Side Effects of pyrazinamide: A Synthesis of Findings from 29 Studies

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Original Abstract of the Article

Main Research Findings

Pyrazinamide is one of the first-line drugs used in the treatment of tuberculosis. However, pyrazinamide is known to cause various side effects such as hepatotoxicity, rash, and arthralgia. 12 , 2 .

Pyrazinamide is metabolized and activated in the liver. This metabolic process can put a strain on the liver and cause hepatotoxicity. 23 . Pyrazinamide can also stimulate the immune system and cause allergic reactions such as rash and arthralgia. 19 .

Side effects of pyrazinamide are more likely to be seen in elderly people and those with a history of hepatitis. 12 . Pyrazinamide can also disrupt the balance of gut microbiota and impair the immune function of alveolar macrophages. 6 .

Reasons for Side Effects

Side effects of pyrazinamide are thought to be caused by the metabolic process in the liver and the effects on the immune system. 23 , 19 . Pyrazinamide can also disrupt the balance of gut microbiota and impair the immune function of alveolar macrophages. 6 .

Common Side Effects

Hepatotoxicity

Pyrazinamide is metabolized and activated in the liver. This metabolic process can put a strain on the liver and cause hepatotoxicity. 23 . Symptoms of hepatotoxicity include jaundice, loss of appetite, nausea, fatigue, etc. 2 . Hepatotoxicity can improve if pyrazinamide is discontinued. 12 .

Rash

Pyrazinamide can stimulate the immune system and cause allergic reactions such as rash. 19 . Rash can improve if pyrazinamide is discontinued. 12 .

Arthralgia

Pyrazinamide can stimulate the immune system and cause allergic reactions such as arthralgia. 19 . Arthralgia can improve if pyrazinamide is discontinued. 12 .

Other Side Effects

In addition to the above side effects, pyrazinamide can cause various side effects such as gastrointestinal symptoms (nausea, vomiting, loss of appetite), neurological symptoms (headache, dizziness, lightheadedness), blood abnormalities, etc. 12 , 13 .

Countermeasures for Side Effects

Hepatotoxicity

To prevent hepatotoxicity, it is important to monitor liver function regularly. 23 . If symptoms of hepatotoxicity appear, pyrazinamide should be discontinued and a doctor's instructions should be followed. 12 .

Rash

If a rash appears, pyrazinamide should be discontinued and a doctor's instructions should be followed. 12 . Rash can be treated with antihistamines or steroids.

Arthralgia

If arthralgia appears, pyrazinamide should be discontinued and a doctor's instructions should be followed. 12 . Arthralgia can be treated with analgesics or anti-inflammatories.

Other Side Effects

Pyrazinamide can cause various side effects. If you are concerned about side effects, please consult your doctor.

Comparison between Studies

Common Points of Studies

Many studies have confirmed that pyrazinamide causes side effects such as hepatotoxicity, rash, and arthralgia. 12 , 2 , 19 .

Differences in Studies

The incidence of side effects and the patient groups that are more likely to develop side effects vary across studies. 12 , 2 , 19 . For example, 12 shows that elderly people and those with a history of hepatitis are more likely to experience pyrazinamide side effects.

Precautions for Application in Daily Life

Pyrazinamide is an effective drug for treating tuberculosis, but it also carries the risk of side effects. 12 , 2 . When taking pyrazinamide, it is important to discuss side effects with your doctor and follow their instructions. 19 .

Limitations of Current Research

Research on the side effects of pyrazinamide is not yet sufficient. In particular, further research is needed on the effects of pyrazinamide on the gut microbiota. 6 .

Future Research Directions

The development of new treatments and preventive measures to reduce the side effects of pyrazinamide is needed. 23 . Research is also needed to elucidate the effects of pyrazinamide on the gut microbiota and evaluate the risk of side effects. 6 .

Conclusion

Pyrazinamide is an effective drug for treating tuberculosis, but it carries the risk of side effects such as hepatotoxicity, rash, and arthralgia. 12 , 2 . When taking pyrazinamide, it is important to discuss side effects with your doctor and follow their instructions. 19 .

Literature analysis of 29 papers
Positive Content
17
Neutral Content
1
Negative Content
11
Article Type
4
1
1
1
28
1.

Effectiveness and Safety of Short-term Regimen for Multidrug-resistant Tuberculosis Treatment: A Systematic Review of Cohort Studies.

