TREATMENT OF TB/DR-TB IN

ETHIOPIA

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 Session objectives
• Discuss the individual anti-TB drugs used
in Ethiopia
• Discuss chemotherapy in TB treatment
• Describe the objective of TB treatment
• Treatment of Drug susceptible TB
• Treatment of Drug resistant TB
• Understand PMDT program design in
Ethiopia
Treatment of Tuberculosis
Objectives of treatment:
 To cure the patient
 To prevent death and late effects
 To prevent relapse of TB

 To prevent the development of acquired drug

resistance, and
 To decrease TB transmission.

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 Chemotherapy in TB
Drug Action
Adapted from: Caminero JA, et al. Treatment of TB. Eur Respir Monogr 2012; 58: 154–166.

Prevention of Bactericidal Sterilising Toxicity

Activity Resistance activity activity

High Rifampicin LowRifampicin Ethambutol

Isoniazid
Isoniazid Pyrazinamid Rifampicin
Rifampicin
Ethambutol New Fq Isoniazid
Fluoroquinol.
Injectables Injectables Fluoroquinol.
Fluoroquinol. Fluoroquinol. Injectables Injectables
Moderate Ethionamide Linezolid Linezolid Pyrazinamid Moderat
Cycloserin
PAS
Linezolid
Low High
Ethionamide
Pyrazinamid Isoniazid Rest
Pyrazinamid
 Treatment of Tuberculosis(2)
Anti-TB treatment is said to be adequate if
administered:
 In appropriate combination of drugs;
 In the correct dosage;
 Regularly taken by the patient, and
 For a sufficient period of time.

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 TB Treatment groups

Treatment
TB type Patient registration groups Remark
using

New TB patients with either  

bacteriologically or clinically FLD
New cases confirmed.
Four drugs
with RHZE

TB patients who had TB treatment FLD * previously treated TB patients

Previously history for at least one month in the are treated with the same
Four drugs
treated past, and now comes with regimen as New TB cases for six
bacteriologic or clinical diagnosis of with RHZE months after ruling out the
( re-treatment) TB. Or presence of resistance at least for
cases Rifampicin with rapid DST.
SLDs *
All TB patients with DST results  
RR-/M/XDR- showing resistant bacillary strain for Second line
TB cases at least rifampicin. drugs

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 Standardized TB Treatment
• One treatment regimen for a defined
patient group with similar characteristics.
• One standardized Frist line Anti-TB
treatment regimen to be administered
both for “New” and “previously treated
TB patient with evidence of susceptibility
to at least for Rifampicin

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 Standardized TB Treatment
Advantages over individualized prescription of drugs:
• Errors in prescription are reduced;
• Estimating drug needs, purchasing, distribution and
monitoring are facilitated;
• Staff training is facilitated;
• Costs are reduced;
• Maintaining a regular drug supply when patients move
from one area to another.
• Treatment Outcome evaluation.

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TREATMENT OF DRUG
SUSCEPTIBLE-TB

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 Phases of Treatment
The treatment of TB has two phases:
1. Intensive (Initial) phase:
• Duration 8wks
• All patients must swallow their drugs daily
• under direct observation of HWs (DOT)
• It renders the patient non- infectious (kills actively multiplying TB
bacilli)
Continuation phase:
• Follows the intensive phase - Consists of 2 drugs for 4- months

• All TB patients must take drug on daily bases/DOT

• Ensures that the patient is permanently cured and doesn’t relapse.

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Anti-TB Drug coding and treatment
regimens:

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 FLDs formulations available for treatment of DS-TB
DRUGS Formulation Strength (mg) Preparation Remark

HRZE tablet 75/150/400/275mg FDC

HR tablet 75/150mg FDC

E tablet 400mg Loose To be used in special

Adult

situations
management
STM Powder for inj. 1000mg Loose To be used in special
situations
management
H tablet 300mg Loose

RHZ dispersible tab 60/30/ 150 mg FDC * To be introduced in

(75/50/150)mg* Dec., 2017
Pediatric

RH dispersible tab 60/30mg FDC * To be introduced in

(75/50)mg* Dec., 2017

E tablet 100mg Loose

H tablet 100mg Loose

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Standard TB treatment regimen
Standard Regimen
Patient registration groups receiving
TB Patient type
Intensive the regimen
Continuation phase
phase
 New TB patients
 Relapse
 Treatment after LTFU
 Treatment after failure of New
2(RHZE) 4(RH) regimen
Drug  Others
susceptible TB
(New and
Previously  New patients with CNS
treated) TB( meningitis, tuberculoma)
 New TB patients involving vertebra
2(RHZE) 10 (RH) and Osteoarticular space

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 Dosing of TB treatment
The dose and the type of the drugs depend on:-

1. The age of the patient

2. The weight range of the patients

• NB: There is no sex specific difference in TB treatment

unless the patient is a pregnant mother.

