Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It typically affects the lungs but can also affect other parts of the body. There are several drug regimens used to treat TB, with the primary first-line drugs being isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin. Treatment must continue for a sufficient time, such as 6-9 months, to fully cure the infection and prevent relapse or development of drug resistance. Second-line drugs are used for cases of drug-resistant TB or in cases where patients cannot tolerate first-line drugs. The goals of TB treatment are to cure the patient, prevent death, prevent relapse

1. Pharmacotherapy of
Tuberculosis
“We can not win the battle against HIV/AIDS if we do not
fight tuberculosis. TB is too often a death sentence for
people with AIDS. It does not have to be this way. We have
known how to cure TB for more than 50 years. What we
have lacked is the will and the resources to quickly
diagnose people with TB and get them the treatment they
need.”
Nelson Mandela, July 2004

2. Tuberculosis
• An infectious disease caused by M. TB complex and
usually affects the lungs, (extra-pulmonary 1/3rd of cases)
• Etiologic agents
1. M. tuberculosis ; the most common cause of human disease
2. M. bovis (transmitted by unpasteurized milk)
3. M. caprae (related to M. bovis)
4. M. africanum (isolated in West, Central, and East Africa)
5. M. microti (the "vole" bacillus, a less virulent and rare)
6. M. pinnipedii (a bacillus infecting sea lions in the Southern Hemisphere
and recently isolated from humans), and
7. M. canetti (a rare isolate from East African cases) 2

3. Tuberculosis
3
“TB is as Ancient as Humanity”
TB has co-existed with the Human Species
for more than 3 Million years

4. Tuberculosis
M. tuberculosis
• Rod-shaped
• Non-spore forming
• Thin aerobic (Oxygen and pH dependent)
• Very sensitive to heat, sunlight, and UV radiation
• Size(diameter) 0.5µm by 3µm.
• Cannot be decolorized by acid alcohol (AFB)
• Acid fastness is due mainly to the organisms' high content of
mycolic acids, long-chain cross-linked fatty acids, and other
cell-wall lipids. 4

5. Tuberculosis
5
U.V. Radiation therapy for
M. TB Sunlight therapy

6. Characteristics that contribute to survival
1. More than 60% of the cell wall is lipid, mainly mycolic
acids!
– Prevents many pharmacological compounds from getting to the
bacterial cell membrane or inside the cytosol.
2. An abundance of efflux pumps in the cell membrane.
– These transport proteins pump out potentially harmful
chemicals from the bacterial cytoplasm
– Responsible for the native resistance of mycobacteria to many
standard antibiotics
3. Tendency of some of the bacilli to hide inside the patient's
cells, thereby surrounding themselves with an extra
physicochemical barrier
6

7. Epidemiology
• Globally:
• Estimated 8.6 million cases(13% of them are HIV positive) in 2012
• And 5.7 million were new cases
• The majority of the cases were
• South-East Asia (29%), African (27%) ,Western Pacific (19%)
• India and China:26% and 12% of total cases, respectively.
• And 1.3 million deaths 2012
– About 75% of these cases were in African region???
• About 2.9 million new cases were women
» 410 000 died (160 000 are HIV-positive).
» Half of the HIV-positive people who died from TB in 2012 were women.
• Children:
– 530 000 TB cases (<15 years of age) and 74 000 TB deaths (among HIV-negative
children) in 2012 (6% and 8% of the global totals, respectively).
• MDR-TB
– 450 000 people developed and 170 000 deaths globally in
2012
7
2013 WHO report

8. Mode of transmission
• Commonly transmitted from a person with infectious
pulmonary TB by;
• Person-to-person
– Coughing or sneezing
– Speaking
• A single cough can produce 3,000 droplet nuclei and they can
remain suspended in the air for several hours.
8

9. Mode of …
9
Speaking
0-200 bacilli
Coughing
0-3,500 bacilli
Sneezing
4.500- 1, 000,000 bacilli

10. Factors influence the likelihood of
transmission
1. the number of organisms expelled into the air,
2. the concentration of organisms in the air
3. the volume of the space and its ventilation,
4. the length of time an exposed person breathes the
contaminated air, and
5. presumably the immune status of the exposed
individual

