1. FOLLOW-UP, REFERRAL & COMMON ADR OF ANTITB TREATMENT by Assoc. Prof. Dr. Tengku Saifudin Tengku Ismail Ms. Rahela Ambaras Khan 1

2. LEARNING OBJECTIVES To learn about follow-up schedule of newly diagnosed PTB patients To learn on type of cases required to be referred to specialists To learn of the common ADRs of antiTB drugs & their management 2

3. FOLLOW-UP All patients on antiTB treatment should be monitored to assess their response to treatment & to identify problems associated with it. All patients should be aware of symptoms indicative of PTB & adverse drug reactions. 3

4. NEW PATIENTS WITH PTB WHO recommends daily dosing throughout the course of antiTB treatment. A daily intensive phase followed by thrice weekly maintenance phase is an option. A maintenance phase with twice weekly dosing is not recommended since missing one dose means the patient receives only half the total dose for that week. 4

5. MALAYSIAN CPG TB 2002 Follow-up was recommended at 2, 4 & 6 months during treatment. Sputum smear & chest radiograph were recommended to be done during each follow-up clinic visit. 5

6. MALAYSIAN CPG TB 2012 Follow-up is recommended at 2, 4 & 6 months during treatment. In order to detect early adverse drug reactions & to enhance compliance, follow-up within 1 month of starting treatment is advisable. Sputum smear & chest radiograph should be done at 2 & 6 months if patient is clinically improving. 6

7. FLOW CHART FOR 6 MONTHS TREATMENT OF PTB 7

8. FOLLOW-UP Patients with initial sputum smear negative should have repeat sputum smear at 2 months of antiTB treatment. If still negative, no further sputum sample is required. If sputum smear remains positive at 2 months, refer to specialists with experience in TB management & repeat sputum AFB & sputum MTB C&S at 3 months. 8

9. FOLLOW-UP Patients with initial sputum positive should have repeat sputum smear at 2 & 6 months of antiTB treatment. Patients who remain sputum smear positive should be referred to specialists with experience in TB management. 9

10. FOLLOW-UP AFTER COMPLETION OF ANTITB TREATMENT Follow-up clinic visits should not be conducted routinely after treatment completion. Patients should be told to watch for symptoms of relapse & how to contact the TB service rapidly through primary care or a TB clinic. 10

11. DEFINITION OF ADVERSE DRUG REACTION (ADR) A response to a medicine which is unintended or harm which occurs at a normal dosage during normal use. ONSET OF ADR FOR ANTITB ADRs occur within early stage of the treatment compared to the later stage. Kishore PV et al., Pa J Pharm Sci, 2008 11

12. Nausea Tiredness Pruritus Minor rashes Troublesome but NOT SERIOUS Severe skin reaction (Steven- Johnson Syndrome, Toxic Epidermal Necrolysis & Drug Rash with Eosinophilia & Systemic Symptoms) Hepatitis Need IMMEDIATE DISCONTINUATION Treat symptomatically WITHOUT treatment interruption CLASSIFICATION OF ADR FOR ANTITB 12

13. Age >40 years Overweight/obesity Smoking Alcoholism Anaemia Baseline ALT more than twice upper limit of normal Baseline aspartate aminotransferase more than twice upper limit of normal EPTB MDR-TB medication HIV infection CD4 count <350 cells/mm 3 Hepatitis B virus infection Hepatitis C virus infection Concomitant use of other hepatotoxic drugs 1 Chung-Delgado K et al., PLoS ONE, 2011 2 Vilarica AS et al., Rev Port Pneumol, 2010 3 Khalili H et al., Factors DARU, 2009 4 Marzuki OA et al., Singapore Med J, 2008 RISK FACTORS OF ADR FOR ANTITB 13

14. SYSTEMS MOST AFFECTED BY ANTITB DRUGS Hepatobiliary Skin Gastrointestinal tract Skeletal system Renal 1 Shang P et al., PLoS ONE, 2011 2 Teleman MD et al., Int J Tuberc Lung Dis, 2002 14

15. Algorithm Severe Cutaneous ADRs Discontinue antiTB until the rashes subside Reintroduce individual drug sequentially to identify the offending drug Provide suitable regimen when an offending drug is identified (If possible, regimen should include 2 most potent drugs namely isoniazid & rifampicin ) Drug-Induced Pyrazinamide (MOST) Yee D et al., Am J Respir Crit Care Med, 2003 DRUG-INDUCED RASHES 15

16. Desensitisation?  If the offending drugs are both isoniazid & rifampicin  If a suitable drug combination is available, it is not necessary to perform desensitisation  It is done by careful administration of increasing doses of the drug under close supervision  Attempted in HIV patients*  Complex Cutaneous ADRs requires specialists consultation DRUG-INDUCED RASHES (cont.) 16

17. Risk Factors 1,2 Slow acetylators Old age Extensive TB disease Malnutrition Alcoholism Chronic viral hepatitis B & C infections Pregnancy until 90 days postpartum HIV Organ transplant recipients Drug-Induced Pyrazinamide (MOST) Isoniazid Rifampicin (LEAST) At least for the first 2 - 4 weeks is recommended among all patients with antiTB treatment as DIH usually occurs within the initial 2 months of treatment. Monitoring 1 Yew WW et al., Respirology, 2006 2 Blumberg HM et al., Am J Respir Crit Care Med, 2003 DRUG-INDUCED HEPATITIS 17

18. Restarting? Depends on whether hepatotoxicity sets in during the initial or the continuation phase of treatment & the amount of treatment received prior to the onset of such toxicity. DRUG-INDUCED HEPATITIS (cont.) 18

19. Serum transaminase level reaches 3 x ULN for patients with symptoms suggestive of hepatitis Serum transaminase level reaches 5 x ULN for those without symptoms When to Stop AntiTB? Restarting The patient can then be retreated with a regimen containing fewer potentially hepatotoxic drugs such as streptomycin, ethambutol, isoniazid & fluoroquinolones. DRUG-INDUCED HEPATITIS (cont.) 19

20. 20 DRUG-INDUCED HEPATITIS (cont.)

21. WHEN TO REFER The following conditions should be referred to specialists with experience in TB management: Unsure of TB diagnosis Retreatment of TB Adverse events following antiTB drugs MDR- & XDR-TB EPTB except TB lymphadenitis 21

22. WHEN TO REFER Renal &/or liver impairment with TB HIV-TB co-infection Smear negative TB Smear positive TB after 2 months of antiTB treatment All children diagnosed as TB Maternal TB Complex TB cases requiring surgical intervention 22

23. TAKE HOME MESSAGES All patients on antiTB treatment should be monitored to assess their response to treatment & to identify problems associated with it. All patients should be aware of symptoms indicative of PTB & adverse drug reactions. WHO recommends daily dosing throughout the course of antiTB treatment. Follow-up clinic visits should not be conducted routinely after treatment completion. 23

24. 24 THANK YOU  tengkusaifudin@yahoo.co.uk tengkusaifudin@yahoo.co.uk  rahelaambaraskhan@yahoo.com rahelaambaraskhan@yahoo.com