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 Adult Dosing for susceptible TB cases
Patients weight Treatment regimen and Dose for New
(Kg)
Intensive phase: Continuation Phase:
2(RHZE) 4(RH)

20-29 1½ 1½

30-39 2 2

40-54 3 3

≥55 4 4

N.B. all patients taking INH should receive Pyridoxine (Vitamin B6) supplement
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 A. Pediatric FDC dosing for children using
RHZ 60/30/150mg
A. Pediatric FDC dosing for children using (RHZ 60/30/150)

Continuation phase
Intensive phase (2 months)
  (4 months)
Weight(kg)
RHZ (60/30/150)mg RH (60/30) mg
E 100mg tablet
tablet tablet
4 to 6 1 1 1
7 to 10 2 2 2
11 to 14 3 2 3
15 to 19 4 3 4
20 to 24 5 4 5
25+kg Adult dosages recommended
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 B. Pediatric FDC dosing for children using
RHZ 75/50/150mg

continuation
Intensive phase (2 months) phase (4
Weight
months)
bands
RHZ 75/50/150mg RH 75/50mg
E 100mg tablet
tablet tablet
4-7kg 1 1 1
8-11kg 2 2 2
12-15kg 3 3 3
16-24kg 4 4 4
25+kg Adult dosages recommended

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ISONAIZID PREVENTIVE
THERAPY (IPT)
 Eligibility for Isoniazid Preventive
Therapy (IPT)
• IPT is provided to treat latent TB infection.

• Treatment of latent TB infection benefits those

population groups known to have higher risk of
progression to Active TB disease if infected.

• In Ethiopia it is recommended for 2 eligible groups :

1. Under-five children who are exposed to TB in the past
one year, &
2. People living with HIV regardless of their age.
 Dosage

Dosage of IPT

 Adults: -INH 300mg/day – for 6 months

 Children -10 mg/kg/day – for 6 months

o For those under 5 yrs.:- if they have household contacts with TB patients
& active TB is ruled out (irrespective of HIV status)

 Vitamin B6 (25mg/day) be supplied with INH for prevention of

neuropathy:

 The protective effect of IPT declines with time and the durability
ranges up to five years
 IPT Dose in Children
Number of 100 mg tablets
Weight Ranges (kg) Dose given (mg)
of INH per dose

<5 ½ tablet 50

5.1-9.9 1 tablet 100

10-13.9 1 ½ tablet or ½ adult tablet 150

14 -19.9 2 tablets 200

20 -24.9 2 ½ tablets 250

>25 3 tablets or one adult tablet 300

 Contraindications of IPT:
 Active tuberculosis.

 Symptoms compatible with tuberculosis, even if the diagnosis of

TB cannot be confirmed.

 Abnormal chest X-ray.

 History of poor compliance with treatment.

 Active hepatitis (chronic or acute).

 Known or reported high daily alcohol consumption.

 Prior allergy or intolerance to isoniazid

 Follow up of patients on IPT
a) Patients on IPT need monthly follow up
 Monitor for signs and symptoms of drug toxicity:-

 Jaundice, anorexia, nausea, Vomiting or Abdominal pain, numbness, tingling,

skin rash, etc.

 Evaluate for signs and symptoms of active TB and assess for and counsel on
adherence

b) Isoniazid drug-drug interactions:

 Phenytoin, warfarin, and carbamazepine (their serum levels may increase).

 Ketoconazole and diazepam (their serum levels may decrease).

 Procainamide and chlorpromazine (the half-life of isoniazid can be increased)

c) INH and Drug-resistant TB:

 Providing IPT to people living with HIV does not increase the risk of developing
INH-resistant TB

 Regular TB screening for those taking IPT

TREATMENT OF DR-TB IN
ETHIOPIA

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SLD Groups

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 Cont…
• Put in order of usual preference
• Groups A, B and C are considered core SLDs
• Group D are add-on agents(added to the regimen if
effective medicines can not be composed)
• Lnz and Clf- are revised to be core SLDs
• Pas is currently considered as an add on
agent(previously used as a core SLD)
• Clarithromycin and other macrolides are no longer
included among the medicines to be used for the
treatment of MDR-TB
 Principles of regimen Design
• Regimen with at least five effective TB medicines during the
intensive phase is recommended, including pyrazinamide
and four core second-line TB medicines - one chosen from
group A, one from group B, and at least two from group C

• If the minimum of effective TB medicines cannot be

composed as above, an agent from group D2 and other
agents from D3 may be added to bring the total to five

• It is recommended that the regimen be further strengthened

with high-dose isoniazid and/or ethambutol (if they are
considered to add benefit)
 Cont…
• Never add a single new drug to a failing
regimen
• Avoid drugs with strong contraindication of
use (i.e. drug-drug interactions, cross resistance,
overlapping toxicities, history of severe allergy)
• Duration of the intensive phase of at least 8
months or and a total treatment duration of at
least 20 months is recommended in patients
without any previous MDR-TB treatment.

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 Approaches to regimen designing
Strategies
Standardized:
All patients in a defined group receive the same regimen based on drug resistance survey
data from representative populations. Used in Ethiopia.

Individualized:
Regimen based on patient’s treatment history and individual DST.

Empiric:
Regimen based on the patient’s previous history of anti-tuberculosis treatment and DRS data
from representative populations. Common in children.

