13.07.16 treatment regimens tb dr.delosreyes

8/13/2019 13.07.16 Treatment Regimens TB Dr.delosReyes

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TB Treatment Regimen

Gina S. de los Reyes, M.D.,MHPEd, FPCP, FPCCP


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Outline

Short Course Treatment; Fixed DoseCombination

Classification of TB CasesTreatment RegimensTreatment of TB in Special SituationsSymptom-based approach to adverse effectsof TB drugs


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When to suspect PTBCough of 2 weeks or more+/- night sweats, weight loss, anorexia,unexplained fever & chills, chest pain,fatigue & body malaise


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Terminology of TB ATS Classification

0- No TB Exposure1- TB Exposure, no

evidence of infection2 - TB infection, noevidence of disease3 - TB clinically active

4 - TB not clinicallyactive5 - TB suspect(diagnosis pending)

WHO Case Defn .Latent TB

Active TB Case

Pulmonary orExtrapulmonarySmear (+) or (-)


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Who requires treatment for PTB?1. Active PTB (Class 3)

2. Inactive PTB (Class 4) but with no previousadequate/completed treatment

3. TB suspect (Class 5) when the probability of

TB is high, while awaiting confirmation


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Aims of Treatment

1. To cure patients with the leastinterference with their lives

2. To prevent death in seriously ill patients3. To prevent extensive damage to the lungs

with the consequent complications4. To avoid relapse of the disease5. To prevent the devt of drug -resistant TB

(acquired resistance)6. To protect his/her family & the

community from infection


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Characteristics of Mycobacteria

Grow more slowly than otherbacteriaCan be dormantLipid-rich cell wall is impermeable tomany agentsIntracellular pathogensNotorious for their ability to developresistance


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Drugs used in mycobacteriatuberculosis

Combination of two or more drugs -to prevent emergence of resistanceduring the course of therapy

Treatment must be prolonged


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Anti-TB drugs : Actions & Adverse Effects

First line drugs

Gastronal Cutaneous rxnHepatitis

BactericidalRifampicin

HepatitisPeripheralNeuropathy

BactericidalIsoniazid

AdverseEffects

ACTIONDRUG


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Anti-TB drugs

OtotoxicityCutaneousHypersen-sitivity

BactericidalStreptomycin

Hepatotoxicity Arthralgia

BactericidalPyrazinamide

Retrobulbarneuritis

BacteriostaticEthambutol

DRUG ACTION Adverse Effects


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Second-line drugs

EthionamideProthionamideSodium para-aminosalicylate (PAS)CycloserineOfloxacin

Ciprofloxacin

CapreomycinKanamycinViomycin

AmikacinCo-amoxiclavClarithromycinRifamycin derivatives-Rifabutin,Rifapentene


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Drug Doses

DRUG DAILY (mkd)Isoniazid (H) 5 (4-6)Rifampicin (R) 8 (8-12)Pyrazinamide (Z) 25 (25-30)

Ethambutol (E) 15 (15-20)Streptomycin (S) 15 (12-18)
http://i88.photobucket.com/albums/k171/Circleline/Pills.jpg


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FIXED- DOSE COMBINATION(FDC) ANTI-TB DRUGS

Formulation where two or more anti-TB drugsare present in fixed proportions

Advocated by WHO & the International Union Against Tuberculosis & Lung Diseases(IUATLD) to replace single-drug preparations

as treatment for TB


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FDCs

For the patient: simplified drugintake

Fewer pills to swallow Pills are identical

Correct regimen is followed
http://img.alibaba.com/photo/100459182/Myrin_Tablet.summ.jpghttp://img.alibaba.com/photo/100459182/Myrin_Tablet.summ.jpg


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FIXED DOSE COMBINATION:SIMPLER DOSE COMPUTATION

Body Weight (kg) 4-FDC (HRZE)(75/150/400/275)

37 to 54 3 tablets

55 to 70 4 tablets

> 70 5 tablets

Practical dosing:

