Handbook on Adverse Drug Reactions in TB Treatment Rajendra Prasad, Nikhil Gupta
INDEX
ABCDEFGHIJKLMNOPQRSTUVWZ
A
Abacavir 150
Abscesses 16
Acneiform eruption 56
Acquired immunodeficiency syndromes 149
Acyclovir 85, 88
Adefovir 88
Adverse drug reactions, epidemiology of 163, 179
Aggression 23, 26
Agranulocytosis 10, 14, 54
Alcohol 86, 89
dependence 139
excessive concurrent use of 23
Allergic reactions 27, 29, 31, 32, 42, 57, 58, 152
Allergy 27
Allopurinol 75, 83, 88
Alopecia 57
Aluminium hydroxide 81
American Academy of Pediatrics 17
American Thoracic Society 91, 94
Amikacin 2–4, 18, 56, 64, 85, 88, 93, 117, 147
drug interactions of 69
sulfate 18
Aminoglycosides 16–20, 85
coadministration of 69
Amiodarone 82
Amoxicillin 4, 46, 47, 59, 75, 94, 113, 118
clavulanic acid, drug interactions of 74
Amoxyclav 88
Amphotericin 69, 70, 83, 85, 88
Amprenavir 151
Analgesics 82
Anemia 10, 37, 44, 53, 59
aplastic 54
hemolytic 14, 53, 54
sideroblastic 53
Anorexia 25, 27, 36, 56–58, 102
Antacids 65–67, 70–74, 76, 77, 79, 81, 83, 85–88
Anticoagulants 86
Anticonvulsants 82
Antidepressants 87
Antipsychotics 82
Antiretroviral drug 149, 153
interactions 149, 155
Antiretroviral therapy 149, 157
adverse drug reactions of 157
Antitubercular drugs 1, 55, 81, 85, 135, 153
adverse drug reactions of 53, 56
doses of 1, 2
drug interactions of 65, 69
interactions 149
management strategies of 60, 144
pharmacology of 9, 16
regimen 1, 4
Antituberculosis
therapy 157
adverse drug reactions of 157
treatment 98
Anxiety 23, 24, 29, 31, 33, 35, 57
severe 23
Appetite, loss of 40, 49, 59, 150
Arrhythmias, ventricular 59
Arthralgia 25, 38, 53, 57, 64, 147, 161, 174
Ascitic fluid 16
Aspirin 27
Astemizole 88
Ataxia 10, 19
Atazanavir 151
Atracurium 69, 88
Audiometry 140
Auditory nerve
damage 54
impairment 14
Azole antifungal
agents 89
drugs 89
Azotemia 21
B
Bactericidal drug 14
Barbiturates 82
Bedaquiline 3, 48, 59, 64, 89, 94, 118, 147
drug interactions of 77
plasma protein binding of 48
Benzodiazepines 81, 82
Beta-lactam antibiotics 43
Bile 35
Bone marrow
depression 37, 59
suppression 160
Breastfeeding 17, 19, 21, 23, 25, 27, 28, 30, 32, 34, 35, 37–39, 41, 43–45, 47, 48, 50
British Thoracic Society 94
Bumetanide 69
Burning 36, 54
C
Calcium 21, 33
high concentration of 85
serum 140
Candida stomatitis 59
Capreomycin 2–4, 20, 56, 64, 85, 93, 113, 117, 147
drug interactions of 70
sulfate 20
Carbamazepine 81, 89
Carbapenem 45
intolerance 45, 46
Carboplatin 88
Carbothionamides 24
Central nervous system 29
toxicity 157
Cephalosporins 85
Cerebrospinal fluid 9
Cervical lymphadenopathy, tubercular 100
Chest
pain 49, 51
radiograph 140
X-rays 123, 125–127, 129, 130, 132, 133
Chills 22, 39
Cidofovir 69, 70
Cilastatin 2–4, 43, 44, 59, 77, 88, 94, 118
Cisapride 88
Cisplatin 85
Citric acid 87
Clarithromycin 2, 4, 42, 59, 64, 88, 93, 117, 147
drug interactions of 77
Clavulanate 3, 4, 46, 47, 59, 75, 113
Clavulanic acid 94, 118
