isoniazid
Regulatory sources consulted
Approved indications
- Susceptible active tuberculosis always in combination and preventive treatment of tuberculosis infection under an approved regimen.
Contraindications
Absolute
- Acute liver disease; prior isoniazid-associated liver injury; prior severe adverse reaction or hypersensitivity to isoniazid.
Clinical warnings
- It may cause severe or fatal hepatitis even months after initiation. Assess age, alcohol, and liver-disease risk; monitor symptoms and liver tests and discontinue according to label thresholds. — DailyMed, set_id 93252cc8-c8d4-401b-bde5-ca8a3b57651e
- Major warning · It may cause peripheral neuropathy, seizures, and a lupus-like syndrome; give pyridoxine to people at neuropathy risk. — DailyMed, set_id 93252cc8-c8d4-401b-bde5-ca8a3b57651e
- It may cause severe skin reactions, including SJS, TEN, DRESS, and AGEP; discontinue immediately if suspected. Cerebellar syndrome has been reported, especially in chronic kidney disease. — DailyMed, set_id 93252cc8-c8d4-401b-bde5-ca8a3b57651e
Drug interactions
- HighAlcohol
Mechanism: It increases hepatotoxicity risk.
Recommendation: Avoid alcohol and monitor liver function.
DailyMed, set_id 93252cc8-c8d4-401b-bde5-ca8a3b57651e
- HighPhenytoin or carbamazepine
Mechanism: Isoniazid may increase their concentrations and toxicity.
Recommendation: Monitor concentrations and neurologic symptoms and adjust.
DailyMed, set_id 93252cc8-c8d4-401b-bde5-ca8a3b57651e
- ModerateHistamine- or tyramine-rich foods
Mechanism: They may cause headache, palpitations, or flushing.
Recommendation: Avoid excess and seek advice if symptoms occur.
DailyMed, set_id 93252cc8-c8d4-401b-bde5-ca8a3b57651e
Adverse events
Common (≥1%)
Increased transaminases, peripheral neuropathy, nausea, and rash
Rare but serious
Fulminant hepatitis, seizures, agranulocytosis, cerebellar syndrome, and severe skin reactions
Pregnancy and lactation
Use for active tuberculosis during pregnancy when benefit justifies risk. Breastfeeding should not be discouraged because of isoniazid, but milk concentrations are insufficient to prevent or treat tuberculosis in the infant.
Recent literature (PubMed)
Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to rifampicin and isoniazid, or rifampicin alone) is a burgeoning public health challenge in several parts of the world, and especially Eastern Europe, Russia, Asia and sub-Saharan Africa. Pre-extensively drug-resistant TB (pre-XDR-TB) refers to MDR/RR-TB that is also resistant to a fluoroquinolone, and extensively drug-resistant TB (XDR-TB) isolates are additionally resistant to other key drugs such as bedaquiline and/or linezolid. Collectively, these subgroups are referred to as drug-resistant TB (DR-TB). All forms of DR-TB can be as transmissible as rifampicin-susceptible TB; however, it is more difficult to diagnose, is associated with higher mortality and morbidity, and higher rates of post-TB lung damage. The various forms of DR-TB often consume >50% of national TB budgets despite comprising <5-10% of the total TB case-load. The past decade has seen a dramatic change in the DR-TB treatment landscape with the introduction of new diagnostics and therapeutic agents. However, there is limited guidance on understanding and managing various aspects of this complex entity, including the pathogenesis, transmission, diagnosis, management and prevention of MDR-TB and XDR-TB, especially at the primary care physician level.