< 55 kg: 3 tablets daily> 55 kg: 4 tablets daily


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FIXED DOSE COMBINATION:SIMPLER DOSE COMPUTATION

Body Weight (kg) 2-FDC (HR)

50 (150/300)2 tablets

Other preparationsHRZHRE


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Short Course Chemotherapy6 months regimen which includesRifampicin and Pyrazinamide

Standard Treatment- at least 12 months(w/o Rifampicin)


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2 Phases of Short CourseChemotherapy

Intensive phase- 2 months

Continuation phase- 4 months

ex. 2HRZE4HR
http://notaids.com/images/tb.gif


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Objectives of SCC

To achieve better bactericidal

and sterilizing activities

To prevent emergence of

resistance
http://notaids.com/images/tb.gif


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Short Course ChemotherapyAdvantages

Easy to take Pt feels better quickly

Sputum becomes (-) quickly Relapse rate lower If relapse occurs, TB remains sensitive

Much cheaper than standard tx
http://whyfiles.org/221odd_air_hazards/images/tb_lungs.jpg


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Resistant Mutants

Small number which are naturally resistant

More will occur in TB cavityIf only one drug is given the sensitive TB aredestroyed but the resistant ones multiply

NEVER GIVE A SINGLE DRUG(MONOTHERAPY )
http://whyfiles.org/221odd_air_hazards/images/tb_lungs.jpg


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Classification of TB CasesPulmonary TB

Smear (+)Smear (-)

Extrapulmonary TB
http://images.google.com.ph/imgres?imgurl=http://www.wheelessonline.com/image6/cstb1.jpg&imgrefurl=http://www.wheelessonline.com/ortho/tuberculous_spondylitis&h=640&w=480&sz=16&hl=en&start=7&usg=__Qh3BSMbVnOSBvYu0MPT1tpwGEo4=&tbnid=GrVXnONuWUz2CM:&tbnh=137&tbnw=103&prev=/images?q=extrapulmonary+tuberculosis&gbv=2&hl=en&sa=Ghttp://whyfiles.org/221odd_air_hazards/images/tb_lungs.jpg


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Case Finding At least two (2) specimens from aquality assured laboratory

A case of pulmonary TB is alreadyconsidered as smear (+) if one out of 2specimens is positive for AFB.TB suspects with 2 negative smears onDSSM shall undergo other diagnostictests; e.g.CXR, TB culture


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Case findingSpecimens for culture and DST shouldbe obtained from ALL previously treatedpatients.

In settings were rapid molecular basedDST is available, the result should guidethe choice of the regimen
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PTB-Smear Positive

At least 1 sputum specimen (+) for AFB

+/- X-ray abnormalities consistentwith active TB
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PTB Smear Negative

At least 2 sputum specimens (-) for AFB

X-ray abnormalities consistent withactive TB

No response to a course of antibioticsand/or symptomatic medications

Decision by a medical officer to treatwith anti-TB drugs


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Extrapulmonary TB At least 1 mycobacterial smear/culture (+)from an extrapulmonary site

(organs other than the lungs: pleura, lymphnodes, gut, skin, joints, bones, meninges,intestines, peritoneum, pericardium, etc)

Histological and/ or clinical evidenceconsistent with active TB & there is decisionby a Medical Officer to treat pt with anti-TBdrugs


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Categories of TB Cases

New Previously Treated:

RelapseFailureReturn after default (RAD)

Transfer inOther


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Types of TB Cases New - pt who has never had tx for TB or whohas taken anti-TB drugs for < 1month

Relapse - pt. previously treated for TB, hasbeen declared cured or tx completed

Failure - pt while on tx is sputum smear ( + )at 5 months or later during the course of tx


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Types of TB Cases Return after default

A patient who returns to treatment withpositive bacteriology (smear or culture),following interruption of treatment for2 months or more

Transfer-in - pt who has been transferred

from another facility with proper referral slip tocontinue


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Types of TB Cases

Other1. Pt starting treatment again after interrupting

treatment for >2 mos. and has remained smear(-)