Clofazimine 2–4, 35, 36, 56, 64, 87, 89, 93, 95, 107, 117, 136 147
drug interactions of 76
Clostridium difficile colitis 42
Cochlear ototoxicity 19, 56, 57
Colchicine 83
Colitis
hemorrhagic 59
pseudomembranous 44, 53, 59
Complete blood count 41
Confusion 12, 23, 24, 26, 29, 31, 33, 35, 55, 57
Contraception 114
Contraceptives 82
Corticosteroids 81, 82, 87
Cough 102, 153
Cramps 36
Cyclic polypeptide 20
Cycloserine 2–4, 22, 23, 57, 64, 81, 86, 93, 107, 113, 117, 147
doses of 23
drug interactions of 70
Cyclosporine 82, 83, 85, 86, 88
D
Dapsone 82, 86
Darunavir 151
Deafness, congenital 17, 20
Deep intramuscular injection 18
Delamanid 3, 49, 59, 64, 89, 94, 118, 117
drug interactions of 78
Delavirdine 151
Depression 23–26, 36, 57, 61, 145, 151, 157
Dermatitis, exfoliative 11, 37, 59
Diabetes
control, loss of 13
mellitus 116, 139
Diarrhea 25, 27, 29, 31–36, 42, 44, 46, 47, 57, 58, 59, 151–153, 158
bloody 46
severe 42, 43, 46, 47
watery 46
Diarylquinoline 48
Diazepam 81
Didanosine 33, 150
Digoxin 82, 86, 88
Diltiazem 82
Directly observed treatment short course 95, 110
Distress, epigastric 10
Disulfiram 81
Dizziness 10, 58, 12, 18, 23, 25, 26, 29, 31–35, 51, 55, 58, 59, 152
Dolutegravir 152
Drowsiness 23, 25, 54, 57, 151
Drug resistant tuberculosis 139
Drug susceptibility testing 106, 115, 137
Dry mouth 150
Dry skin 36, 56
Duloxetine 87
Dysarthria 53
Dysglycemia 34, 58, 161
Dysphoria 53, 151
E
Efavirenz 78, 82, 89, 151
Electrocardiography 141
Electrolyte
abnormalities 21, 54
disturbances 19, 56, 63, 147, 160
Eletriptan 87
Elvitegravir 152
Emtricitabine 150
Enalapril 82
Enflurane 81
Enfuvirtide 152
Eosinophilia 10, 19, 56
Ephedrine 76
Epilepsy 23
Ethacrynic acid 69, 83, 85
Ethambutol 1, 3–5, 9, 11, 12, 53, 55, 64, 67, 83, 93, 100, 102, 117, 122, 126, 136, 147, 163, 174
drug interactions of 67
overdosage of 12
Ethionamide 2–4, 24, 27, 57, 58, 64, 82, 83, 86, 87, 93, 107, 117, 147
drug interactions of 70
Etravirine 151
Euphoria 10
Extensively drug resistant tuberculosis, treatment of 112
Extracellular fluid 16
Eyes, yellow 29, 31, 33, 35, 36, 39, 4
F
Fainting 49, 51
Fat redistribution 151, 152
Fatigue 150
Fatigueness 153
Fever 11, 13, 22, 27, 39, 40, 56–58, 102, 150
Fine-needle aspiration cytology 100
First-line antituberculosis drugs 165
Fluconazole 82
Flue-like syndrome 53
Fluoroquinolones 2, 28, 29, 31, 33, 64, 85, 89, 113, 147
intolerance of 33, 34
Fluoxetine 87
Fosamprenavir 151
Foscarnet 69, 70
Furosemide 69, 85
Fusion inhibitors 152
G
Gallamine triethiodide 69
Gallbladder 28, 35
Gastric lavage 11, 12, 13
Gastritis 62, 146
Gastrointestinal
distress 49, 59
disturbances 24
intolerance 27, 29, 31, 32, 34, 37, 57–59
reaction 53
upset 11–13, 41, 54
Gatifloxacin 2, 33, 34, 58, 93, 117, 136
doses of 34
Gentamicin 88
Glomerular filtration 12, 14, 28
Glucose
monitoring 34
serum 140
Glutaryl pyruvate transaminase 96
Glycemic control 34
Granulocytopenia 150
Gums, inflammation of 23, 57