11. Techniques that are effective in
limiting airborne transmission of TB
1. Adequate room ventilation with fresh air
2. New construction or renovation of existing
facilities
3. Ultraviolet irradiation of air in the upper part of
the room
4. N95 disposable respirators for health care workers
and visitors during inside Tb patient ward/room

12. Infectivity of the TB case
• Highly infectious
– Smear positive pulmonary TB patients
• Less/non-infectious
– Smear–negative/culture-positive TB
– Culture-negative pulmonary and extrapulmonary TB
– TB with HIV co-infection
– TB in children
12

13. Risk factors
• Host factors
– Substance abuse
– Drug use
– Tobacco
– Alcohol
• Malnutrition
– Vitamin D; plays an important role in macrophage activation and
restriction of mycobacterial growth
– Iron status; Iron is an important growth factor for M. tuberculosis in
macrophages and appears to play an important role in host susceptibility
to TB infection. 13

14. Risk factors…
• Immune compromise
– HIV
– Glucocorticoids
– TNF inhibitors
– Transplant
• Social and environmental
factors
– Household contacts
– Birth in a TB-endemic
area
– Socioeconomic status
• The ability of the host to
respond to M. tuberculosis
may also be reduced by
certain diseases
– Malignancy
– Diabetes
– Renal disease
– Gastric surgery
– Celiac disease
– Minority groups
14

15. Clinical Presentation of TB
 The clinical presentation of TB varies depending on the
organ involved, age of the person and their immune
state.
 Clinical presentation in immunocompetent individuals is
most commonly the result of involvement of the lungs
(more than 80% of cases);
 however, organ specific presentations may be seen upon
involvement of extra-pulmonary organs, most commonly
lymph nodes, pleura, spine, joints, genito-urinary tract,
nervous system or abdomen:

16. Clinical Presentation of TB
 Persistent cough for two or more weeks, (cough of any
duration for HIV positives)
 Fever for more than 2 weeks
 Night sweats
 Unexplained weight loss(more than 1.5 kg in a month)
 Some patients may present with chest pains (due to pleurisy,
muscle strain), breathlessness, localized wheeze due to local
Tuberculosis bronchitis, or because of external pressure on the
bronchus by an enlarged lymph node
 chest X-ray abnormality

17. Extra-pulmonary TB:
 Patients may present with non-specific symptoms
such as unintentional weight loss, night sweats and
fever for more than 2 weeks.
 Other symptoms depend on the site or organ affected
 slowly developing painless swelling on the sides of the
neck is the commonest complaint of TB
lymphadenitis
 TB of CNS- focal neurological deficits, Seizures…

18. Diagnosis
Bacteriological Methods
A. Smear Microscopy-mainstay in resource limited settings
even if its limited sensitivity.
– Direct Sputum microscopy
B. TB Culture: a highly sensitive and specific; gold standard
C. Phenotypic DST diagnostic methods
D. Molecular Diagnostic methods
• Gene Xpert MTB/RIF Assay-rapid DNA test and is sensitive
– High risk for MDR TB, children, extra pulmonary TB and TB/HIV.
– preferred initial diagnostic test to increase yield 26

19. Additional supportive methods
A. Histo-Pathological Examination
– Fine needle aspiration
– Tissue biopsy-should be considered for the diagnosis of extra pulmonary TB
B. Radiological Examination; supportive
• It is sensitive but less specific.
• X-ray abnormalities suggestive of TB include;
– Upper lobe infiltrates (bi-lateral or uni-lateral),
– Cavitation
– Patchy, nodular shadows around the cavity.
C. Ultrasonography: is useful in the diagnosis of TB pleural
effusion, pericardial TB and peritoneal TB.

