Safe management of adverse events may warrant dose reduction or discontinuation of the component drugs. However, the BPaL regimen has been studied as a standardized course of treatment. Modification of the regimen through early discontinuation or replacement of any of the component drugs may result in poor treatment outcomes. Although dose modification of bedaquiline and pretomanid is not allowed, dose modification of linezolid is acceptable after the first month of treatment in cases of adverse events (see Section 6.5, which describes some acceptable modifications of duration in relation to missed doses).
The BPaL regimen may need to be discontinued in some patients. In such cases, patients need to be evaluated and treatment switched to an individualized longer regimen, based on the WHO guidelines for regimen design using priority grouping of medicines.
The most common situations in which the regimen may be discontinued are the following:
- Intolerable toxicity – One or more drugs may need to be suspended permanently owing to severe toxicity. In such cases, the clinician (or, preferably, clinical committee or consilium) should review the medical history and assess the patient carefully to determine what regimen should be prescribed.
- Treatment failure – If clinical and bacteriological responses to treatment are poor, a change in the treatment regimen should be considered. DST should be repeated, whether or not the regimen is changed, to inform future management decisions.
- Resistance to drugs in the BPaL regimen – For patients who submit a sputum sample for culturebased second-line DST at the beginning of treatment, results may not be available until after treatment has started. If resistance to BPaL component drugs is discovered after treatment is initiated, it will be necessary to discontinue the regimen.
- Pregnancy during treatment – For patients who become pregnant during treatment, it will be necessary to discontinue the BPaL regimen.
Regarding the discontinuation of any component of the BPaL regimen due to severe toxicity, the following factors should be taken into account:
- If either bedaquiline or pretomanid needs to be discontinued, the entire BPaL regimen should also be discontinued.
- If linezolid is permanently discontinued during the initial 4 consecutive weeks of treatment, the entire regimen should be discontinued.
- Temporary cessation of linezolid (due to a linezolid-specific toxicity) or of the full regimen is allowed for suspected drug-related toxicity. Re-introduction of the regimen could be considered after a cessation of no more than 35 consecutive days.
- If linezolid needs to be permanently discontinued at a later stage of the regimen, when the patient has already completed the initial 4 consecutive weeks of treatment with the linezolid 1200 mg daily dose, clinicians should assess patient status and consider discontinuing the regimen or continuing administration of bedaquiline and pretomanid for the rest of the regimen.
ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; BSL: blood sugar level; DST: drug susceptibility testing; ECG: ECG: electrocardiography; Hb: haemoglobin; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; TB: tuberculosis.
ᵃ Vital signs, TB symptom screen, pain, nausea, appetite and nutrition, diarrhoea, candidiasis. Clinical assessment should focus on a) monitoring response to treatment and b) addressing common symptoms associated with TB treatment and long-term antibiotic use, with the goal of supporting adherence.
ᵇ Food security, housing, mental state, substance use. Psychosocial assessment should offer an opportunity to assess supportive factors for treatment adherence and should be directly linked to relevant interventions wherever possible per country specific questionnaires.
ᶜ Xpert MTB/RIF, Hain GenoType MTBDRsl, culture-based second-line DST, next generation sequencing. If available, this should include Xpert/XDR and DST for the BPaL component drugs.