Gynecomastia 10, 25, 57
H
Hallucinations 12
Haloperidol 82
Headache 23–25, 29, 31, 32, 34, 42, 49, 57–59, 87, 150–153, 158
Hearing loss 42, 54, 61, 144
Hemoglobin 140
Hemorrhage, intracranial 152
Hepatic
disease 17, 19, 25, 29, 30, 36, 38, 40, 41, 43–45, 47, 49, 50
dysfunction 13
injury 59
insufficiency, severe 36
Hepatitis 10, 11, 13, 27, 37, 53, 56–59, 63, 97, 146, 153
drug induced 55
Hepatotoxicity 38, 40, 53, 159, 171
drug induced 96
Highly active antiretroviral therapy 149
Human immunodeficiency virus 139, 140, 149
treatment of 149
Hydrolysis, enzymatic 9
Hyperbilirubinemia, indirect 151
Hyperglycemia 34, 151, 152
signs of 35
Hyperlipidemia 160
Hypersensitivity 13, 47, 56, 57
reaction 10–12, 14, 40, 54, 59, 150, 152
Hyperuricemia 12, 13, 174
Hypocalcemia 54, 56
Hypoglycemia 26, 34
signs of 35
Hypokalemia 19, 54, 56, 63, 147
Hypomagnesemia 19, 54, 56, 63, 147
Hypotension 44, 59
postural 25, 57
Hypothyroidism 25, 27, 57, 58, 62, 146, 161
I
Ichthyosis 36, 56
Imipenem 2–4, 43, 44, 59, 77, 88, 94, 118
Indinavir 82, 151
Influenza-like syndrome 11
Insomnia 29, 31, 32, 34, 58, 150
International Union Against Tuberculosis and Lung Disease 91
Intrathoracic lymph node tuberculosis 4
Intrauterine devices 115
Iris 33, 152
Isoniazid 1, 4, 5, 7–13, 53, 54, 64, 65, 67, 81–83, 86, 87, 91, 93, 100, 102, 105, 117, 118, 122, 126, 135, 136, 147, 155, 163
drug interactions of 65
high dose 2–4, 94, 118, 136
overdosage of 10
plus pyrazinamide 11
Isonicotinic acid, hydrazide of 9
Itraconazole 82, 89
J
Jaundice 10, 23, 25, 55, 57
Joint pain 29, 31, 33, 35, 49, 54, 59, 153
Joint Tuberculosis Committee of British Thoracic Society 98
K
Kanamycin 2–4, 16, 17, 19, 20, 57, 64, 85, 88, 93, 103, 117, 124, 130, 136, 147, 180
drug interactions of 69
sulfate 16
Ketoconazole 81–83, 89
Kidneys 28
L
Lactation 139
Lactic acidosis 140, 150, 159
Lamivudine 150
Leukopenia 25, 38, 57, 59
Levodopa 81
Levofloxacin 2, 4, 28, 58, 93, 117
doses of 29
drug interactions of 72
Linezolid 2–4, 40, 59, 64, 87, 93, 107, 117, 147
drug interactions of 75
Lipase 140
Lipodystrophy 160
Liver 28
cirrhosis of 103
disease 45
acute 139
chronic 139
pre-existing 98
severe 51
disorders 118
failure, acute 172
function
monitoring 38, 40
test 26, 27, 32, 34, 58, 150–152
serum enzymes 140
toxicity 42
Lopinavir 78, 82, 151
Lung 28
Lupoid reaction 53
Lymphadenitis, tuberculous peripheral 4
Lymphatic fluid 16
M
Macrolide 89
antibiotic 42
Maculopapular rash 21, 56
Magnesium 21, 33
antioxidants 87
serum 140
Malabsorption syndrome 27, 58
Malaise 29, 31, 32, 34, 40, 58, 150
Maraviroc 153
Medical termination of pregnancy 113
Medroxyprogesterone 115
Memory, loss of 24
Meningitis 44, 45
tubercular 4
Mental illness 139
Meropenem 3, 45, 59, 94, 118
Methadone 82
Methotrexate 85
Methylphenidate 76
Migraine 87
Mirtazapine 87
Morphine 82
Moxifloxacin 2, 4, 29, 30, 31, 58, 93, 117, 136
drug interactions of 73
