with a combination of trimethoprim-sulfamethoxazole, primaquine, and caspofungin. This treatment approach was effective despite the patient's history of renal failure.

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.

Language : English

9.

Prevalence and molecular basis of glucose-6-phosphate dehydrogenase deficiency in Afghan populations: implications for treatment policy in the region.

Author: LeslieToby, MoizBushra, MohammadNader, AmanzaiOmar, Ur RasheedHaroon, JanSakhi, SiddiqiAbdul M, NasirAmna, BegMohammad A, VinkMartijn

Malaria control
Malaria treatment
G6PD deficiency

This study assessed the prevalence and genotype of glucose-6-phosphate dehydrogenase deficiency (G6PD) in Afghanistan and examined the need for routine G6PD testing for malaria treatment and control.

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

10.

Antimalarial activity of novel 5-aryl-8-aminoquinoline derivatives.

Author: ShirakiHiroaki, KozarMichael P, MelendezVictor, HudsonThomas H, OhrtColin, MagillAlan J, LinAi J

Antimalarial activity
Hemolysis

This study explored the antimalarial activity and toxicity of a series of 5-aryl-8-aminoquinoline derivatives, aiming to separate antimalarial effects from hemolytic side effects. Several compounds showed promising antimalarial activity with reduced toxicity compared to existing drugs.

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

11.

Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline.

Author: SchwartzE, Regev-YochayG

Malaria prophylaxis
Gastrointestinal symptoms

Primaquine was found to be a safe and effective prophylactic drug against both P. falciparum and P. vivax malaria in travelers, with only 5.7% of those receiving primaquine developing malaria compared to 53% of those receiving doxycycline and 52% of those receiving mefloquine.

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

13.

Biotransformation of primaquine in vitro with human K562 and bone marrow cells.

Author: FrischerH, AhmadT, NoraM V, CarsonP E, SivarajanM, MellovitzR, PtakL, ParkhurstG W, ChowH S, KaizerH

Hemolysis
Methemoglobinemia

Primaquine metabolism can be studied in vitro using human erythroleukemic K562 cells. The study demonstrated that primaquine is metabolized into carboxyprimaquine in vitro and that this process can be blocked by BCNU.

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

14.

Safety of antimalarial medications for use while scuba diving in malaria Endemic Regions.

Author: PetersenKyle, RegisDavid P

Malaria prevention
Diving related illnesses

The safety and efficacy of antimalarials for travelers in a hyperbaric environment is unknown. More research is needed to evaluate the potential for adverse effects that could mimic or increase the risk of diving-related illnesses.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

The clinical importance of pharmacogenetics.

Author:

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

Language : English

17.

Primaquine overdose in a toddler.

Author: ViscloskyTimothy, SchaefferWilliam, PomeranzElaine, PonceDaphne Morrison

Hemolytic anemia
Methemoglobinemia

This case report describes a toddler with an accidental primaquine overdose and undiagnosed glucose-6-phosphate dehydrogenase (G6PD) deficiency. The patient developed severe methemoglobinemia and hemolytic anemia, highlighting the potential risks of primaquine in individuals with G6PD deficiency. This case emphasizes the importance of recognizing and managing these complications effectively.

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.

Language : English

18.

The use of a three compartment in vitro model to investigate the role of hepatic drug metabolism in drug-induced blood dyscrasias.

Author: TingleM D, ParkB K

Haemotoxicity

Dapsone metabolism by liver microsomes resulted in red blood cell toxicity, but not mononuclear leucocyte (MNL) toxicity. The presence of red blood cells protected MNL from toxicity. Synthetic dapsone hydroxylamine induced significant MNL toxicity.

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.

[Recurrence problems with preventive primaquine treatment in patients with malaria].

Author: RønnA M, BygbjergI C

Gastrointestinal side effects
Haemolytic anaemia
Methaemoglobin formation

Primaquine resistance was observed in patients with P. vivax malaria. Relapses occurred despite standard primaquine dosages. Higher doses may be required but should be administered with caution due to potential for serious side effects.

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.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Danish

20.

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests.

Author: DomingoGonzalo J, SatyagrahaAri Winasti, AnvikarAnup, BairdKevin, BanconeGermana, BansilPooja, CarterNick, ChengQin, CulpepperJanice, EziefulaChi, FukudaMark, GreenJustin, HwangJimee, LacerdaMarcus, McGraySarah, MenardDidier, NostenFrancois, NuchprayoonIssarang, OoNwe Nwe, BualombaiPongwit, PumpraditWadchara, QianKun, RechtJudith, RocaArantxa, SatimaiWichai, SovannarothSiv, VestergaardLasse S, Von SeidleinLorenz

G6PD deficiency risk

This report discusses the challenges and recommendations for G6PD deficiency testing in support of radical cure of Plasmodium vivax infections.

CongressA conference or meeting where experts in a specific field gather. It provides opportunities for presentations, discussions, and networking, and serves as a place to share expertise and learn about the latest trends in the industry.

Language : English

22.

Primaquine-chloroquine prophylaxis against malaria in Southeast-Asian refugees entering South Australia.

Author: GrimmondT R, CameronA S

Effective malaria prophylaxis
Transient hemoglobinuria

Primaquine and chloroquine combination was effective in reducing malaria incidence in Southeast Asian refugees.

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

Language : English

23.

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

24.

Is primaquine useful and safe as true exo-erythrocytic merontocidal, hypnozoitocidal and gametocidal antimalarial drug?

Author: López-AntuñanoF J

Malaria treatment
Hemolytic effects
Methemoglobinemia

Primaquine, an antimalarial drug, is effective against P. vivax gametocytes and may prevent relapses. However, the drug's use is limited by its potential for hemolytic and methemoglobinemic side effects, especially in individuals with glucose-6-phosphate dehydrogenase deficiency.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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