Author: MahardaniPutu Nandika, WatiDyah Kanya, SiloamAzriel, SavitriNi Putu Ayu, ManggalaArya Krisna

Improved treatment success
Shorter treatment duration
Dysglycemia
Gastrointestinal problems
Liver problems
Ototoxicity

This systematic review examined the effectiveness and safety of short-term regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB). STRs showed higher success rates and shorter treatment durations than the 2011 WHO regimen, with gastrointestinal issues, ototoxicity, and liver problems being common side effects.

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

2.

The high incidence of severe adverse events due to pyrazinamide in elderly patients with tuberculosis.

Author: KwonByoung Soo, KimYoulim, LeeSang Hoon, LimSung Yoon, LeeYeon Joo, ParkJong Sun, ChoYoung-Jae, YoonHo Il, LeeChoon-Taek, LeeJae Ho

PZA
SAEs

Pyrazinamide (PZA) was the most common drug associated with serious adverse events (SAEs) among first-line anti-tuberculosis drugs. Older age was an independent risk factor for SAEs.

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

Language : English

3.

Mortality from adverse drug reaction-related hospitalizations in south-west Ethiopia: A cross-sectional study.

Author: AngamoM T, ChalmersL, CurtainC M, YilmaD, BereznickiL

Drug mortality

This study aimed to determine the mortality rate due to adverse drug reactions (ADRs) in a hospital in Ethiopia, identify the drugs involved, and explore contributing factors.

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

Language : English

5.

Potential drug-drug interactions associated with adverse clinical outcomes and abnormal laboratory findings in patients with malaria.

Author: NoorSidra, IsmailMohammad, KhadimFaiza

Drug-drug interactions

This study investigated the prevalence and clinical relevance of potential drug-drug interactions in hospitalized patients with malaria.

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

Language : English

6.

Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.

Author: KhanNargis, MendoncaLaura, DhariwalAchal, FontesGhislaine, MenziesDick, XiaJianguo, DivangahiMaziar, KingIrah L

Anti-TB drug side effects
Gut dysbiosis

Anti-tuberculosis therapy (ATT) can alter the gut microbiota, potentially impacting the immune response to Mycobacterium tuberculosis (Mtb). This study showed that INH and PYZ, two common ATT drugs, increased Mtb susceptibility in mice by impairing macrophage function. This highlights a potential consequence of ATT on the host's ability to fight TB.

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.

Prevention of hepatotoxicity due to anti tuberculosis treatment: a novel integrative approach.

Author: AdhvaryuMeghna R, ReddyNarsimha, VakhariaBhasker C

Hepatotoxicity prevention
TB treatment

A herbal formulation containing Curcuma longa and Tinospora cordifolia prevented anti-tuberculosis treatment induced hepatotoxicity and improved disease outcome and patient compliance.

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

9.

Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity.

Author: CocaNatalia Saldanha Magalhães, OliveiraMarcelo Silva, VoietaIzabela, AntunesCarlos Maurício de Figueiredo, LambertucciJosé Roberto

Hepatotoxicity

HIV infection may or may not be associated with rifampin, isoniazid, and pyrazinamide hepatotoxicity depending on the definition used. In a study of 162 patients with tuberculosis, the prevalence of hepatotoxicity varied depending on the definition used, with no significant difference between HIV-infected and uninfected patients when using more stringent definitions.

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.

[Treatment of tuberculosis. Current standards].

Author: SchabergT

High cure rate
Side effects

Drug-sensitive tuberculosis has a high cure rate (over 95%) with standard treatment, but drug-resistant tuberculosis requires expert management due to treatment complexities and side effects.

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.
Practice GuidelineGuidelines and recommendations for the diagnosis and treatment of specific medical conditions in medical practice.

Language : German

11.

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

Author: GaoJing-Tao, DuJuan, WuGui-Hui, PeiYi, GaoMeng-Qiu, MartinezLeonardo, FanLin, ChenWei, XieLi, ChenYu, WangHua, JinLong, LiGuo-Bao, ZongPei-Lan, XiongYu, WuQian-Hong, LiMing-Wu, YanXiao-Feng, MiaoYan-Fang, CaiQing-Shan, LiXin-Jie, BaiDa-Peng, GengShu-Jun, YangGuo-Li, TangPei-Jun, ZengYi, ChenXiao-Hong, LiTong-Xia, CaiCui, ZhouYun, ZhuoMa, WangJian-Yun, GuanWen-Long, XuLin, ShiJi-Chan, ShuWei, ChengLi-Li, TengFei, NingYu-Jia, XieShi-Heng, SunYu-Xian, ZhangLi-Jie, LiuYu-Hong

Drug safety monitoring
Drug side effects

This study will evaluate the frequency and severity of adverse events related to bedaquiline-containing regimens for drug-resistant tuberculosis in a cohort of Chinese patients.

