1. Unit 8: Complications and Special Situations Botswana National Tuberculosis Programme Manual Training for Medical Officers

2. Slide 8-2Unit 8: Complications and Special Situations Objectives At the end of this unit, participants will be able to: Manage Category I, II, and second-line therapy in special situations: Peripheral neuropathy Psychiatric illness and MDR Paradoxical reactions Pregnancy Breastfeeding Rash Liver disease Kidney Disease

3. Slide 8-3Unit 8: Complications and Special Situations Pregnancy Every woman of child bearing age should be asked if she is pregnant prior to starting anti-TB treatment Successful outcome of pregnancy largely depends on successful completion of anti-TB treatment Category I- drugs are safe in pregnancy Category II- Streptomycin should be avoided if possible as it can cause ototoxicity of the foetus

4. Slide 8-4Unit 8: Complications and Special Situations Pregnancy: Category IV If a woman is pregnant, if possible: Avoid the first trimester and start treatment during the 2nd or 3rd trimester Avoid amikacin (and streptomycin) until after delivery (fetal ototoxicity possible) Avoid ethionamide (teratogenic in animals)

5. Slide 8-5Unit 8: Complications and Special Situations Breastfeeding Women on Category I and II Regimens should continue breastfeeding If mother has smear+ TB and baby does not have active TB, give baby INH, as appropriate for weight, for 6 months followed by BCG vaccination Courtesy of: Jeanne Raisler

6. Slide 8-6Unit 8: Complications and Special Situations Rash in TB Treatment (1) Before attributing a skin symptom or rash to TB medications, assess Was it present before TB therapy began? Is it a condition unrelated to TB treatment? Many persons on TB treatment also have HIV Many people with HIV have skin conditions ARVs can also cause skin conditions, especially NVP

7. Slide 8-7Unit 8: Complications and Special Situations Rash in TB Treatment (2) Mild to Moderate rashes Skin rash with mild itching No blisters or mucous membrane involvement Management Consider other causes (scabies, etc.) Aqueous cream, Calamine skin lotion May need to stop TB medications Chlorpheniramine 4 mg tds, or Promethazine 25-50 mg nocte

8. Slide 8-8Unit 8: Complications and Special Situations Mild to Moderate Rash Source: I-TECH, 2006. Mild Rash

9. Slide 8-9Unit 8: Complications and Special Situations Severe Rash Rash with: Persistent itchiness Mucous membrane involvement and/or Blistering Urticaria (hives)

10. Slide 8-10Unit 8: Complications and Special Situations Severe Rash Source: I-TECH, 2006.

11. Slide 8-11Unit 8: Complications and Special Situations Severe Rash Management (1) Stop all TB drugs together Hospitalise the patient Give IV fluids as required Consider antibiotics for severe desquamation/exfoliation Treat like a burn Consider the use of steroids

12. Slide 8-12Unit 8: Complications and Special Situations Severe Rash Management (2) Most patients can wait for the rash to resolve before resuming TB treatment If the patient has life-threatening TB as well as life-threatening rash, may provide at least 2 TB drugs (3 drugs preferred) the patient has not taken before until the rash subsides

13. Slide 8-13Unit 8: Complications and Special Situations Treatment After Rash (1) If it is not obvious which caused the reaction, which is often the case, re-introduce TB medications in a step-wise fashion Gradually increase the dose of each medication If no reaction, continue the medication and gradually increase the dose of the next medication Use in reverse order of likelihood of cause of rash

14. Slide 8-14Unit 8: Complications and Special Situations Schedule for Reintroduction of Anti-TB Drugs DayDrug and dose 1INH 25 mg 2INH 50 mg 3INH 100 mg 4INH 200 mg 5INH 300 mg* 6INH 300 mg + R 150 mg 7INH 300 mg + R 300 mg 8INH 300 mg + R 450 mg 9INH 300 mg + R 600 mg* 10INH 300 mg + R 600 mg + E 400 mg 11INH 300 mg + R 600 mg + E 800 mg 12INH 300 mg + R 600 mg + E 1200 mg* 13INH 300 mg + R 600 mg + E 1200 mg + Z 500 mg 14INH 300 mg + R 600 mg + E 1200 mg + Z 1000 mg 15INH 300 mg + R 600 mg + E 1200 mg + Z 1500 mg 16INH 300 mg + R 600 mg + E 1200 mg + Z 2000 mg*

15. Slide 8-15Unit 8: Complications and Special Situations Treatment After Rash (2) If gradual reintroduction succeeds without a recurrence of rash, can continue treatment If the offending drug causes a reaction, suspend it and replace the offending drug with another agent May leave out pyrazinamide, ethambutol or streptomycin Get expert advice; substitutions may require longer duration of therapy