Multidrug resistant tuberculosis 64, 105, 112, 135, 179
treatment of 112, 122
Muscle
pain 153
relaxants, non-depolarizing 69
twitching 18, 20
weakness 18, 20, 22
Myasthenia gravis 14
Mycobacterium tuberculosis 102, 103, 105, 122, 124, 129–131, 135, 141
Myopathy 150
N
Narcotics 82
Nausea 10, 11, 19, 25–27, 36, 39, 40, 42, 44, 46, 47, 49, 51, 57, 59, 62, 146, 150–153, 158
Nelfinavir 82, 151
Nephrolithiasis 151, 159
Nephrotoxic agents 69, 70
Nephrotoxicity 14, 17, 19, 21, 54, 56, 57
Neuritis
peripheral 10, 53, 57
retrobulbar 53, 173
Neuropathy, symptoms of 41
Neurotoxicity 25, 56
Nevirapine 78, 151
Nifedipine 82
Nightmares 23
Nitrodihydro-imidazo-oxazole 49
Non-nucleoside reverse transcriptase inhibitors 149, 150, 151, 154, 155
Nonsteroidal anti-inflammatory drugs 85, 86
Nucleoside reverse transcriptase inhibitors 149, 150, 154
Nystagmus 19, 55
O
Ofloxacin 2, 31, 32, 58, 93, 117
doses of 32
drug interactions of 73
Ondansetron 89
Optic
neuritis 41, 53, 57, 63, 147, 160
neuropathy 41, 59
Oral
absorption 18, 21, 22, 24, 26, 28, 30, 32, 33, 35, 38, 39, 41, 45, 47, 48, 50
anticoagulants 74, 81, 82, 85, 88
bacteriostatic second line drugs 2
contraceptives 75, 88
hypoglycemic agents 82
paresthesias 151
ulcers 150
Ototoxicity 14, 21, 37, 59, 67, 173
Oxazolidinones 41
P
Pain 18, 20, 21, 29, 31, 33, 35, 42, 54
abdominal 11, 25, 36, 42, 49, 56, 57, 59, 152, 158
eye 23, 39, 57
severe abdominal 27
Pale skin 23, 57
Pancreatitis 49, 150, 158
Pancuronium 69, 88
Para-aminosalicylic acid 2, 4, 5, 25, 26, 64, 65, 82, 86, 97, 102, 113, 147
drug interactions of 71
Paracetamol 81
Parkinson's disease 76
Paroxetine 87
Pellagra 53, 57
Penicillins 69, 70
Pentamidine 88
Pericardial fluid 16
Peripheral neuropathy 17, 19, 29, 33, 41, 54, 56–60, 144, 150, 157, 172
Peritoneal fluid 16
Phagocytic cells 28
Phenazine derivative 35
Phenytoin 81, 82, 86
Phospholipidosis 49
Phospholipids, accumulation of 49
Photosensitivity 29, 31, 32, 34, 53, 57, 58
Phototoxicity 56
Pneumonia, bacterial 152
Polymyxins 85
Porphyria 25
Potassium 21
serum 140
Pregnancy 17, 19, 21, 23, 25, 27–39, 41, 43–45, 47, 48, 50, 139
Probenecid 67, 74, 86–88
Propafenone 82
Prostatic tissue 28
Protease inhibitors 149, 151, 154
Proteinuria 19, 21, 56
Prothionamide 2–4, 24, 57, 64, 86, 107, 136, 147
drug interactions of 70
Prothrombin time 58
Pruritus 40, 152
Pseudoadrenal crisis 53
Pseudojaundice 38, 59
Psychiatric disorder 172
Psychiatric disturbances 10, 57
Psychosis 10, 23, 120
Psychotic disturbances 25
Pulmonary tuberculosis 101, 103, 122, 124
Pyrazinamide 1, 3–5, 7, 9, 13, 53–55, 64, 82, 83, 92, 93, 100, 102, 108, 117, 118, 122, 126, 130, 136, 147, 163, 174, 175
drug interactions of 67
overdosage of 13
Pyridoxine 88
administration of 25
Q
Quinidine 82
R
Raltegravir 152
Ranitidine 81
Rash 10–13, 17–20, 22, 24, 29, 31, 33, 34, 37, 38, 40, 41, 43, 47, 56–59, 150–152
Refabutin 59
Renal disease 10–14, 17, 19, 21, 23, 25, 27, 29, 30, 32, 34, 35, 37–39, 41, 43, 44, 45, 47, 48, 50