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

Language : English

13.

[A severe side effect of antitubercular therapy: pyrazinamide induced thrombocytopenia].

Author: RoseauJ-B, BerardH, N'guyen Huy ThuyG, RocherF, LegodecJ, ChouaidC

Bleeding
Thrombocytopenia

This study highlights a rare but serious side effect of pyrazinamide, an antitubercular drug, which is thrombocytopenia (low platelet count). This side effect can lead to bleeding and requires careful monitoring, especially in patients receiving multiple medications.

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 : French

14.

Determination of antituberculosis drug concentration in human plasma by MALDI-TOF/TOF.

Author: NotariStefania, ManconeCarmine, SergiManuel, GullottaFrancesca, BevilacquaNazzario, TempestilliMassimo, UrsoRocco, LauriaFrancesco Nicola, PucilloLeopoldo Paolo, TripodiMarco, AscenziPaolo

TB drug monitoring

This study developed a method using MALDI-TOF/TOF mass spectrometry to measure four anti-tuberculosis drugs in patient plasma. It achieved a high recovery rate (87-110%) and low detection limits (0.08-0.15 pmol/µL).

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.
Validation StudyResearch to assess the validity and reliability of new measurement methods or diagnostic tests.

Language : English

16.

Case Report with Systematic Literature Review on Vascular Complications of BCG Intravesical Therapy for Bladder Cancer.

Author: KingBrianna, SinghDhanveer, RathoreAnimesh, FlennerRonald, FlemmerMark

Bladder cancer treatment
Aneurysm

This study reviewed literature and reported a new case of mycotic aneurysm potentially caused by BCG immunotherapy for bladder cancer. This suggests that vascular complications from BCG may be more common than previously thought, necessitating further research and the development of guidelines for diagnosis and management.

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

17.

Tuberculosis treatment incompletion in patients with lung cancer: occurrence and predictors.

Author: LeeChung-Shu, ShuChin-Chung, ChenYi-Chen, LiaoKuang-Ming, HoChung-Han

TB treatment incompletion

Treatment incompletion occurred in 61.13% of lung cancer patients with new-onset tuberculosis (TB). Advanced cancer stage and no first-line TB drug use were independent factors for treatment incompletion.

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

Language : English

18.

Anti‑tuberculosis drugs decrease viability and stimulate the expression of chondrocyte marker genes in human nucleus pulposus cells.

Author: LehmannTomasz P, GłowackiMaciej, MisterskaEwa, WalczakMichał, JagodzińskiPaweł P, GłowackiJakub

Decreased IVD cell viability
Side effects

Anti-tuberculosis drugs, including isoniazid, rifampicin, ethambutol, and pyrazinamide, can increase the expression of chondrocyte marker genes in intervertebral disc cells, potentially impacting disc health. Long-term use of INH and RIF can also decrease cell viability. However, these drugs did not affect glycosaminoglycan concentrations.

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 approach in a case of allergic reaction to antituberculosis drugs -- a case report].

Author: CostinMagda, TesloianuA, MihăescuT, ButnaruElena

Tuberculosis treatment
Allergic reaction

A 24-year-old woman experienced a severe allergic reaction, including a generalized rash and itch, after just 7 days of treatment for tuberculosis with isoniazid, rifampicin, ethambutol, and pyrazinamide. This case highlights the importance of training patients to recognize adverse drug reactions associated with antituberculosis medications.

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 : Romanian

20.

Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial.

Author: MisraU K, KalitaJ, NairP P

Aspirin effective
Aspirin reduces mortality
Aspirin well tolerated
Stroke risk

The study found that aspirin resulted in insignificantly lesser strokes and significantly reduced 3-month mortality in patients with tuberculous meningitis (TBM).

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

21.

Prevalence of Pyrazinamide Resistance in Khyber Pakhtunkhwa, Pakistan.