16. Slide 8-16Unit 8: Complications and Special Situations Liver Disease Three important issues complicate therapy: Hepatotoxicity of anti-TB drugs Acute liver disease with concurrent TB Chronic liver disease with concurrent TB Provided there is no clinical evidence of chronic liver disease, ATT is safe in patients with hepatitis virus carriage, history of acute hepatitis or excessive alcohol consumption

17. Slide 8-17Unit 8: Complications and Special Situations Acute Hepatitis Prior to TB Treatment Evaluate the cause: Viral (Hepatitis A, Hepatitis B) Alcohol ARVs Traditional medicines Other toxins If possible, await resolution of acute hepatitis before starting TB treatment

18. Slide 8-18Unit 8: Complications and Special Situations Acute Hepatitis Prior to TB Treatment (2) Consult TB expert Initial phase: SE for 3 months Continuation phase: RH for 6 months OR SE for 9 additional months Avoid Z, H, R and Eth (ethionamide) during acute hepatitis

19. Slide 8-19Unit 8: Complications and Special Situations Established Chronic Liver Disease Prior to TB Treatment Evaluate the cause Viral: Hepatitis B, Hepatitis C Alcohol Disseminated TB Avoid PZA Requires close monitoring Liver function tests Sputum samples Experienced TB doctor

20. Slide 8-20Unit 8: Complications and Special Situations TB Treatment with Chronic Liver Disease Preferred option Initial: 2 months RHES Continuation: 6 months RH Second option Initial: 2 months RES 10 months RE Third option Initial: 2 months HES Continuation: 10 months HE

21. Slide 8-21Unit 8: Complications and Special Situations Hepatotoxicity Symptoms: Fever, malaise, right upper quadrant abdominal pain, nausea, vomiting, loss of appetite Signs: ALT or AST more than 3x increased if symptoms of hepatitis are present, or more than 5x increased without symptoms Bilirubin or alkaline phosphatase more than 2x increased Jaundice

22. Slide 8-22Unit 8: Complications and Special Situations TB Drugs & Hepatotoxicity Hepatotoxic Pyrazinamide and isoniazid are the most common causes Pyrazinamide causes the most severe Rifampicin hepatotoxicity is less common and less severe Ethionamide NOT Hepatotoxic Ethambutol Streptomycin

23. Slide 8-23Unit 8: Complications and Special Situations Hepatotoxicity Try to rule out other causes of acute liver disease before attributing it to the TB treatment In hepatotoxicity, stop all TB drugs until the patient improves In case of severe TB, consider using “liver sparing regimen” (Ethambutol, streptomycin, and Ciprofloxacin) Admit patients to the hospital if unable to maintain hydration or if hepatic failure develops

24. Slide 8-24Unit 8: Complications and Special Situations Acute Hepatitis: During TB Treatment Rare Decision whether to stop or continue anti-TB treatment requires good clinical judgment Safest option in acute hepatitis not due to TB is to give streptomycin and ethambutol until the hepatitis has resolved (for a maximum of 3 months) followed by a continuation phase of INH and rifampicin for 6 months

25. Slide 8-25Unit 8: Complications and Special Situations Treatment After Hepatotoxicity (1) When hepatitis has resolved, reintroduce therapy If lab tests are not available, wait until 2 weeks after the jaundice ends If lab tests are available wait until AST/ALT < 2x normal Stepwise fashion, starting with safest drugs Try to create a safe combination regimen

26. Slide 8-26Unit 8: Complications and Special Situations Reintroduction of Drugs After Hepatoxicity Continue EMB, streptomycin, +/- ciprofloxacin INH 300 mg daily x 4 days If no symptoms, add Rifampicin 600 mg daily x 4 days If no symptoms, 2 options: Do not try PZA Try PZA D/C streptomycin and ciprofloxacin when back on E, H, R

27. Slide 8-27Unit 8: Complications and Special Situations Treatment After Hepatotoxicity (2) Pyrazinamide toxicity 2 months RHES then 6 months RH Check sputum at 2, 5, and 7 months Pyrazinamide and isoniazid toxicity 2 months RES then 10 months RE Check sputum at 2, 5, 8, and 11 months Pyrazinamide and rifampicin toxicity 2 months HES then 10 months HE Check sputum at 2, 5, 8, and 11 months

28. Slide 8-28Unit 8: Complications and Special Situations Renal Disease Some patients with active TB will have renal disease due to either TB in the urinary tract or another condition Adjust dose of ethambutol based on creatinine clearance if renal disease is suspected Avoid streptomycin unless specialist care is available Safest regimen: 2HRZ/4HR

29. Slide 8-29Unit 8: Complications and Special Situations Key Points Careful assessment is needed to distinguish drug reactions from other conditions Successful management of adverse drug reactions is necessary for patient health and integrity of the TB control program Treatment of patients with chronic liver or kidney disease may require changes in regimen or dosing Issues with category II regimen and second-line treatment are more complex