One of predominant contributors to global mortality is tuberculosis (TB), an infection caused by Mycobacterium tuberculosis (MTB). Inappropriate and ineffectual treatment can lead to the development of drug-resistant TB. One of the most common forms of drug-resistant TB is multidrug-resistant tuberculosis (MDR-TB), caused by mutations in the rpoB and katG genes that lead to resistance to anti-TB drugs, rifampicin (RIF) and isoniazid (INH), respectively. Although culturing remains the gold standard, it is not rapid thereby delaying potential treatment and potentially increasing the incidence of MDR-TB. In contrast, molecular techniques provide a highly sensitive and specific alternative. This review discusses the classification of biomarkers used to detect MDR-TB, some of the commonly used anti-TB drugs, and DNA mutations in MTB that lead to anti-TB resistance. The objective of this review is to increase awareness of the need for rapid and precise detection of MDR-TB cases to decrease morbidity and mortality of this infectious disease worldwide.
Tuberculosis (TB) is a global health challenge and one of the leading causes of death worldwide. In the last decade, the TB treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid, and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, and SHINE) and drug-resistant TB (STREAM, NiX-TB, ZeNix, and TB-PRACTECAL). Dose optimization of rifamycins and repurposed drugs has also brought hopes of further development of safe and effective regimens. Consequently, international and WHO clinical guidelines have been updated multiple times in the last years to keep pace with these advances. This narrative review aims to summarize the state-of-the-art on treatment of drug-susceptible and drug-resistant TB, as well as recent trial results and an overview of ongoing clinical trials. A non-systematic literature review was conducted in PubMed and MEDLINE, focusing on the treatment of TB. Ongoing clinical trials were listed according to the authors' knowledge and completed consulting clinicaltrials.gov and other publicly available websites (www.resisttb.org/clinical-trials-progress-report, www.newtbdrugs.org/pipeline/trials). This review summarizes the recent, major changes in the landscape for drug-susceptible and drug-resistant treatment, with a specific focus on their potential impact on patient outcomes and programmatic TB management. Moreover, insights in host-directed therapies, and advances in pharmacokinetics and pharmacogenomics are discussed. A thorough outline of ongoing therapeutic clinical trials is presented, highlighting different approaches and goals in current TB clinical research. Future research should be directed to individualize regimens and protect these recent breakthroughs by preventing and identifying the selection of drug resistance and providing widespread, affordabl
Tuberculosis (TB) affects more than 10 million people each year. We have contested this burden with a paradoxically slow development of treatments, as compared to other infectious diseases. This review aims to update health care professionals on the last developments for the management of TB. The combination of drugs established more than 40years ago is still adequate to cure most people affected by TB. However, with the generalisation of regimens based on rifampicin and isoniazid for (only) 6months, resistance emerged. Resistant cases needed long treatments based on injectable drugs. Now, after an exciting decade of research, we can treat resistant TB with oral regimens based on bedaquiline, nitroimidazoles, and linezolid for (only) 6months, and we may soon break the 6-month barrier for treatment duration. However, these improvements are not enough to end TB without an engagement of people affected and their communities to achieve adherence to treatment, transmission control, and improve socioeconomic determinants of health.
Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets. The use of targeted NGS to diagnose drug-resistant tuberculosis, as described in publicly available data, has not been comprehensively reviewed. We aimed to identify targeted NGS assays that diagnose drug-resistant tuberculosis, determine how widely this technology has been used, and assess the diagnostic accuracy of these assays. In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Global Index Medicus, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for published and unpublished reports on targeted NGS for drug-resistant tuberculosis from Jan 1, 2005, to Oct 14, 2022, with updates to our search in Embase and Google Scholar until Feb 13, 2024. Studies eligible for the systematic review described targeted NGS approaches to predict drug resistance in Mycobacterium tuberculosis infections using primary samples, reference strain collections, or cultured isolates from individuals with presumed or confirmed tuberculosis. Our search had no limitations on study type or language, although only reports in English, German, and French were screened for eligibility. For the meta-analysis, we included test accuracy studies that used any reference standard, and we assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes for the meta-analysis were sensitivity and specificity of targeted NGS to diagnose drug-resistant tuberculosis compared to phenotypic and genotypic drug susceptibility testing. We used a Bayesian bivariate model to generate summary receiver operating characteristic plots and diagnostic accuracy measures, overall and stratified by drug and sample type. This study is registered with PROSPERO, CRD42022368707. We identified and scre