TB Treatment Regimen Gina S. de los Reyes, M.D., FPCP, FPCCP.

TB Treatment Regimen

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

Outline

Short Course Treatment; Fixed Dose Combination

Classification of TB Cases Treatment Regimens Treatment of TB in Special Situations Symptom-based approach to adverse effects

of TB drugs

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

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

3. TB suspect (Class 5) when the probability of TB is high, while awaiting confirmation

Aims of Treatment 1. To cure patients with the least interference with their lives. 2. To prevent death in seriously ill patients. 3. To prevent extensive damage to the lungs with the consequent complications.

4. To avoid relapse of the disease.

5. To prevent the dev’t of drug-resistant T.B (acquired resistance).

6. To protect his/her family and the

community from infection.

Anti-TB drugs : Actions & Adverse EffectsFirst line drugs

Gastro’nal

Cutaneous rxn

Hepatitis

BactericidalRifampicin

Hepatitis

Peripheral Neuropathy

BactericidalIsoniazid

Adverse Effects

ActionDrug

Anti-TB drugs

Ototoxicity

Cutaneous

Hypersen-

sitivity

BactericidalStreptomycin

Hepatotoxicity

Arthralgia

BactericidalPyrazinamide

Retrobulbar neuritis

BacteriostaticEthambutol

Second-line drugs

Ethionamide Prothionamide Sodium para-

aminosalicylate (PAS) Cycloserine Ofloxacin Ciprofloxacin

Capreomycin Kanamycin Viomycin Amikacin Co-amoxiclav Clarithromycin Rifamycin derivatives-

Rifabutin, Rifapentene

Drug Doses

Dosage in mg/kg (range)

Drug Daily Thrice/week

Isoniazid 5 10

(4-6) (8-12)

Rifampicin 8 10

(8-12) (8-12)

Drug Doses

Pyrazinamide 25 35

(28-30) (30-40)

Ethambutol 15 30

(15-20) (25-35)

Streptomycin 15 15

(12-18) (12-18)

FIXED- DOSE COMBINATION (FDC) ANTI-TB DRUGS

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

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

FDCs

For the patient: simplified drug intake

Fewer pills to swallow Pills are identical Correct regimen is followed

FIXED DOSE COMBINATION: SIMPLER DOSE COMPUTATION

Body Weight (kg) 4-FDC (HRZE)

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

Short Course Chemotherapy6 months regimen which includes

Rifampicin and Pyrazinamide

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

2 Phases of SCC

Intensive phase- 2 months

Continuation phase- 4 months

Short Course Chemotherapy Advantages

Easy to take Pt feels better quickly Sputum becomes (-) quickly Relapse rate lower If relapse occurs, TB remains sensitive Much cheaper than standard tx

Objectives of SCC

To achieve better bactericidal and sterilizing activities

To prevent emergence of resistance

Resistant Mutants

Small number which are naturally resistant More will occur in TB cavity If only one drug is given the sensitive TB are

destroyed but the resistant ones multiplyNEVER GIVE A SINGLE DRUG

(MONOTHERAPY)

Classification of TB Cases

Pulmonary TBSmear (+)Smear (-)

Extrapulmonary TB

PTB-Smear Positive

At least 2 sputum specimens (+) for AFB +/- X-ray abnormalities consistent with

active TB 1 sputum specimen (+) for AFB

and with X-ray abnormalities consistent with active TB

1 sputum specimen (+) for AFB with sputum culture (+) for M.

tuberculosis

PTB – Smear Negative

At least 3 sputum specimens (-) for AFB

X-ray abnormalities consistent with active TB

No response to a course of antibiotics and/or symptomatic medications

Decision by a medical officer to treat with anti-TB drugs

Extrapulmonary TB At least 1 mycobacterial smear/culture (+)

from an extrapulmonary site (organs other than the lungs: pleura, lymph nodes,

gut, skin, joints, bones, meninges, intestines, peritoneum, pericardium, etc)

Histological and/ or clinical evidence consistent with active TB & there is decision by a Medical Officer to treat pt with anti-TB drugs

Types of TB Cases New Relapse Failure Return after default (RAD) Transfer-in Other

Types of TB Cases New- pt who has never had tx for TB or who

has taken anti-TB drugs for < 1month

Relapse - pt. previously treated for TB, has been declared cured or tx completed, and is diagnosed with ( + ) smear or culture for TB

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

Types of TB Cases Return after default

A patient who returns to treatment with positive bacteriology (smear or culture), following interruption of treatment for 2 months or more.