20. • A bacteriologically confirmed TB case is a patient from
whom at least one biological specimen is positive for
mycobacterium TB either by smear microscopy, Xpert
MTB/RIF, or culture.
• A clinically diagnosed TB case is a patient who does not
fulfill criteria for bacteriological confirmed case, but
diagnosed with active TB by an experienced clinician and is
decided to be given a full course of TB treatment.
28

21. Treatment of TB
• The goal of TB treatment:
– To cure the patient from TB
– To prevent death from TB disease and its late effects
– To prevent relapse of TB
– To prevent the development of acquired drug resistance,
and
– To decrease TB transmission
32

22. Treatment of TB
• To achieve the aims of TB treatment, the patient should
receive adequate chemotherapy
• Chemotherapy is considered to be adequate when it:
– Rapidly and substantially reduces the number of
actively multiplying bacteria.
– Cures patients
– Prevents relapse of the disease and
– Prevents the development of resistance to the drugs
33

23. Key Concepts in the Treatment of Tuberculosis
• Three basic concepts in TB treatment are :
(1) Regimens must contain multiple drugs to which the
organism is susceptible.
– to prevent the emergence of resistance.
(2) Drugs must be taken regularly.
– to prevent the emergence of resistance.
(3) Drug therapy must continue for a sufficient time.
– The organism has long latent time.
• Selection of drug must consider risk of adverse reactions.
34

24. Grouping of anti TB drugs
35

25. Drugs used for the chemotherapy of TB
First-line drugs:
• There are five currently recommended first-line agents
utilized as antituberculosis therapy.
• Are superior in efficacy and possess an acceptable degree of
toxicity.
• Include: Isoniazid (INH, H), Rifampin (R), Pyrazinamide (Z),
Ethambutol (E), and Streptomycin (S).
• Most patients with TB can be treated successfully with these
drugs.
36

26.  Some reports, however, include streptomycin among the
second-line drugs,
 since its use has declined in recent years, due to
 the high rates of resistance, and also,
 because other more effective drugs have been incorporated
 Similarly, new drugs such as the rifamycin derivatives
rifapentine and rifabutin can be considered among the
first-line drugs, and in the near future, it is quite likely that
some fluoroquinolones could be incorporated into the
standard antituberculosis treatment, thus being
considered as first-line drugs.

27. Drugs Used in Tuberculosis cont…
Second-line drugs
• Are either more toxic, less effective, or have not been
studied extensively.
• indicated only when the M. TB is resistant to the first-line
agents or in patients who cannot tolerate the first-line drugs.
• Therapy with second-line agents may be prolonged beyond
the standard period of treatment, depending on the clinical,
radiographic, and microbiological response to therapy.
– Include: Cycloserine, Ethionamide, Aminosalicylic acid, Rifabutin,
Fluoroquinolones, Capreomycin, viomycin, Amikacin, Kanamycin,
Clofazimine, Macrolides.
38

28. Second line anti TB drugs
39
Second-line agents
Amikacin 15 mg/kg/d
Aminosalicylic acid 8–12 g/d
Capreomycin 15 mg/kg/d
Ciprofloxacin 1500 mg/d, divided
Clofazimine 200 mg/d
Cycloserine 500–1000 mg/d, divided
Ethionamide 500–750 mg/d
Levofloxacin 500 mg/d
Rifabutin 300 mg/d
Rifapentine 600 mg once or twice weekly

29. Isoniazid (INH)
• INH is the most active drug for the treatment of tuberculosis
caused by susceptible strains.
• A synthetic agent with a structural similarity to that of
pyridoxine
• It is bactericidal for actively growing tubercle bacilli.
• INH is able to penetrate into phagocytic cells and thus is
active against both extracellular and intracellular organisms.
• INH inhibits synthesis of mycolic acids, which are essential
components of mycobacterial cell walls.
40

30. • Pharmacokinetics
• water soluble
• Well absorbed p.o. or i.m.
• Distributed widely: CSF  20% of plasma conc.
• but may reach close to 100% in the presence of
meningeal inflammation
• Metabolised by acetylation
 Fast acetylation t1/2  1hr
 Slow acetylation t1/2  3hr
43

31. 44
ANTIMYCOBACTERIAL…
• Therapeutic Uses
1) component of all TB chemotherapeutic regimens
2) alone is used to prevent
a) transmission to close contact at high risk of
disease
b) progression of infection in recently infected,
asymptomatic individuals
c) development of active TB in immunodeficient
individuals