Renal failure 14, 53, 59
Renal insufficiency 23, 116, 139
Renal toxicity 63, 147, 159, 175
Restlessness 23, 29, 34, 57, 58
Reverse transcriptase inhibitors 149
Revised National Tuberculosis Control Program 3, 164
Rifabutin 1, 4, 37, 38, 40, 91, 93, 117
Rifampicin 1, 4, 5, 7, 9–11, 13, 53–55, 64, 66, 67, 81, 83, 87, 89, 92, 93, 100, 102, 105, 117, 118, 122, 126, 135, 147, 163
drug interactions of 66
overdosage of 11
resistant tuberculosis 105, 135
Rifamycins 37–40, 153, 154
Rifapentine 39, 91, 93, 117
Ritonavir 78, 82, 89, 151, 152
Rocuronium 88
S
Salicylic acid 26
Saquinavir 82, 152
Seizure 24, 44, 46, 53, 57, 60, 59, 119, 144
Shock 55
anaphylactic 54
Sinuses, mucosa of 30
Skeletal muscle 30
Skin
blister fluid 30
discoloration 38, 59
rash 23, 27, 46, 53, 55, 57, 151, 159
reactions 53
yellow 26, 29, 31, 33, 35, 36
Sleep disturbances 23, 57
Sodium picosulfate 87
Sore throat 39
Speech, slurring of 10
Spleen 35
Statins 82
Stavudine 150
Steatorrhea 58
Steatosis 150
Stevens-Johnson syndrome 37, 59
Stomatitis 25, 57
Streptomyces
cattleya 43
griseus 14
mediterranei 10
Streptomycin 1–5, 7, 8, 14, 17, 19, 20, 54, 55, 64, 67, 85, 88, 91, 93, 117, 126, 147, 163, 173
drug interactions of 67
nephrotoxicity of 67
overdosage of 15
sulfate 14
Sucralfate 33, 85
Sulfonamides 82
Sulfonylurea 86, 87
Sumatriptan 87
Swelling 18, 20, 29, 31, 33, 35, 47
face 20, 46
joints 39, 40
lips 46
throat 46
Synovial fluid 16
T
Tachycardia 59
Tendon rupture 29, 31, 33, 34, 58
Tenofovir 150
Terfinadine 88
Terizidone 2–4, 22, 86, 93, 107, 117
drug interactions of 70
Theophylline 81, 82, 86
Thiacetazone 4, 5, 7, 8, 36, 55, 59, 85
Thionamides 25
doses of 25
Thiosemicarbazone 36
Thrombocytopenia 10–14, 38, 53, 54, 57, 59
Thrombophlebitis 44, 59
Thyroid
disease 139
enlargement 27, 58
stimulating hormone 140, 143
Tipranavir 152
Tobramycin 88
Topoisomerase 28
Torasemide 69
Toxic encephalopathy 10
Trazodone 87
Tremors 57
Tricyclic antidepressants 82
Trouble breathing 18, 20, 22, 46, 47
Tuberculosis 9, 16, 56, 65, 69, 149, 163
duration of treatment in 7
extensively drug resistant 112
in lactation, treatment of 91, 100
in liver diseases, treatment of 91, 96, 100, 102
in pregnancy, treatment of 91, 100
in renal insufficiency, treatment of 91, 93, 100, 101
osteoarticular 4
treatment of 5, 91, 93, 96
Tubocurarine 69
Tubular dysfunction 21, 56
Typhoid vaccine 88
U
Urinary retention 10
Urine 28
Urticaria 21, 56
Uveitis, anterior 38, 59
V
Vaginitis 59
Valproic acid 81, 88
Vancomycin 85, 88
Vasculitis 10, 53
Venlafaxine 87
Verapamil 82
Vertigo 19
Viral hepatitis 103
Vision tests 141
Vision, blurring of 10
Visual impairment 55
Vitamin 33
B12 87
B6 41, 86
Vomiting 10, 11, 19, 25–27, 36, 39, 40, 42, 44, 46, 47, 49, 51, 55, 57, 59, 62, 146, 150–152, 158
W
Wheezing 46
White blood count 140
Z
Zalcitabine 150
Zidovudine 82, 150
Zinc 33
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Chapter Notes