Transfer-in- pt who has been transferred from another facility with proper referral slip to continue

Types of TB Cases Other 1. Pt starting treatment again after interrupting

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

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

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

Each standard drug is indicated by a capital letter.H- Isoniazid

R- Rifampicin Z- Pyrazinamide

E- Ethambutol S- Streptomycin

Treatment Regimens

Treatment RegimensRegimen TB Patient

Regimen I2HRZE/4HRE

New pulmonary smear (+ ) casesNew seriously ill pulmonary smear (-) cases with extensive parenchymal involvementNew severely ill extra-pulmonary TB cases


Regimen II:2HRZES/1HRZE/5HRE

Failure casesRelapse casesRAD (smear +)Other (smear +)


Regimen III:2HRZ/4HR

New smear (-) but with minimal PTB on x-ray as confirmed by Medical Officer New extra-pulmonary TB (not serious)

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

Tuberculosis in Pregnancy

INH, Ethambutol & Rifampicin can be used

Not recommended: Pyrazinamide, Streptomycin, Kanamycin, Capreomycin

Consensus Statement ( Phil. Practice guidelines Group on Infectious Diseases)

TB treatment in Pregnancy

Non-cavitary Disease -9HRE Cavitary Disease- 12HRE


TB and Lactation

Breast feeding not discouraged Anti-TB drug concentration - low,

non-toxic & non-therapeutic in breast milk


TB treatment & Liver Disease

Hepatitis virus carriage or a past hx of acute hepatitis w/o clinical evidence of chronic liver disease

Rx- Usual short course chemotherapyestablished chronic liver disease

2SHRE/6HR2SHE/10 HE

TB treatment & Liver Disease

Hepatic failure Streptomycin & Ethambutol can be given.If a third drug is needed, Isoniazid or

Rifampicin can be given cautiously in lowered doses

Acute Hepatitis – defer until hepatitis resolved or 3SE/6HR

TB treatment & renal insufficiency/

renal failure

Isoniazid, Rifampicin & Pyrazinamide can be given in normal dosages

2HRZ/6HR

Others TB in the Elderly

9HR

TB in HIV + with susceptibility testing

2HRZE/4-7HR

w/o susceptibility testingNon-cavitary- 9HRZECavitary -12HRZE

Symptom-based approach to adverse effects of TB drugs

Reassure the patient

Rifampicin3. Orange/red

Colored urine

Give anti-histamine

Any kind of drugs

2. Mild skin reactions

Give medication at bedtime

Rifampicin1. Gastro-intestinal intolerance

ManagementDrugs responsible

Side-effects

(Minor)

Pyridoxine (Vit B6) 100-200 mg for tx;

10mg for prevention

Isoniazid5. Burning sensation of the feet

Warm compress;

Rotate sites of injection

Streptomycin4. Pain at injection site

ManagementDrug(s) responsible

Side effects

AntipyreticsRifampicin7. Flu-like symptoms(fever, inflammation of the resp. tract)

Aspirin or NSAIDAllopurinol

Pyrazinamide6. Arthralgia


Side effects

Discontinue Anti-TB drugs

Any kind of drugs (esp Strep)

1. Severe skin rash due to hypersensitivity

D/C anti-TB drugs

If sx subside, resume tx and monitor

Any kind of drugs (esp Isoniazid, Rifampicin and Pyrazinamide

2. Jaundice due to hepatitis


Major side effects

Discontinue Ethambutol & refer to an opthalmologist

Ethambutol3. Impairment of visual acuity & color vision (optic neuritis)

Discontinue Streptomycin

Streptomycin4. Hearing impairment, tinnitus, vertigo


Major side effects

Major side effects

Drug(s) responsible

Management

5. Oliguria or albuminuria due to renal disorder

StreptomycinRifampicin

DiscontinueStrep, Rifampicin

6. Psychosis & convulsion

Isoniazid Discontinue Isoniazid

7.Thrombo-cytopenia, anemia, shock

Rifampicin Discontinue Rifampicin

Thank You for your kind attention!

2HRZE/4HR

2H3R3Z3E3/4H3R3

Challenge doses for detecting cutaneous or hypersensitivity to anti-TB drugs

Day 1 Day 2

Challenge Doses

Isoniazid 50mg 300mg

Rifampicin 75mg 300mg

Pyrazinamide 250mg 1.0g

Ethambutol 100mg 500mg

Streptomycin 125mg 500mg

Drug

TB Treatment Regimen Gina S. de los Reyes, M.D., FPCP, FPCCP.

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Transcript of TB Treatment Regimen Gina S. de los Reyes, M.D., FPCP, FPCCP.