Module 5: Principles of Treatment

Session Overview

– Aims of TB Treatment – General Principles– Treatment Guidelines

Learning Objectives

• Describe 3 basic principles of TB treatment

• Explain the difference between the 4 treatment categories (Cat I-IV)

• Understand and describe when and why a regimen may be extended

Aims of TB Treatment

• Cure the patient of TB

• Prevent death from active TB or its latent effects

• Prevent relapse of TB

• Decrease transmission of TB to others

• Prevent the development of acquired resistance

Fundamental Responsibility and Approach in TB Treatment

• Assure that appropriate regimen is prescribed by MOs

• Ensure successful completion of therapy

(adherence)

• Utilize directly observed therapy (DOT) as standard-of-care

Adherence

•Nonadherence is a major problem in TB control

•Patient education is the most effective tool to prevent default—USE IT!!

•Use case management and directly observed therapy (DOT) to ensure patients complete

treatment

Why Do Patients Default?

• As their condition improves they may feel better and decide they don’t need meds

• They may experience side effects• Forgetfulness/lack of a reminder!• Travel to cattle posts without refills• Difficulty getting to clinic b/c of

work/distance

What is Case Management?

•Assignment of responsibility within clinic tooversee patient monitoring

-bacteriology-DOT-side effects

•Systematic regular review of patient data

•Plans in place to address barriers to adherence BEFORE default occurs

Directly Observed Therapy (DOT)

•Health care worker watches patient swallow each -Dose of medication

-Every pill, every day-Self-administered is NOT DOT

REMEMBER

DOT for all patients on all regimens

NO exceptions

DOT in Ghantsi…Can you identify the main elements?

Directly Observed Therapy (DOT)

•DOT can lead to reductions in relapse and acquired drug resistance

•Use DOT with other measures to promote adherence

•DOT is the key to CURE

Treatment of TB Disease

Factors Guiding Treatment Initiation

• Epidemiologic information– e.g., circulating strains, resistance patterns

• Clinical, pathological, chest x-ray findings

• Microscopic examination of acid-fast bacilli

(AFB) in sputum smears

Basic Principles of Treatment

•Determine the patient’s HIV status- this could save their life!

•Provide safest, most effective therapy in shortest time

•Multiple drugs to which the organisms are susceptible

•Never add single drug to failing regimen

•Ensure adherence to therapy (DOT)

Standard Treatment Regimen

• Initial phase: standard four drug regimens (INH, RIF, PZA, EMB), for 2 months

• Continuation phase: additional 4 months

Treatment of TB for HIV-Negative Persons

•2 months HRZE followed by 4HR

•Four drugs in initial regimen always- Isoniazid (INH)

- Rifampin (RIF)

- Pyrazinamide (PZA)

- Ethambutol (EMB) or streptomycin (SM)

(Streptomycin replaces Ethambutol in TB meningitis)

Treatment of TB for HIV-Positive Persons

•Management of HIV-related TB is complex and patient care needs to be coordinated withIDCC

•HIV-infected patients already on ARVs who develop TB should begin anti-TB meds immediately

•Patients on 1st line ARVs may start Category I ATT.•Patients on ARV regimen with efavirenzshould be reviewed by a specialist.•If patient is on 2nd or 3rd line ARVs discuss with specialist before starting ATT.

• HIV-infected TB patients should be evaluated for ARVs immediately– Pts with CD4<=200 should start ARVs

within two weeks after start of ATT– Pts with CD4s>200 may defer until end of

ATT

Treatment of TB for HIV-Positive Persons

Extrapulmonary TB

•In most cases, treat with same regimens used for pulmonary TB

Bone and Joint TB, Miliary TB, or TB Meningitis in Children

•Treatment extended > 6 months depending on site of disease

•In TB meningitis Streptomycin replaces Ethambutol

ChildrenChildren are at an increased risk for TB

disease• If the disease is severe (meningitis,

military TB, etc.) use Category I treatment, SM replaces EMB in small children

• For less severe disease: treat with category III regimen

In most cases, treat with same regimens used for adultsInfants

Treat as soon as diagnosis is suspected

Infants and Children

Dosing of CPT in Children

Age and weight of child

Recommended daily dose

Suspension 5ML syrup =200mg/40mg

Child Tablet 100mg/20mg

Single strength adult tablet 400mg/80mg

Double Strength adult tablet 800mg/160mg

6 weeks to 6 months (<5kg)

100mg sulfamethoxasole/20mg trimethoprim 2.5ml 1 tablet n/a n/a

6 months to 5 years (5-15Kg)

200mg sulfamethoxasole/40mg trimethoprim 5ml 2 tablets 1/2 tablet n/a

6 to post pubertal

400 mg sulfamethoxasole/80mg trimethoprim 10ml 4 tablets 1 tablet 1/2 tablet

Post pubertal and Adults

800 mg sulfamethoxasole/160mg trimethoprim n/a n/a 2 tablets 1 tablet

Multidrug-Resistant TB (MDR TB)

•Presents difficult treatment problems• Lengthy, multi-drug regimen• Side effects common• Management complex

•Treatment must be individualized

•Clinicians unfamiliar with treatment of MDR TB should seek expert consultation

•Always use DOT to ensure adherence

Multidrug-Resistant TB (MDR TB) Con’t

• 6 months intensive treatment (always including an injectable drug) followed by at least an 18 month continuation phase

• Only specialist physicians at the referral hospitals can initiate MDR treatment

Treatment Monitoring

• Sputum smear microscopy for AFB at 2 months and 6 months– If positive at two months, repeat at 3

• If still smear positive at 3 months, continuation phase (4HR) is still started while awaiting DST results

• Continue drug-susceptibility tests if smear-positive after 3 months of treatment

Caused by Adverse Reaction Signs and Symptoms

Any drug Allergy Skin rash

Ethambutol Eye damage Blurred or changed vision

Changed color vision

Isoniazid,

Pyrazinamideor

Rifampin

Hepatitis Abdominal pain

Abnormal liver function test

results

Fatigue

Lack of appetite

Nausea

Vomiting

Yellowish skin or eyes

Dark urine

Adverse Drug Reactions

Adverse Drug Reactions

Caused by Adverse Reaction Signs and Symptoms

Isoniazid Peripheral neuropathy

Tingling sensation in hands and feet

Pyrazinamide Gastrointestinalintolerance

Arthralgia

Arthritis

Upset stomach, vomiting, lack of appetite

Joint aches

Gout (rare)

Streptomycin Ear damage

Kidney damage

Balance problems

Hearing loss

Ringing in the ears

Abnormal kidney function test results

Caused by Adverse Reaction Signs and Symptoms

Rifamycins

• Rifabutin

• Rifapentine

• Rifampin

Thrombocytopenia

Gastrointestinal intolerance

Drug interactions

Easy bruising

Slow blood clotting

Upset stomach

Interferes with certain medications, such as birth control pills, birth control implants, and methadone treatment

Common Adverse Drug Reactions

Drug Interactions

• Relatively few drug interactions substantially change concentrations of antituberculosis drugs

• Antituberculosis drugs sometimes change concentrations of other drugs

-Rifamycins can decrease serum concentrations of many drugs, (e.g., most of the HIV-1 protease inhibitors), to subtherapeutic levels

-Isoniazid increases concentrations of some drugs (e.g., phenytoin) to toxic levels