Standardized followed by individualization:

Patient will be put on standardized regimen and could later be modified upon obtaining
additional pattern on DST. Preferred in Ethiopia.

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Recommended Regimens in
Ethiopia
 Standardized Regimen(85%elligable)

1. Short treatment regimen (70%)-9 to 12 month

4-6 Km Mfx Pto Cfz Z High dose INH E/ 5 Mfx Cfz Z E
• Exclusion criteria
– Confirmed resistance, or suspected ineffectiveness, to a
medicine in the shorter MDR-TB regimen (excluding
resistance to isoniazid)
– Previous exposure for >1 month to a second-line medicine
included in the shorter MDR-TB regimen
– Intolerance to one or more medicines in the shorter MDR-
TB regimen or increased risk of toxicity (e.g. drug-drug
interactions, cardiotoxicity)
– Pregnancy
– Extrapulmonary disease

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 Cont…
2. Standardized conventional regimen (15%)
• 8 Z Cm Lfx Pto Cs / 12 Z Lfx Pto Cs
• Benefiting groups: patients with
– Extrapulmonary disease
– Pregnancy
– Intolerance to a medicine in the regimen (eg Z, INH,
E)
*if no drug is compromised in this group

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 Individualized regimen (15%)
• New anti-TB drugs containing
individualized regimen (8%)
– e.g. 6 Cfz,Dlm,Z,Mfx,PAS/14 Cfz,Z,Mfx,PAS

• Not containing new anti-TB drugs (7%)

– e.g 6 km,Pas,Z,lnz,INH/2 Pas,Z,Lnz,INH/12
PAs,Z,Lnz,INH

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 Cont…
• Benefiting groups:
– Patient treated for more than one month with short regimen,
interrupts treatment and returns after an interval >2 months

– Lack of response to treatment (e.gs. no sputum smear conversion

by 6 months or deterioration of clinical condition despite treatment

– DST results showing resistance to medicines in the shorter MDR-

TB regimen: this may reflect the actual situation at start of
treatment which was unknown at that time, or else the acquisition
of additional resistance during treatment etc…

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 DR-TB Treatment
Monitoring and Follow Up
• Every patient needs to be evaluated regularly
to ensure clinical improvement and adhering
well.
• Patient monitoring while treatment includes:
– Improvement in clinical conditions
– Improvement in smear and culture results
– Screening for possible encounter of Adverse
events
– Adherence to treatment and practice of DOT

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PMDT Program Design in
Ethiopia
 Program design

• Clinic-based Ambulatory Model of care: is

designed to deliver the treatment course
on outpatient basis so long as the patient is
fit to be followed as outpatient.
• In the delivery of DR-TB treatment to
patients in Ethiopia, health facilities could
serve as either treatment initiating centers
(TIC) or treatment follow up centers
(TFC).
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 Treatment initiating centers (TIC):

• Health facilities selected to provide comprehensive patient care and

treatment services for DR-TB patient

• The clinical panel of team in these centers is authorized:

– To initiate treatment with SLDs
– To perform all scheduled clinical evaluation and lab monitoring tests,
– To manage difficult cases and those with serious complications and/or ADR
and
– To decide on the need of regimen modification when indicated.

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 Treatment follow up centers (TFC):

- Are health facilities providing TB-DOTS services where

clinically stable patients are referred to continue to treatment.
- Aims to decentralize the delivery of treatment services closer to
the patient residence.
- Involve in case finding process of DR-TB
- Routine screening of adverse events, supervise DOT and
administer injection

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 DR-TB Management Teams

• PMDT is supported by different technical

and managerial teams at different level of
the health system:

– Technical working group at national and

regional level (mainly for programmatic
support )
– Panel team at every TIC

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 Cont…
Panel team:
Refers the team composed of clinical and managerial
staffs at every TIC.
Aims to:
• Assist smooth implementation of the program, &
• Provide clinical and psychosocial care to patient at
service delivery points.
The team is expected to meet every month to review
patients’ profiles and decide on major actions and
document the clinical decisions
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 Cont…

• Team composition:
Clinicians from MDR-TB center, nurses,
pharmacist, laboratory technologist, chief
Clinical officer, social workers, local health
office (-regional, zonal &/or woreda) TBL
officers, and technical advisors from
partner.

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 Cont…
Responsibilities of the team include:
 To decide on the appropriate regimen for an individual patient

 Evaluation of clinical and social profile of each patient who is about start treatment

 Decision on mode of treatment initiation for individual patient

 To construct individual treatment regimen when needed

 Arrangement of social support for eligible patientsTo decide patient’s transfer to

respective TFC

 Ensure the implementation of minimum TB IC package at TIC and TFC

 To assist TFCs, together with the program, to practice standard of care.

 to practice monthly inventory of SLDs and other related commodities

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Role of pharmacy personnel in Treatment and Adherence support

• Ensure regular availability of SLDs

• Member of MDRTB panel team and involve in
drug selection, monitoring and managing of
ADRs
• Ensure appropriate dispensing and dosage,
prevent medication error
• Support patient treatment adherence with the
panel team
• Involve in clinical mentoring to TFCs and
program support activities with panel team
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