Safety Monitoring
Haematological Peripheral neuropathy Optic neuritis Haematological Anaemia in TB patients is common. It is often due to TB itself, a normocytic normochromic anaemia. Treating the TB treats the anaemia. There may be other contributing factors including nutritional deficiencies, blood loss from haemoptysis or other sources and HIV co-infection. TB patients are vulnerable to drops in Hb and may deco
Haematological
Anaemia in TB patients is common. It is often due to TB itself, a normocytic normochromic anaemia. Treating the TB treats the anaemia. There may be other contributing factors including nutritional deficiencies, blood loss from haemoptysis or other sources and HIV co-infection. TB patients are vulnerable to drops in Hb and may decompensate. The greatest safety concern is anaemia due to myelosuppression, caused by LZD. This can be life threatening. Most cases of anaemia occur in the first 2 months of therapy.
Prior to starting treatment: Ideally a full blood count with a differential white cell count and platelets needs to be done prior to starting treatment. However, from a practical point of view, healthcare providers can use a point-of-care test. If the Hb is above 8 g/dl, then BPaL-L can be started. If the Hb is below 8 g/dl, the treatment may need to be delayed until the anaemia is corrected patients with severe anaemia and RR TB should be admitted to hospital. If possible and acceptable, a transfusion of packed cells should be considered.
There is no evidence for using Bdq, Pa with Lfx or Mfx and introducing LZD later. As the patient’s bacillary load is high at this time, an inadequate regimen may result in amplification of resistance. If LZD may not be started, the PCAC or NCAC must be involved in the regimen design.
For the weeks 2 to 8: full blood count with a differential white cell count and platelets needs to be done every second week. However, from a practical point of view, a point of care Hb can be used. Again, if the Hb drops below 8g/l, the patient should be admitted for close follow up. If possible and acceptable, a transfusion of packed cells can be considered. A treatment interruption should occur if the patient is symptomatic.
For weeks 2, 4 and then weeks 8, 12, 16, 20 and 24: full blood count with a differential white cell count and platelets needs to be done every four weeks. However, from a practical point of view, a point of care Hb can be used. If the Hb drops below 8g/l, LZD can be stopped provided there has been a clinical response. This would include a reduction of symptoms, increase in weight, reduction in smear positivity, and if it has performed, culture conversion. LZD must be used for at least 2 months.
Peripheral neuropathy
This adverse event tends to occur later in treatment, with a peak time of onset around 16 weeks [23]. The patients’ experience of it is subjective.
Grade 3 peripheral neuropathy by the DAIDS tables is one that causes severe symptoms. This grade is applied if there is an inability to perform usual social and functional activities without intervention or if hospitalization is indicated. It is dependent on the individuals usual social and functional activities. This is too late. The key to detection and management of this condition is patient and healthcare provider education and counselling. As with most adverse events, pre-treatment counselling needs to include the common symptoms to watch out for: pins and needles, pain, and numbness. The BPNS is a useful and more objective guide to any worsening.
The severity of the TB, clinical response and mycobacterial response need to be considered. LZD remains a key drug in the regimen even in RR/MDR TB, withdrawal too early may compromise the efficacy of the regimen. Consult DR-TB experienced clinician/NCAC to assist if unsure if to continue or stop LZD.
Table 10.3.2.1 Management of peripheral neuropathy
| RR/MDR TB BPaL L | Pre-XDR TB B Pa L | |
| Weeks 1 to 8 | Consider reduction of dose or change to an individualized longer regimen without LZD | Change to an individualized longer regimen without LZD |
| Week 8 to 16 | Reduce the dose of LZD Consider permanent discontinuation if culture conversion has occurred |
Reduce the dose of LZD Consider permanent discontinuation if culture conversion has occurred |
| Weeks 16+ | Permanent discontinuation of LZD if culture conversion has occurred. Continue with Bedaquiline, Pretomanid and Levofloxacin. | Permanent discontinuation of LZD if culture conversion has occurred. Continue with BPa. |
Consider/manage contributing factors to peripheral neuropathy where possible (diabetes, chronic alcohol abuse). Treat pain adequately (use of pregabalin for example).
Optic neuritis
This is an uncommon adverse event but if left can cause permanent disability. Optic neuritis is usually bilateral.
It is important to establish a baseline for all patients about to start the regimen. An ophthalmological history should be taken. Prior visual problems including trauma, near-or shorted-sightedness, infections and cataracts should be recorded. Poor visual acuity prior to treatment is not a reason to withhold LZD. A full slit lamp examination is not necessary. Visual acuity should be measured using a Snellen test. It should be noted if the patients wear spectacles, and the Snellens should be done with them on. The tumbling E may also be used instead of Snellens chart. The visual acuity for each eye should be recorded as -/6 (20) R and -/6 (20) L. It is important that visual acuity be checked at every visit when the patient is on LZD. At each visit, the patient should be asked if there are any changes in visual acuity. If there is more than a two line drop in visual acuity, this requires action. If possible, the patient should be referred for (ophthalmology) assessment with a full examination of the optic nerve. If this cannot be done, then LZD should be permanently discontinued.
National Department of Health Clinical Management of Rifampicin-Resistant Tuberculosis, September 2023
Safety Monitoring