2. Pt who was initially registered as newsmear-negative case, turned out to be smear(+) during the tx.

3. Chronic case: pt who is sputum(+) at theend of a re-treatment regimen.


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Treatment RegimensRegimen TB Patient

Regimen I

2HRZE/4HR

New pulmonary smear (+)

casesNew seriously ill pulmonary

smear (-) cases with extensiveparenchymal involvement


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Regimen II:

2HRZES/1HRZE /5HRE

Failure cases

Relapse casesRAD (smear +)Other (smear +)


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Regimen III:2HRZE/4HR

Regimen IV:Refer tospecializedfacility or DOTSPlus

New smear (-) but withminimal PTB on x-ray as

confirmed by Medical Officer

Chronic case: Still smearpositive after supervisedre-treatment


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Treatment RegimensFor New Cases BOTH adult andchild:2HRZE/4HR


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Treatment Regimens Previously Treated Cases:

refer to Treatment Center /STC for furtherevaluation

Standardized Regimen with 2 nd line drugsIndividualized treatment regimendepending on drug sensitivity result

referred back for CAT II if pansusceptible2HRZES/ 1HRZE /5HRE


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Treatment RegimensFor extrapulmonary TB(brain,bones,joints):

Treatment is 9 12 months(2HRZE/7 10HR)


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Sputum follow-upNew (smear positive)

en d o f 2 n d

en d o f 5 t h

en d o f 6 t h

Previously Treated patientsen d o f 3 r d

en d o f 5 t h

en d o f 8 t h


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Treatment of TB in Special

Situations TB in pregnancy/lactation

TB in pts with hepatic disease TB in pts with renal disease TB in the elderly

TB in HIV/AIDS
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Tuberculosis in Pregnancy

INH, & Rifampicin, PZA &Ethambutol can be used

Take pyridoxine (Vit B6) 25 mg/daysince INH may cause demyelination Not recommended:

Streptomycin - Fetal ototoxicityFluroquinolones - arthropathies

Consensus Statement ( Phil. Practiceguidelines Group on Infectious Diseases)
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TB treatment in Pregnancy 2HRZE/4HR

Supplemental pyridoxine

Consensus Statement ( Phil. Practice guidelinesGroup on Infectious Diseases)
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TB and Lactation

Breast feeding not discouraged

Anti-TB drug concentration - low,non-toxic & non-therapeutic inbreast milk

Consensus Statement ( Phil. Practice guidelinesGroup on Infectious Diseases)
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TB treatment & Liver Disease

Hepatitis virus carriage or a past hx of

acute hepatitis w/o clinical evidence ofchronic liver disease

Rx- Usual short course chemotherapy

established chronic liver disease2SHRE/6HR or 2HRE/6HE2SHE/10 HE if extensive liver damage

Do liver function tests before initiating tx
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TB treatment & Liver Disease

Hepatic failure Streptomycin & Ethambutol can be given.

If a third drug is needed, Isoniazid orRifampicin can be given cautiously inlowered doses

Acute Hepatitis defer until hepatitisresolved or3SE/6HR

TB & l i ffi i /
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TB treatment & renal insufficiency/renal failure

Isoniazid, Rifampicin & Pyrazinamidecan be given in normal dosages

2HRZ/6HRStreptomycin & Ethambutol used withcaution (increase dosing intervals); Dosehalved if crea cl < 10mL/minDrugs given after HD to avoid drugfiltration
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Extrapulmonary TB For extrapulmonary TB(brain,bones,joints):

Treatment is 9 12 months

(2HRZE/710HR)

TB Meningitis Adjunctive therapy with Corticosteroids inTB meningitis & pericarditis
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Others TB in the Elderly

2HRZE/4HR

TB in HIV + 2HRZE/4-7HRInclude Rifampicin to hasten sputum

conversion

ARV should not be started at thesame time as anti TB meds to preventparadoxical reactions (immunereconstitution)
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Symptom-based approach toadverse effects of TB drugs

