Avoiding peripheral neuropathy: Isoniazid induced peripheral neuropathy is preventable by the addition of pyridoxine 10 mg daily. This is given to patients at increased risk of neuropathy (diabetics, alcoholics, chronic renal failure or malnutrition, Asians).

Screening visual acuity: Ethambutol can be toxic to the eye. For this reason the BTS guidelines advise that visual acuity should be tested by Snellen chart before it is first prescribed. Ethambutol should only be used in patients who have reasonable visual acuity and who are able to appreciate and report visual symptoms or changes in vision. The notes should record that the patient has been told to stop the drug immediately if such symptoms occur, and to report to the physician. The general practitioner should also be informed of this. Rifampicin causes urine, tears, saliva and other body secretions to go an orange colour and can stain soft contact lenses.

Monitoring renal function: Renal function should be checked before ethambutol therapy (or aminoglycoside). Avoid these drugs if possible in renal failure and if they have to be used then serum levels should be monitored and the dosages adjusted.

Monitoring liver function tests: LFT's must be checked at the start of treatment. Both the patients and general practitioners should be clearly informed of drug side effects, the indications for stopping treatment and when to seek medical advice. Patients with chronic liver disease or are known to be alcoholic should have liver function tests carried out weekly for two weeks and then two weekly for the first two months. Many doctors continue to monitor liver function during treatment.

Response to abnormal LFT's: If a patient develops fever, malaise, vomiting, jaundice, or unexplained deterioration then treatment should be discontinued and liver function tests repeated. Other causes of liver disease should be considered. A modest elevation in ALT/AST after starting treatment is not uncommon. The BTS guidelines suggest that if the AST/ALT are two or more times normal, liver function should be monitored weekly for two weeks, then two weekly until normal. If the AST/ALT is under two times normal, liver function should be repeated at two weeks. If the AST/ALT level rises to five times normal or the bilirubin level rises, rifampicin, isoniazid and pyrazinamide should be stopped. Alternative treatment will need to be considered if the patient is unwell or is smear positive and within 2 weeks of starting treatment.

Re introducing TB therapy: After the LFT's have returned to normal, TB chemotherapy can be slowly reintroduced (isoniazid then rifampicin then pyrazinamide). Daily monitoring of LFT's and clinical status in hospital is paramount.

Step 1 Isoniazid 50 mg/day, increasing sequentially to 300 mg/day after 2-3 days if no reaction occurs monitor for 2-3 days

Step 2 Rifampicin 75 mg/day can be added, increasing to 300 mg after 2-3 days, and then to 450 mg (<50 kg) or 600 mg (>50 kg) after a further 2-3 days without reaction. monitor for 2-3 days

Step 3 Pyrazinamide 250 mg/day, increasing to 1. 0 g after 2-3 days and then to 1. 5 g (<50 kg) or 2 g (>50 kg).

Reference

Joint Tuberculosis Committee of the British Thoracic Society. Thorax 1998;53:536-548