Table 2.

Assessment and monitoring for AE using active drug safety monitoring ^* .

	Targeted clinical assessment	Tests	Additional assessments only if second-line drugs are used
Before treatment	Presence of risk factors (see Table 1) Extent of TB disease/dissemination Pregnancy/breast feeding	Colour vision,† visual acuity Pregnancy (urinary/serum HCG) Mental health/neuropsychiatric assessment‡ HIV LFT (ALT), creatinine, CBC Hepatitis B/C serology HbA1c	If QT prolonging agents (FQs, CFZ, BDQ, DLM), measure electrolytes (K+, Ca++, Mg++) and ECG If DLM, measure albumin If ETH or PAS, measure TSH If aminoglycoside/CPM (now uncommon): assess hearing and bedside vestibular function. Formal pure tone audiometry for high frequency detection is optimal.
During treatment	Gastrointestinal upset Hepatotoxicity (e.g., anorexia, nausea, vomiting, fever, fatigue, pruritis, jaundice (icterus), abdominal discomfort, easy bruising/bleeding, hepatomegaly Joint pain/arthritis (gout) Neuropathy (e.g., tingling, numbness, burning hands or feet), altered gait, refusal to walk Blurry or altered vision (optic neuropathy) Rash; characterise nature and location/extent (e.g., mucosal involvement), severity, systemic features (fever, nausea) Pregnancy/breast feeding Neuropsychiatric disorders, including depression, anxiety, hallucinations, delusions – assess severity, presence of suicidal ideation Anaemia (tiredness, pallor shortness of breath)	Symptoms should prompt further clinical assessment and relevant testing (e.g., colour vision†/visual acuity, mental health assessment, LFT) Laboratory tests without symptoms or baseline abnormalities may not be needed unless risk factors are present (e.g., LFT in the presence of viral hepatitis or underlying cirrhosis) Consider tests for other causes, e.g., LFT derangement, test for hepatitis A (especially children)99 Rash, if severe, assess for organ dysfunction: LFT/creatinine, eosinophils (DRESS syndrome)	If QT prolonging agents (e.g., FQs, BDQ, CFZ, DLM), measure repeat electrolytes (serum K+, Ca++, Mg++) and ECG (QT interval) at 2w, 12w, 24w (or in case there are suggestive symptoms, e.g., dizziness, fainting, palpitations, syncope) If LZD, measure monthly CBC If ETH or PAS, monitor for hypothyroidism (every 2 months, additionally if clinically indicated) If FQs, assess for arthralgia, arthritis, tendonitis; be aware of rare AEs, such as raised intracranial pressure (headache) If CFZ, warn those undergoing treatment; monitor for skin discolouration, ichthyosis If aminoglycoside/CPM (now rare), assess regularly (monthly, 3/6 months after completion) for renal function and ototoxicity (hearing, vestibular dysfunction)

^* During treatment the frequency of review should be tailored to the individual person, treatment regimen/drugs used and the likely risk. Early during treatment and particularly during the intensive phase when most AEs are likely to occur review should be more frequent (e.g., every 2–4 weeks). During all phases additional review in case of new symptom development or concern is important.

^† For example, Ishihara testing to assess colour vision; charts are available online.¹⁰⁰

^‡ Mental health assessment tools that are accessible and assess the range of potential side effects across TB treatments are limited.¹⁰¹ Those that do exist may not be relevant and/or validated across populations (e.g., age, culture). Assessment should focus on AEs of the drug being used and use locally validated tools applicable to age.

AE = adverse effects; HCG = human chorionic gonadotropin; LFT = liver function test; ALT = alanine transaminase; CBC = complete blood count; HbA1c = glycated haemoglobin; FQ = fluoroquinolone; CFZ = clofazimine; BDQ = bedaquiline; DLM = delamanid; K⁺ = potassium; Ca⁺⁺ = calcium; Mg⁺⁺ = magnesium; ECG = electrocardiogram; ETH = ethionamide; PAS = para-aminosalicylic acid; TSH = thyroid stimulating hormone; LZD = linezolid; CPM = capreomycin; DRESS = drug reaction with eosinophilia and systemic symptoms; w = weeks.