32. 45
ANTIMYCOBACTERIAL…
• ADRs:
– Peripheral neuropathy (>5 mg/kg/day)– common in
pyridoxine (Vit B6) deficiency
– Hepatotoxicity
– Hypersensitivity reactions
• Other adverse effect
• Convulsion
• Optic neuritis
• Psychosis
• Drug interaction
 reduces metabolism of phenytoin (inhibits CYP2C9/10 )
 absorption is impaired by aluminum-containing antacids
reduced by adm. of 10 to 50 mg/day
vit. B6

33. Rifampin
• A large, semisynthetic lipid soluble molecule.
• Has a broader antimicrobial activity than INH.
Mechanism of action:
• binds to the -subunit of bacterial DNA dependent RNA
polymerase  inhibits RNA synthesis.
Pharmacokinetics
– well absorbed; distributed throughout the body
– excreted mainly through liver into bile
46

34. Antimicrobial spectrum: Rifampin
• is bactericidal for both intracellular and extracellular
mycobacteria, including
– M. tuberculosis, and atypical mycobacteria, such as M.
kansasii.
• Also active against Staphylococcus aureus, Neisseria
meningitidis, Haemophilus influenzae, Chlamydiae,
and certain viruses.
• is the most active antileprosy drug at present,
– but to delay the emergence of resistant strains, it is
usually given in combination with other drugs.
47

35. 48
ANTIMYCOBACTERIAL…
Therapeutic uses
a) Mycobacterial infection (pulmonary and
extrapulmonary TB)
 Bacteriocidal for intra & extracellular bacteria
b) Leprosy
c) Atypical mycobacteria
d) Prophylaxis and therapy of Meningitis & H.influenza
type b

36. 49
ANTIMYCOBACTERIAL…
Adverse effects
1) Hepatitis in pts with
 Preexisting liver disease
 High dose
 Alcoholics
 Elderly
 slow isoniazid acetylators on INH therapy
2) Hypersensitivity reactions
 Fever
 Interstitial nephritis
 Flushing
 Pruritis
 Thrombocytopenia

37. 50
ANTIMYCOBACTERIAL…
3. Imparts a harmless red-orange color:
– to urine, feces, saliva, sweat, tears, and contact
lenses.
– Patients should be advised of such discoloration of
body fluids.
Drug interaction
– is a strong microsomal enzyme inducer; enhances its own
metabolism as well as other drugs [warfarin, Steroids, HIV
protease inhibitors , NNRTIs, & ketoconazole]

38. Pyrazinamide
• Synthetic pyrazine analogue of nicotinamide
• Converted to pyrazinoic acid, active form of drug.
• MOA:
– inhibit the enzyme fatty acid synthetase 1 (FAS1), w/c
catalyzes the formation of long, saturated hydrocarbon
chains required for synthesis of mycolic acid
– inhibits mycolic acid biosynthesis.
• Bactericidal
• requires an acidic environment, such as that found in the
phagolysosomes, to express its tuberculocidal activity.
– highly effective on intracellular mycobacteria.
51

39. Pyrazinamide…
• Therapeutic use: TB
– No cross resistance with others
• Adverse effects
– GI intolerance
– Hepatotoxicity- major concern in 15% of
pyrazinamide recipients
– Hyperuricemia-inhibit excretion of urates
52

40. 53
ANTIMYCOBACTERIAL…
• ETHAMBUTOL
– Mechanism: Inhibits cell wall synthesis by blocking
arabinosyl transferase
– Therapeutic use: TB, as a fourth drug
– Majority of the unchanged drug is excreted in the
urine
– Adverse effects
• optic neuritis-occurs when your optic nerve is
inflamed
– C/I in children <6yrs
– Loss of visual acuity & red-green color blindness
• GI intolerance
• Hyperuricemia due to deceased uric acid excretion

41. Streptomycin
• An aminoglycoside antibiotic, (protein synthesis inhibitor)
• The first anti-TB drugs.
• Orally ineffective
• No penetration of living cells → cannot kill intracellular
bacilli
– Highly polar.
• Most M. tuberculosis strains, M. kansasii and M. avium-
intracellulare are sensitive.
• Indicated as a fourth drug in combination with isoniazid,
rifampin, and pyrazinamide in patients at high risk for drug
resistance.
• Also used in the treatment of streptomycin-susceptible
MDR tuberculosis. 54

