Slide 1

R.VINOEDH NAIDU @ PRP U41HSB (2014/2015)PRECEPTOR : PUAN NADIATUBERCULOSISTUBERCULOSIS & Its management&Its management

LEARNING OBJECTIVESTo learn about the definition & diagnosis of TB

To learn about the investigations & algorithm of investigations of TB

To learn about the treatment target groups & treatment regimens of TB

To understand different treatment aspects involved in tuberculosis treatment management

2INTRODUCTIONTuberculosis , a multisystemic disease with numerous presentations and manifestations, is the most common cause of infectious diseaserelated mortality.

Mycobacterium tubeculosis @ Tubercle Bacilli (TB)

Number of TB cases in the country continues to increase. *

High rates of morbidity & mortality due to:Delayed presentationAdvanced HIV

3

3EPIDEMIOLOGYTop 3 causes of death for women aged 15 to 44 yearsOne quarter of all deaths in people living with HIV TB death rate dropped 41% between 1990 & 2011

44TEN LEADING CAUSES OF DEATH (WHO Factsheet, 2008)5WorldDeaths in millions% of deathsIschaemic heart disease7.2512.8%Stroke & other cerebrovascular disease6.1510.8%Lower respiratory infections3.466.1%Chronic obstructive pulmonary disease3.285.8%Diarrhoeal diseases2.464.3%HIV/AIDS1.783.1%Trachea, bronchus, lung cancers1.392.4%Tuberculosis1.342.4%Diabetes mellitus1.262.2%Road traffic accidents1.212.1%TB is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent.

5ESTIMATED TB INCIDENCE RATE, 2011 6

6TB TransmissionDots in air represent droplet nuclei containingM. tuberculosis

TB Pathogenesis

Symptoms associated with TBCoughCough up bloodChest painsFeverNight sweatsWeak and tiredWeight lossLoss of appetite

DIAGNOSIS11Detection of acid fast bacilli (AFB) on smears & culture of M. tuberculosis from clinical specimens.

SPUTUMAcid fast bacilliCULTURE & SENSITIVITY

1112

12CHEST X-RAYIMAGING may assist in: identifying the lesioncharacterising the lesionassessing the extent/severity assisting in intervention

Findings may mimic other diseases.

It is important to know that Imaging is NOT for diagnosis of TB. It may ONLY suggest the possibility of the disease especially pending lab diagnosis.

13EDUCATIONNature of disease Adherence with prolonged treatment Risks of defaulting treatment Side effects of medication Risks of transmission & need for respiratory hygiene*

1414NEW CASES PTB156-month regimen consisting of :

INTENSENSIFICATION2 months of EHRZ (2EHRZ)

MAINTENANCE4 months of HR (4HR)

2 EHRZ + 4 HR2 EHRZ + 4 H3R32 E3H3R3Z3 + 4 H3R315RECOMMENDED ANTI-TB DRUGSDRUG

RECOMMENDED DOSESDaily3X a weekDose (range) in mg/kg body weightMax in mgDose (range) in mg/kg body weightMax in mgIsoniazid (H)5 (4 - 6)30010 (8 - 12)900Rifampicin (R)10 (8 - 12)60010 (8 - 12)600Pyrazinamide (Z)25 (20 - 30)200035 (30 40)*3000*Ethambutol (E)15 (15 - 20)160030 (25 35)*2400*Streptomycin (S)15 (12 - 18)100015 (12 18)*1500*16Pyridoxine 10 - 50 mg daily needs to be added if Isoniazid is prescribed*WHO. Treatment of Tuberculosis Guidelines (4th Ed.), 20116IMPORTANT POINTSRifampicin *should be used for the whole duration of treatment.*Rifampicin dosage should not be lower than recommended dosage (10 - 12 mg/kg).

Pyrazinamide beyond 2 months during the intensive phase does not confer further advantage if the organism is fully susceptible.

17

17MAINTENANCE PHASEIn new patients with PTB, WHO recommends daily dosing throughout the course of antiTB treatment.

However, a daily intensive phase followed by thrice weekly maintenance phase is an option provided that each dose is directly observed & patient has improved clinically.