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Antitubercular Drug Doses and Regimens for Adults and ChildrenCHAPTER 1

Antitubercular drugs with their doses used in new and previously treated patients of tuberculosis are tabulated in Tables 1.1, 1.2 and 1.3.
TABLE 1.1   Dose of antitubercular drugs used in new patients of tuberculosis.
Drugs
Daily
Intermittent
Adult
Children*
3-weekly
2-weekly
H
5
(4–6)
10
(10–15)
10
(8–12)
15
(13–17)
R
10
(8–12)
15
(10–20)
10
(8–12)
10
(8–12)
Z
25
(20–30)
35
(30–40)
35
(30–40)
50
(40–60)
E
15
(15–20)
20
(15–25)
30
(25–35)
45
(40–50)
S
15
(12–18)
15
(12–18)
15
(12–18)
15
(12–18)
*Doses modified in 2008. (H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol, S: streptomycin).
TABLE 1.2   Doses of antitubercular drugs used in previously treated tuberculosis patients
Drugs
Average daily dosage
Daily dosage (mg)
Type of anti- mycobacterial activity
Minimum
Maximum
Group 1
First line oral agents
Pyrazinamide (Z)
Ethambutol (E)
Rifabutin (Rfb)
 
 
25 mg/kg
15 mg/kg
5–10 mg/kg
 
 
1,200
800
150
 
 
1,500
1,200
600
 
 
Bactericidal
Bacteriostatic
Bactericidal2
Group 2
Injectable agents
Kanamycin (Km)
Amikacin (Am)
Streptomycin (S)
Capreomycin (Cm)
 
 
15 mg/kg
15 mg/kg
15 mg/kg
15 mg/kg
 
 
750
750
750
750
 
 
1,000
1,000
1,000
1,000
 
 
Bactericidal against actively multiplying organisms
Group 3
Oral bacteriostatic second line drugs
Ethionamide (Eto)
Prothionamide (Pto)
Para-aminosalicylic acid (PAS)
Cycloserine (Cs)
Terizidone (Trd)
 
 
15–20 mg/kg
15–20 mg/kg
200–300 mg/kg
10–20 mg/kg
10–20 mg/kg
 
 
500–750
500–750
10 g
500–750
500–750
 
 
1,000
1,000
12 g
1,000
1,000
Bacteriostatic
Group 4 Fluoroquinolone
Moxifloxacin (Mfx)
Ofloxacin (Ofx)
Levofloxacin (Lfx)
 
7.5–10 mg/kg
15–20 mg/kg
7.5–10 mg/kg
 
400
800
500
 
400
1,000
1,000
Weakly bactericidal
Group 5
Agents with unclear role in treatment of drug resistant TB
Clofazimine (Cfz)
Linezolid (Lzd)
Amoxicillin/clavulanate (Amx/Clv)
Thioacetazone (Thz)
Imipenem/cilastatin
(Ipm/Cln)
High dose isoniazid
(high-dose H)
Clarithromycin (Clr)
 
 
4–5 mg/kg
−
2 g/day
150 mg/day
500–1,000 mg/kg/IV every 6 hourly
16–20 mg/kg
10–15 mg/kg
 