42. Dosages of anti TB drugs
• The fixed dose combination (FDC):
– RHZE 150/75/400/275 mg
– RHZ 150/75/400 mg
– RH 150/75 mg
– EH 400/150mg
• These are TB drugs available as loose form:
– Ethambutol 400 mg
– Isoniazid 300 mg
– Streptomycin sulphate vials 1 gm
• All the drugs should be taken together as a single, daily
dose, preferably on an empty stomach 55

43. Phases of Chemotherapy
Intensive (initial) phase
• This phase consists of treatment with combination of four
drugs 2RHZE for new cases and 2RHZES/1RHZE for re-
treatment cases.
• It renders the patient non-infectious by rapidly reducing
the load of bacilli in the sputum, usually within 2-3 weeks
except in case of drug resistance.
56

44. Phases of chemotherapy
Continuation phase
• To ensure cure or completion of treatment.
• To prevent relapse after completion of treatment.
• This phase requires treatment with a combination of
– Two drugs, to be taken for 4 months for new cases and
– Three drugs for re-treatment cases for 5months.
57

45. TB treatment regimens
 New TB cases
• Other Previously treated Smear Negative PTB and EPTB cases who
were previously cured or treatment completed
• Regimen= 2RHZE/ 4RH
 Previously Treated TB Cases
– Defaulted patients coming with smear negative TB, EPTB, or
previously treated patients with unknown treatment outcome
– Regimen= 2S(RHZE)/1(RHZE)/5(RH)E
58

46. How to select the correct TB treatment regimens
2S(RHZE)/1(RHZE)/5(RH)E

47. How to select the correct TB treatment regimens…

48. Anti-TB drug dosages
• The dose and type of anti-TB drugs are age & weight
dependent.
• Pregnant should not be given streptomycin.
61
WHO-TB guideline 2014

49. Anti-TB Drug Doses
62
Anti-TB drugs dosage for previously treated cases
Anti-TB drugs dosage for new TB cases

51. Extra pulmonary TB
• In order of frequency, the extrapulmonary sites most
commonly involved in TB are the;
– Lymph nodes
– Pleura
– Genitourinary tract
– Bones and joints
– Meninges
– Peritoneum
– Pericardium.
• Symptoms of extra-pulmonary TB:
• Symptom complex of TB, plus features related to the pathology of the affected
organ.
64

52. 99

53. TB and HIV co-infection
• HIV infection and active TB disease should be started on ART
irrespective of CD4 cell count
• However,TB treatment should have to be given a priority
It is recommended that ART be initiated as soon as TB
therapy is tolerated.
Ideally, this may be as early as 2 weeks and not later than 8
weeks.
100

54. Initiation of ART in TB patients already on anti-TB
• In TB patients infected with HIV, treatment with anti-retroviral
drugs (ARV) may interact with treatment of TB.
– Reduced efficacy and/or increased risk of drug toxicity.
• Rifampin based TB treatment with Efavirenz based ART is the
preferred treatment approach for HIV-associated TB.
• All HIV-infected patients taking INH should also take
pyridoxine supplementation to decrease the risk of peripheral
neuropathy,
101

55. Initiation of Anti TB in HIV patients already
on ART
• Combination TB therapy should be initiated as soon as
possible in the patient who is already on ART.
• If the patient has attained viral suppression and tolerates his
current ART regimen:
• In the patient taking PI-containing ART, the preferred choice
would be rifabutin
• Rifampin is more cost-effective in areas where resources are
limited.
102

56. Initiation of Anti TB in HIV patients already
on ART…
• Co-administration of rifampin and PI-based therapy is not
recommended by the CDC.
• Rifampin induces both CYP3A4 and efflux pump P-
glycoprotein; PIs are substrates of both systems.
• In HIV-infected patients initiating ART, PIs are usually dosed
with the pharmacokinetic enhancer, ritonavir, which boosts
serum drug levels.
• However, even boosted PIs cannot be given with rifampin,
since PI levels are reduced by as much as 95%.
• Rifabutin, rather than rifampin, is recommended when
protease inhibitors are used for HIV therapy.
103

58. Special considerations for drug therapy in
pregnant women include the following:
 Streptomycin should not be used
 Preventive treatment is recommended during pregnancy
 Pregnant women are at increased risk for isoniazid-
induced hepatotoxicity
 Breastfeeding can be continued during preventive
therapy