.18

1819FIXED-DOSE COMBINATION (FDC) IN MALAYSIAForecox-Trac Film Coated Tab: isoniazid, rifampicin, ethambutol & pyrazinamide Rimactazid 300 Sugar Coated Tab: isoniazid, & rifampicin Rimcure 3-FDC Film Coated Tab: isoniazid, rifampicin & pyrazinamideAkurit-Z Tab: isoniazid, rifampin (rifampicin) & pyrazinamideAkurit Tab: isoniazid & rifampin (rifampicin) Akurit-Z Kid Dispersible Tab: isoniazid, rifampin (rifampicin) & pyrazinamideAkurit-4: ethambutol, isoniazid, rifampin (rifampicin) & pyrazinamide

19FDC IN MOH4-Drug combination: isoniazid 75 mg, rifampicin 150 mg, pyrazinamide 400 mg & ethambutol 275 mg tab

3-Drug combination: isoniazid 75 mg, rifampicin 150 mg & pyrazinamide 400 mg tablet

30 - 37 kg body weight: 2 tablets daily 38 - 54 kg body weight: 3 tablets daily 55 - 70 kg body weight: 4 tablets daily More than 70 kg body weight: 5 tablets daily

COMPLIANCE & LESS PRESCRIPTIONS ERRORS

2020FIRST LINE TREATMENTDRUGMECHANISMSIDE EFFECTSISONIAZIDInhibits bacteria cell divisionJoints pain, vitamin B6 deficiencyPYRAZINAMIDEKills bacteriaUric acid retention, goutRIFAMPICINKills bacteria, metabolized via bile and body fluidsRed-colored urine, nausea, vomiting, rashes, fever, jaundice in alcoholicETHAMBUTOLSynergistic with RifampicinReduced visionSTREPTOMYCINInhibits bacterial activityOtotoxic, nephrotoxic, DIRECTLY OBSERVED THERAPY (DOT)Direct observation of drug ingestion of the DOTS component should not be the sole emphasis in TB control programmes. Enhanced DOTS can reduce incidence of TB within a community (p=0.04)Cavalcante SC et al., Int J Tuberc & Lung Dis. 2010

22

22

DOT during office hour only by trained personnelNo take awayCan DOT at any KK or KD

LIVER IMPAIRMENT24Baseline LFT prior to treatment

Regular monitoring at weekly & biweekly intervals during the initial 2 months

If LFTs are more than 3X upper limit of normal before initiation of therapy, a regimen containing fewer hepatotoxic drugs can be considered

The likelihood of drug induced hepatitis is greater & is potentially life threatening

Fluoroquinolones & aminoglycosides can be utilised to make up a less hepatotoxic antiTB regimen

24ANTITB DRUGS IN LIVER IMPAIRMENT25DrugsDurationIsoniazid & rifampicin, plus ethambutol9 monthsEthambutol given until isoniazid susceptibility is documentedIsoniazid, rifampicin, streptomycin & ethambutol, followed by isoniazid & rifampicin2 months

6 monthsRifampicin, pyrazinamide & ethambuthol6 - 9 monthsIsoniazid, ethambutol & streptomycin,followed byisoniazid & ethambutol2 months

10 months Streptomycin, ethambutol & fluoroquinolones18 - 24 monthsProgressively more severe liver disease25RENAL IMPAIRMENT2 months of isoniazid, rifampicin, pyrazinamide & ethambutol followed by 4 months of isoniazid & rifampicin

Significant renal excretion of ethambutol & metabolites of pyrazinamide occurs, hence doses must be adjusted to intermittent dosing

Pyrazinamide should be administered after hemodialysis to avoid premature drug removal

All 4 antiTB drugs can be administered after hemodialysis to facilitate DOT

Avoid streptomycin

2626ANTITB DRUGS IN RENAL IMPAIRMENT27DrugChange in frequency?Recommended dose & frequency IsoniazidNo changeMax 300 mg PO once dailyRifampicinNo changeMax 600 mg PO once dailyPyrazinamideYes25 - 30 mg/kg per dose PO 3 times per weekEthambutolYes15 - 25 mg/kg per dose PO 3 times per week27

ADVERSE DRUG REACTION (ADR)A response to a medicine which is unintended or harm which occurs at a normal dosage during normal use. 28ONSET OF ADR FOR ANTITBADRs occur within early stage of the treatment compared to the later stage.Defnition of ADR: Side effect of drug might also imply that the effect can be beneficial but ADR refer to the harm associated with the use of given medications at a normal dosage during normal use.ADR onset: 52.5% experience ADRs within 20 days, 7.5% in 21 - 40 days, 22.5% within 41 - 60 days and 17.5% in >60 days after starting treatment.2829Treat symptomatically WITHOUT treatment interruptionCLASSIFICATION OF ADR FOR ANTITB29Age >40 years Overweight/obesity Smoking Alcoholism Anaemia Baseline ALT more than twice upper limit of normalBaseline aspartate aminotransferase more than twice upper limit of normal EPTB MDR-TB medication HIV infection CD4 count