Reassure thepatient

Rifampicin3. Orange/redColored urine

Give anti-

histamine

Any kind of

drugs

2. Mild skin

reactions

Give meds atbedtime; orwith meals

Rifampicin1. Gastro-intestinalintolerance

ManagementDrugsresponsible

MinorSide-effects


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Pyridoxine (VitB6) 100-200mg for tx;10mg forprevention

Isoniazid5. Burningsensation ofthe feet

Warmcompress;Rotate sites ofinjection

Streptomycin4. Pain atinjection site

ManagementDrug(s)responsible

Side effects


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AntipyreticsRifampicin7. Flu-likesymptoms

(fever,inflammationof the resp.tract)

Aspirin orNSAID

Allopurinol

Pyrazinamide6. Arthralgia


Side effects


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Discontinue Anti-TB drugs

Any kind ofdrugs (espStrep)

1. Severe skinrash due tohypersensitivity

D/C anti-TBdrugs

If sx subside,resume tx &monitor

Any kind ofdrugs (esp

Isoniazid,Rifampicin &Pyrazinamide

2. Jaundicedue to hepatitis


Major sideeffects


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DiscontinueEthambutol &refer to anopthalmologist

Ethambutol3. Impairmentof visual acuity& color vision

(optic neuritis)DiscontinueStreptomycin

Streptomycin4. Hearingimpairment,

tinnitus,vertigo


Major sideeffects

Major side Drug(s) Management


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Major sideeffects

Drug(s)responsible

Management

5. Oliguria oralbuminuriadue to renaldisorder

StreptomycinEthambutol

DiscontinueStrep, Ethambutol

6. Psychosis& convulsion

Isoniazid DiscontinueIsoniazid

7.Thrombo-cytopenia,anemia,shock

Rifampicin DiscontinueRifampicin


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Drug interactionsRifampicin - potent inducer of thecytochrome P450 enzyme group;metabolism of oral contraceptives,

corticosteroids, oral anticoagulants &cyclosporin.Quinolones - inhibit some cytochrome

isoenzymes, leading to reducedmetabolism of certain drugs.


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Directly Observed Treatment (DOT)

All diagnosed TB patients should be offeredpatient-centered, DOT in health care facilitieswhenever possible, to monitor adherence &ensure completion of treatment

Self administered ( unsupervised) treatmentis not recommended


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Thank you for your attention!2HRZZZZZ

ZZZZZZ


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Case 1: 27/M, call center agent

Cough for 3 wks, productive of whitishphlegm, low-grade afternoon fever, weightloss (120 lbs decreased to 110 lbs), right-sided chest pain on coughing

3 yrs ago - History of treatment for PTB (Non-DOTS); unrecalled meds x 3 wks; lost tofollow-upSputum AFB negative for AFB 2xHbsAg (+); anti- HBs (+); LFTs normal,HIV (+)


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Case 2: 18/F pregnant24 weeks AOG, 52 kgproductive cough & sputum AFB smearpositive 1x

no chest xray was availableNo previous treatment for PTB


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Case 3: 62/M, vendorConsulted for non-massive hemoptysispreviously treated for TB (DOTS) 3 yrsago, declared cured

AFB (+) 1xWeight = 72 kg


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Case 4: 37/M construction worker

asymptomatic with incidental finding offibro-hazy infiltrates on chest X-ray forpre-employment clearance; AFB (+)

Treated for 2 mos. but stopped takingmedications 2 mos. agoHeavy alcohol drinker;

normal ALT, ASTWeight= 75 kg


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Case 5: 18/M asthmatic

Diagnosed with PTB 3, smear positiveHx of blurring of vision after 1 month oftreatment with HRZE, stopped medsWt= 45 kg


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Case 4: 52/F diabeticDiagnosed with PTB 3, smear positive,started tx 5 months agoOngoing treatment with INH and RifRepeat sputum smear (+)Weight = 56 kgCrea clearance = 9 ml/min

13.07.16 treatment regimens tb dr.delosreyes

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