59. Special considerations for drug therapy in
children include the following:
 In general, the regimens recommended for adults
are also the regimens of choice for infants,
children, and adolescents
 Ethambutol is often avoided in young children
 Although it is no more toxic, ethambutol is often
avoided because it is difficult to assess visual
acuity in children

60. Latent TB
 Treatment of latent TB infection is effective in preventing
active TB disease in persons with positive TST
 6 month-INH monotherapy is most widely used
recommended regimen for LTBI in both adults and children.
 A 3 months of INH plus rifampicin for children <15years or
 a 3-month regimen of weekly Rifapentine plus isoniazid for
both children and adolescents are newly WHO recommended
regimen as alternatives.
 At present, the 6- month Isoniazid treatment regimen is
the most feasible approach in Ethiopia.

61. INH preventive therapy
 IPT for HIV infected population: should be provided to all
HIV-infected individuals who are unlikely to have active TB
irrespective of CD4 count, ART status, pregnancy status or
history of treatment for prior episode of TB before three
years.
 IPT for HIV negative TB exposed under-five children:
 should be administered for under-five asymptomatic children
who are exposed to TB within the past one year (household
contacts of TB cases)

62. INH preventive therapy
 Dosing of INH for IPT: The dose of INH is 300mg/day
for adults and 10mg/kg for children daily administered
for six months.
 It is also advised to co-administered vitamin B-6
(25mg/day) with Isoniazid to prevent INH-induced
peripheral neuropathy,

63. INH preventive therapy
 Contraindications to IPT: Individuals with any one
or more of the following conditions should not receive
IPT:
 Symptoms compatible with tuberculosis even if the
diagnosis isn’t yet confirmed;
 Active hepatitis (chronic or acute);
 Regular and heavy alcohol consumptions;
 Prior allergy or intolerance to Isoniazid and
 symptoms of peripheral neuropathy

64. Treatment of patient with renal failure
• Consult expert, otherwise avoid Streptomycin & Ethambutol.
• The recommended regimen is therefore 2RHZ/4RH.
• Alteration in dosing of antituberculosis agents, particularly EMB
and PZA, is necessary in patients with renal insufficiency.
• Lengthening the dosing interval is preferable over reducing the
dose to optimize peak serum concentrations.
• Administration of all TB drugs immediately after hemodialysis
facilitates DOT (three times weekly) and minimizes premature
removal of the drugs.
112

65. Treatment of patient with renal failure
Drug
Change in
frequency?
Recommended dose and frequency for patients with
CrCl <30 ml/min or for patients receiving intermittent
hemodialysis
Isoniazid No change
300 mg PO once daily, or 900 mg PO three times per
week
Rifampin No change
600 mg PO once daily, or 600 mg PO three times per
week
Pyrazinamide Yes
25-35 mg/kg (IBW) per dose PO three times per week
(NOT daily); max 2.5 g per dose.
Ethambutol Yes
15-25 mg/kg (IBW) per dose PO three times per week
(NOT daily); max 1.6 g per dose
113
• Dosing recommendations for adult patients with reduced renal function
• Standard doses are given unless there is intolerance.
• Monitoring of serum drug concentrations should be considered to ensure
adequate drug absorption without excessive accumulation and to assist in
avoiding toxicity.

66. Treatment of patients with Liver disorder
• Most anti-TB drugs can cause liver damage.
• Do not give Z ; it is the most hepatotoxic anti-TB drug.
• RH plus one or two non-hepatotoxic drugs such as ES can
be used for total treatment duration of eight months.
• If the patient has severe liver damage, an alternative regimen
is HES in the initial phase.
• This should be followed by HE in the continuation phase
within 12 months.
114

67. Hepatic monitoring
• Obtain baseline liver function tests (LFTs)
a. serum transaminase enzymes
– (AST) [normal 0-40 u/l]
– (ALT) [normal 0-40 u/l]
b. alkaline phosphatase [normal 25-115 u/l]
c. Total bilirubin [normal 0.2-1.5 mg/dl]
• Repeated monthly hepatic enzyme measurements in the
following settings:
– Abnormal baseline results
– A drug reaction is suspected
– Liver disease (eg, hepatitis B or C, alcohol abuse)
– Pregnancy and the first three months postpartum
– Combination therapy including pyrazinamide in continuation
phase
115

