Clinical Monitoring of People on Treatment
Education and counselling of eligible individuals Follow-up visits Adverse events Drug-drug interactions Treatment interruption and discontinuation Education and counselling of eligible individuals Education and counselling at treatment initiation should cover the following: what is TB exposure and infection? who is eligible for TPT? benefits of TB preventive treatment risks of TB preventive trea
Education and counselling of eligible individuals
Treatment interruption and discontinuation
Education and counselling of eligible individuals
Education and counselling at treatment initiation should cover the following:
- what is TB exposure and infection?
- who is eligible for TPT?
- benefits of TB preventive treatment
- risks of TB preventive treatment
- importance of adhering to treatment
- duration of treatment
- taking the medication - advice for the patients and caregivers:
- 3RH: Given on an empty stomach (before a meal)
- Isoniazid regimen only (6H or 12H): Give on an empty stomach (before a meal). Isoniazid is best absorbed on an empty stomach; there is an up to 50 per cent reduction in peak concentration with a fatty meal
- 3HP: Give with a meal or directly after a meal (Rifapentine is better absorbed with food)
- medicines they will be taking, frequency and timing
- possible side effects such as unexplained loss of appetite, nausea, vomiting, abdominal discomfort, persistent fatigue or weakness, dark-coloured urine, pale stools and jaundice
- infection control, including cough hygiene and adequate ventilation
- undesirable effects of using alcohol and smoking while on treatment
- what to do when experiencing adverse effects, which could include returning to a health facility
- develop an adherence plan together with the patient focusing on weekly or daily adherence strategies, depending on individual’s treatment regimen and support required during the treatment period (for an example of an adherence plan, see Annexure B).
Follow-up visits
Individuals should be monitored monthly (three or six months depending on the duration of treatment). For individuals with co-morbidities, try to align appointments with other scheduled chronic disease or ART visits to avoid multiple visits for care. At each visit the following must be done:
- screen individuals for signs and symptoms of TB. If symptomatic, investigate per National TB Management Guidelines, stop treatment. If asymptomatic, continue treatment
- provide on-going counselling and education of the individual
- monitor adherence (including pill count and missed appointments). If poor adherence or treatment interruption, ask about the possible reasons and counsel the individual. For children, counsel the parent/ guardian
- assess for need of social support and refer accordingly to social worker, community development officer, etc.
- assess individual for side effects of the medicines used for treatment, if any are present manage them
- people on the three-month treatment regimen can be given three months’ supply of treatment as part of multi-month dispensing (MMD). Those on longer treatment regimens (≥6 months) may be enrolled on central chronic medicine dispensing and distribution (CCMDD). Refer to the CCMDD Standard Operating Procedure (SOP) 12: Enrolment and management of patients on treatment for latent TB infection, treatment for DS-TB or drug resistant TB onto the CCMDD programme, for guidance.
Adverse events
While most of the adverse events are minor and occur rarely, specific attention should be paid to drug-induced hepato-toxicity, severe peripheral neuropathy as well as hypersensitivity. Assess individual for signs and symptoms suggestive of hepatitis such as new-onset vomiting, right upper quadrant pain and jaundice – if any of these are present, stop treatment immediately and refer to hospital for further assessment.
All adverse events should be reported using the standard reporting form as per the National Pharmacovigilance Centre (NPC) Guidelines (Annexure A).