 
100
600
500/125 twice a day
-
500
600
500 twice a day
 
 
300
600
1,000/250 twice a day
-
1,000
900
500 twice a day
 
 
Bacteriostatic
Weakly bactericidal
 
Bactericidal (pH dependent)
TABLE 1.3   Doses of antitubercular drugs used in drug resistant tuberculosis patients (WHO-2016).
Groups
Drugs
Average daily dose
Daily dosage (mg)
Minimum
Maximum
A. Fluoroquinolones
Levofloxacin
Moxifloxacin
Gatifloxacin
7.5–10 mg/kg
7.5–10 mg/kg
7.5–10 mg/kg
750
400
400
1000
400
4003
B. Second line injectable agents
Amikacin
Kanamycin
Capreomycin
Streptomycin
15 mg/kg
15 mg/kg
15 mg/kg
15 mg/kg
500
500
500
500
1,000
1,000
1,000
1,000
C. Other core second line agent
Ethionamide/ prothionamide
Cycloserine/ terizidone
Linezolid
Clofazimine
15–20 mg/kg
10–20 mg/kg
-
4–5 mg/kg
500
500
600
100
1,000
1,000
600
300
D. Add on agents
D1
Pyrazinamide
Ethambutol
High dose isoniazid
25 mg/kg
15 mg/kg
16–20 mg/kg
750
600
600
2,000
1,200
1,500
D2
Bedaquiline
400 mg OD x 2 weeks and then 200 mg 3 times per week
Delamanid
100 mg twice daily
D3
PAS
200–300 mg/kg
10 g
12 g
Imipenem- cilastatin
1,000 mg/1,000 mg twice daily
Meropenem
1,000 mg thrice daily
Amoxicillin-clavulanate
80 mg/kg/day
500/125 mg BD
1000/250 mg BD
Thioacetazone
150 mg once daily
World Health Organization (WHO) recommended treatment regimens for each diagnostic category for adults and children are tabulated in Tables 1.4 and 1.5. Various standard chemotherapy regimens for newly diagnosed patents of tuberculosis by international union against tuberculosis and lung disease are tabulated in Table 1.6. New WHO guideline (2009) for treatment of tuberculosis is tabulated in Table 1.7.
TABLE 1.4   Revised National Tuberculosis Control Program (RNTCP) treatment regimen (Technical and operational guideline for TB control in India 2016).
TB patients
TB treatment regimens
Initial phasea
Continuation phase
New patients
2 HRZEb
4 HRE
Previously treated patients
2 HRZES/1 HRZE
5 HRE
Rifampicin resistant +isoniazid sensitive or unknown
(6–9) Km Z E Eto Cs Lfx H
18 Eto Cs Lfx E H4
Confirmed MDR-TB patients
(6–9) Km Z E Eto Cs Lfx (modify treatment based on the level of INH resistance)c
18 Eto Cs Lfx E
Confirmed XDR-TB patients
(6–12) Cm PAS Mfx High dose-H Cfz Lzd Amx/Clv
18 PAS Mfx High dose-H Cfz Lzd Amx/Clv
(H: isoniazid; Z: pyrazinamide; E: ethambutol; Rfb: rifabutin; Km: kanamycin; Am: amikacin; S: streptomycin; Cm: capreomycin; Mfx: moxifloxacin; Lfx: levofloxacin; Eto: ethionamide; Pto: prothionamide; PAS: para-aminosalicylic acid; Cs: cycloserine; Trd: terizidone; Cfz: clofazimine; Lzd: linezolid; Amx/Clv: amoxicillin/clavulanate; Thz: thiacetazone; Ipm/Cln: imipenem/cilastatin; high-dose H: high dose isoniazid; Clr: clarithromycin) a Direct observation of drug intake is required during the initial phase of treatment in smear-positive cases and always in treatment that includes rifampicin. b In tubercular meningitis (TBM), spinal TB with neurological complications and other hematogenous tuberculosis continuation phase may be extended for 12–24 months based on clinical decision of the treating physician. c For isoniazid resistance, decision of use of isoniazid in the regimen depends on the following:
  • If high level resistance detected by liquid culture — omit INH
  • If low level resistance detected by liquid culture — add high dose of INH
  • If LPA reports INH resistance by Kat G mutation — omit INH
  • If LPA reports INH resistance by INH A mutation — use high dose INH. Ethionamide in the treatment regimen may be replaced with PAS
TABLE 1.5   WHO treatment categories and regimen for children 2014.
TB diagnostic category
Anti-TB drug regimen
Intensive phase
Continuation phase
Low HIV prevalence (and HIV-negative children) and low isoniazid resistance settings
Smear-negative pulmonary TB
Intrathoracic lymph node TB
Tuberculous peripheral lymphadenitis
2 HRZ
4 HR
Extensive pulmonary disease
Smear-positive pulmonary TB
Severe forms of extrapulmonary TB (other than tuberculous meningitis/osteoarticular TB)
2 HRZE
4 HR
High HIV prevalence or high isoniazid resistance or both
Smear-positive PTB
Smear-negative PTB with or without extensive parenchymal disease