68. Hepatic monitoring…
• Patients must be educated about the symptoms of hepatic
toxicity, including;
116

69. Hepatotoxicity
• An asymptomatic increase in AST concentration occurs in
nearly 20% of patients treated with the standard four-drug
regimen;
• Asymptomatic aminotransferase elevations resolve
spontaneously.
 In general, antituberculosis agents should be discontinued
– Transaminases >3X the ULN in association with symptoms, or
– 5X the ULN in the absence of symptoms.
• Differential
– Acetaminophen, alcohol, and hepatitis A, B, or C.
117

70. Hepatotoxicity…
Management
• Hold all drugs and obtain LFTs
• Hold drugs until symptoms resolve and the transaminases decreases to
< 2x normal /or normal.
• Wait for an extra 2 weeks after the resolution of jaundice and upper
abdominal tenderness before recommencing TB treatment.
• Re-challenge the patient after resolution of signs and symptoms by
adding drugs to the regimen every 4 days:
• RE should be restarted first.
• If there is no increase in hepatic transaminases after one week, INH
may be restarted. 118

71. Hepatotoxicity…
• If signs and symptoms recur with re-challenge, discontinue the
responsible drug and modify the regimen and/or duration of therapy
as required
• For those who have experienced prolonged or severe hepatotoxicity,
but tolerate reintroduction with RIF and INH, rechallenge with PZA
may be hazardous.
• In this circumstance, PZA may be permanently discontinued, with
treatment extended to 9 months.
• If AST & ALT are >3X ULN before the initiation of treatment,
– Recommended regimens are 2SERH/6RH, 9RHE or 2SEH/10EH.
• The more unstable or severe liver disease, the fewer hepatotoxic drugs
should be used.
119

72. Hepatotoxicity…
• For patients developing drug-induced hepatitis while on
FDCs.
• When hepatitis with jaundice occurs during the intensive
phase of TB treatment with RHZE:
– Once hepatitis has resolved, restart the same drugs EXCEPT
replace pyrazinamide with streptomycin to complete the 2-month
course of initial therapy, followed by 6EH. (-SRHE/6RH).
• When hepatitis with jaundice occurs during the continuation
phase:
– Once hepatitis has resolved, restart isoniazid and rifampicin to
complete the 4-month continuation phase of therapy.
120

73. Pyridoxine
All patients who are at risk for neuropathy (HIV,
diabetes, renal failure and malnutrition), pregnant
women, and persons with seizures should receive
pyridoxine 50 mg/day while receiving isoniazid.

74. Adjuvant steroid therapy
• Corticosteroids in moderate to severe
tuberculous meningitis appear to reduce
sequelae and prolong survival.
• The mechanism for this benefit is likely owing
to reduction of intracranial pressure.

75. Tuberculosis meningitis
 Dexamethasone: six weeks
 A total dose of 8mg/day for children weighing less than 25
kg and
 12mg/day for adults and children weighing 25 kg or more.
 The initial dose is given for 3 weeks and then decreased
gradually during the following 3-4weeks.
 Prednisolone:
 A dose of 2-4mg/day for children;
 60mg/day for adults for 3 weeks, then tapered gradually
over the following three weeks.
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76. Tuberculosis pericarditis
• Corticosteroids are recommended as adjunctive therapy
for the first 11 weeks of anti-tuberculosis therapy.
• Dose of corticosteroid adjuvant therapy for pericardial TB
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• Children should be treated with doses proportionate to their weight, beginning
with about 1 mg/kg body weight and decreasing the dose as described for adults.

77. Monitoring TB Patient’s Progress
• Monitoring of patient’s progress involves:
• Signs and symptoms or clinical assessment;
• Weight measurement:
• Follow-up AFB sputum examinations for PTB+ cases:
– at 2nd, 5th and 6th for new, and
– at 3rd, 5th, and 8th for retreatment patients
N.B: The sputum sample for the AFB monitoring tests should
be requested during the last week of the indicated months.
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79. 10Q!