Table 3. Management of common adverse events
| Adverse event | Drug(s) responsible | Signs/symptoms | Management |
| Peripheral Neuropathy | Isoniazid(H) | Tingling or burning sensation of the fingers and/or toes that usually occurs in a glove and stocking distribution | Vitamin B6 (pyridoxine) must be increased from 25mg to 100mg daily until the symptoms disappear. If the peripheral neuropathy is severe or worsens, then H should be discontinued immediately. Consider a Rifampicin only alternative TPT regimen. |
| Hepatotoxicity | Isoniazid(H) Rifapentine (P) Rifampicin (R) |
Symptoms: Nausea, vomiting, abdominal tenderness, discomfort near the ribs on the right upper abdomen, jaundice (yellowing of skin and whites of the eyes) Signs: Hepatic enlargement, increased liver function tests (LFTs) |
Stop Isoniazid and Rifampicin or Rifapentine immediately. Refer the individual to the hospital/ medical officer immediately for further evaluation. |
| Gastrointestinal Uncommon at recommended daily doses | Isoniazid(H) Rifampicin (R) Rifapentine (P) |
Symptoms: Nausea, vomiting, diarrhoea |
Rule out other causes. Conduct LFTs to rule out drug-induced hepatic dysfunction. Continue treatment based on severity of symptoms. Treat symptomatically (if no other cause is found). |
| Flushing reaction | Isoniazid(H) | Symptoms: Flushing and/or itching of the skin with or without a rash, hot flushes, palpitations, headache Signs: Increased blood pressure |
Reassure individual and inform about avoiding tyramine and histamine-containing foods (e.g. tuna, cheese, red wine) while receiving Isoniazid – consider a referral to a dietitian. Flushing is usually mild and resolves without treatment. If flushing is bothersome to the individual, an antihistamine may be administered to treat the reaction. |
| Mild itching rash | Isoniazid(H) Rifapentine (P) |
Mild rash and itching | Treat with antihistamine and topical steroid creams. |
| Hypersensitivity uncommon usually occurs –three to seven weeks after initiation of treatment | Isoniazid(H) | Symptoms: Hives (raised, itchy rash), fever (may occur) |
Discontinue treatment until the reaction resolves. |
| Hypersensitivity reaction occurs after the first three to four doses and begins approximately four hours after ingestion of medication | Rifapentine (P) | Symptoms: Flu-like symptoms, fever, headache, dizziness, shortness of breath, wheezing, nausea, muscle and bone pain, rash, itching, red eyes, hypotension or shock |
If mild reaction e.g. rash, dizziness, fever: Continue treatment and manage the adverse events. If severe reaction e.g. thrombocytopenia or hypotension, discontinue treatment and refer to hospital. |
Drug-drug Interactions
Points to note:
- Daily Rifampicin plus Isoniazid for three months (3RH) should not be given to infants and children on protease inhibitors (PI) or nevirapine-based ART due to drug-drug interactions.
- Rifapentine and INH (3HP) should not be offered to ART-naïve individuals starting Dolutegravir-containing ART due to lack of evidence at this stage. 3HP should be deferred until individuals have been on ART with a Dolutegravir-containing regimen until virally suppressed.
Table 4. Drug-drug interactions
| TPT drug | Drug-Drug interaction | Recommendation |
| Rifampicin decreases the levels of: | Dolutegravir | Double Dolutegravir dose to 50mg 12-hourly Offer Isoniazid monotherapy |
| Efavirenz | Offer Isoniazid monotherapy | |
| Protease inhibitors e.g. Lopinavir/Ritonavir | Offer Isoniazid monotherapy | |
| Rifapentine decreases the levels of: | Protease inhibitors e.g. Lopinavir/Ritonavir | Offer Isoniazid monotherapy |
| Nevirapine | Offer Isoniazid monotherapy | |
| Oral and implantable contraceptives | Use barrier method Offer injectable contraceptive method | |
| Dolutegravir | Offer Isoniazid monotherapy to ART naïve PLHIV |
Treatment adherence and completion of treatment
Adherence and completion of treatment are important for ensuring successful treatment and preventing the development of TB disease. Education and counselling must be provided on an ongoing basis.
Treatment interruption and discontinuation
Categorisation of treatment interruption
- Individuals who are initiated on the longer treatment regimens (six or more months) who interrupt treatment should be categorised as follows:
- interrupted treatment for less than three consecutive months
- interrupted treatment for more than three consecutive months
- interrupted treatment for a second time regardless of duration of interruption, despite adherence counselling
- Individuals who are initiated on the shorter regimens (three to four months) who interrupt treatment should be categorised as follows:
- interrupted treatment for less than four consecutive weeks
- interrupted treatment for more than four consecutive weeks
- interrupted treatment for a second time regardless of duration of interruption, despite adherence counselling
Individuals who interrupt treatment should be managed as outlined in Table 5.
Table 5. Management of individuals who interrupt treatment
| Duration of interruption | Management |
| If an individual misses one dose | For daily doses: The individual should take the missed dose as soon as they remember within the same day. If this is on the following day, take the next scheduled dose and continue with the regular schedule. Do not take two doses on the same day. For weekly doses: The individual should take the missed dose as soon as they remember within three days, continue the next dose as scheduled or start a new weekly schedule based on the day you took the missed dose. |
| If an individual interrupts treatment for less than one month for a short regimen or less than three consecutive months for a longer TPT regimen | - Enquire about the reasons for treatment interruption. - Address individual’s concerns. - Counsel the individual on the importance of adherence. - Screen clinically for TB symptoms. - If signs and symptoms of TB are present, conduct investigations to exclude TB. - If asymptomatic and no signs of TB disease, continue treatment including missed doses. |
| If an individual interrupts treatment for one or more month for a short regimen or three or more consecutive months for a longer TPT regimen |
- Enquire about the reasons for treatment interruption. |
| If an individual interrupts treatment for a second time regardless of duration of interruption, despite adherence counselling | Do not consider for retreatment. |
National Guidelines on the Treatment of Tuberculosis Infection, February 2023
Clinical Monitoring of People on Treatment