Author: KhanMuhammad Tahir, MalikShaukat Iqbal, AliSajid, Sheed KhanAnwar, NadeemTariq, ZebMuhammad Tariq, MasoodNayyer, AfzalMuhammad Tanvir

TB treatment
PZA resistance

Pyrazinamide (PZA) is crucial in TB treatment. This study aimed to assess the prevalence of PZA resistance in Pakistan, especially in the Khyber Pakhtunkhwa province, and its relationship with resistance to other TB drugs.

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

Language : English

22.

Safety and efficacy of additional levofloxacin in tuberculous meningitis: A randomized controlled pilot study.

Author: KalitaJ, BhoiS K, BetaiS, MisraU K

Tuberculous meningitis treatment
Seizures

This randomized controlled trial compared the safety and efficacy of adding levofloxacin to a standard four-drug antitubercular regimen (RHZE) in patients with tuberculous meningitis (TBM). There was no significant survival benefit in the RHZEL group compared to the RHZE group. However, the RHZEL group had a higher frequency of seizures.

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.

Language : English

23.

The association between cytochrome P450 polymorphisms and anti-tuberculosis drug-induced liver injury: a systematic review and meta-analysis.

Author: LiuXingren, RenSong, ZhangJingwei, XuDalin, JiangFeifei, JiangPeidu, FengJing, DengFei

TB treatment
ATDILI

This study systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to anti-tuberculosis drug-induced liver injury.

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

24.

[Tenosynovitis confirmed by MRI during anti-tuberculous treatment suspected due to isoniazid--2 case reports and literature review].

Author: YamamotoKei, TakasakiJin, MorinoEriko, KobayashiNobuyuki, SugiyamaHaruto

Tenosynovitis

Two cases of isoniazid-induced tenosynovitis, a rare side effect of anti-tuberculosis treatment, are presented. The condition was associated with isoniazid use in one case and improved after discontinuation. This highlights the importance of considering this side effect and using imaging techniques like MRI to aid diagnosis.

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 : Japanese

26.

Adverse effects of multidrug-resistant tuberculosis treatment with a standardized regimen: a report from Iran.

Author: BaghaeiParvaneh, TabarsiPayam, DorrizDonna, MarjaniMajid, ShamaeiMasoud, PooramiriMajid Valiollah, MansouriDavood, FarniaParisa, MasjediMohammadreza, VelayatiAliakbar

Auditory toxicity
Death
Hepatitis
Neurologic side effects
Rash
Renal toxicity

Treatment for multidrug-resistant tuberculosis (MDR-TB) can have adverse effects, including neurologic side effects (7.5%) and auditory toxicity (14.5%). Neurologic side effects were associated with a higher risk of death (odds ratio 13.8).

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

Language : English

27.

Niosomal encapsulation of the antitubercular drug, pyrazinamide.

Author: El-RidyMohammed Shafik, AbdelbaryAhmed, NasrEssam Amin, KhalilRawia Mohammed, MostafaDina Mahmoud, El-BatalAhmed Ibrahim, Abd El-AlimSameh Hosam

Improved drug delivery

Niosomes, a type of vesicle, were developed to deliver pyrazinamide (PZA) to treat tuberculosis. The most effective formulation was negatively charged niosomes with a Span 60:CH molar ratio of 4:2:1. This formulation showed promise in reducing the drug's side effects and enhancing its efficacy in guinea pigs.

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

Language : English

28.

Clinical evaluation and monitoring of adverse effects for fixed multidose combination against single drug therapy in pulmonary tuberculosis patients.

Author: Zaka-Ur-RehmanZeba, JamshaidMohammad, ChaudhryAkram

Tuberculosis treatment
Adverse effects

Fixed-dose combinations (FDCs) of TB drugs were found to be as effective as single drug formulations but with fewer side effects, making them a safer option for TB treatment.

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

29.

Cyclic Peptide [R<sub>4</sub>W<sub>4</sub>] in Improving the Ability of First-Line Antibiotics to Inhibit <i>Mycobacterium tuberculosis</i> Inside <i>in vitro</i> Human Granulomas.

Author: HernandezJoshua, AshleyDavid, CaoRuoqiong, AbrahemRachel, NguyenTimothy, ToKimberly, YegiazaryanAram, Akinwale DavidAjayi, Kumar TiwariRakesh, VenketaramanVishwanath

Enhanced drug delivery
Reduced antibiotic regimen

Cyclic peptide [R4W4] showed promise in controlling Mycobacterium tuberculosis (Mtb) infection in vitro human granulomas, particularly when combined with first-line antibiotics like isoniazid or pyrazinamide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
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

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