All forms of EPTB except tuberculous meningitis and osteoarticular TB
2 HRZE
4 HR
All regions
Tuberculous meningitis and osteoarticular TB
2 HRZE
10 HR
MDR-TB
Individualized regimen
(E: ethambutol; H: isoniazid; R: rifampicin; Z: pyrazinamide)5
TABLE 1.6   Various standard chemotherapy for newly diagnosed patient.
Recommended standard 6-month regimen
  • 2 EHRZ/4 HR
  • 2 HRZ/4 HR
  • 2 SHRZ/4 HR
Variants of standard 6-month regimen (supervised chemotherapy)
  • 2 HRZ/4 H3R3
  • 2 HRZ/4 H2R2
  • 2 E3H3Z3/4 H3R3
  • 2 S3H3R3Z3/4 H3R3
  • 2 E3H3R3Z3/4 H3R3
Alternative less potent regimens of longer duration
  1. With a potent initial 4-drug phase
    • 2 SHRZ/6 HT or 6 HE
    • 2 SHRZ/6 S2H2Z2
  2. With a less potent or no initial phase
    • 2 SHR/7 HR
    • 9 HR
    • 2 SHE/10
    • 12 HT or 12 HE
    • 2 HER/7 HR
    • 2 SHT/10 HT
    • 2 SHP/10 HP
    • 12 S2H2
(S: streptomycin; H: isoniazid; R: rifampicin; Z: pyrazinamide; E: ethambutol; T: thiocetazone; P: para-aminosalicylic acid)
TABLE 1.7   Treatment of TB (WHO 2009 guidelines).
New patient regimen
Retreatment regimen with first line drugs
MDR regimen
  1. Should receive a regimen containing 6 months of rifampicin: 2 HRZE/4 HR
  2. Should receive a regimen containing 6 months of rifampicin along with ethambutol: 2 HRZE/4 HRE where high levels of isoniazid resistance in new TB patients is suspected (presence of resistance to low concentrations of isoniazid (>1% of bacilli resistant to 0.2 µg/mL but susceptible to 1 µg/mL of isoniazid)
  3. Should receive daily TB treatment at least during the intensive phase or for the continuation phase, the optimal dosing frequency is also daily for these TB patients with known positive HIV status and also living in HIV-prevalent settings (defined as countries, subnational administrative units, or selected facilities where the HIV prevalence among adult pregnant women is ≥1% or among TB patients is ≥5%)
  1. TB patients returning after defaulting or relapsing from their first treatment course may receive the retreatment regimen containing first-line drugs 2 HRZES/1 HRZE/5 HRE if country-specific data show low or medium levels of MDR in these patients or if such data are not available
  2. Should receive daily TB treatment rather than intermittent treatment
  1. Use at least 4 drugs certain to be effective
  2. Do not use drugs for which there is the possibility of cross- resistance
  3. Eliminate drugs that are not safe
  4. Include drugs from Groups 1–5 in a hierarchical order based on potency. For further details see chapter on MDR-TB
6
FURTHER READINGS
  1. Companion Handbook to the WHO guidelines for the programmatic management of drug resistant tuberculosis. WHO/HTM/TB/2014.11.
  1. Guidelines for programmatic management of drug resistant tuberculosis. WHO,  2011. WHO/HTM/TB/2011.6
  1. Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008. Geneva, World Health Organization,  2008 (WHO/HTM/TB/2008.402).
  1. International Union Against Tuberculosis and Lung Disease. Management of tuberculosis: a guide for low income countries. Fifth edition. Paris: IUATLD;  2000.
  1. International Union Against Tuberculosis and Lung Diseases. Guidelines for Clinical and Operational Management of Drug-Resistant Tuberculosis. Paris: IUTLD;  2013.
  1. Jindani A, Nunn AJ, Enarson DA. Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: international multicentre randomised trial. Lancet. 2004;364:1244–51.
  1. Management of patients with multidrug resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement. E R J. 2014;44:23–63.
  1. Nahid P, et al. ATS/CDC/IDSA Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infec Dis. 2016:1–50.
  1. Technical and Operational Guidelines for TB Control in India 2016.
  1. Treatment of tuberculosis: guidelines for national programmes, 3rd edition Geneva, World Health Organization,  2003 (WHO/CDS/TB/2003.313).
  1. WHO treatment guidelines for Drug-Resistent Tuberculosis – 2016 Update. WHO/HTM/TB/2016.04.
  1. World Health Organization. Guidance for National Tuberculosis and HIV Programmes on the management of tuberculosis in HIV-infected children: recommendations for a public health approach. Geneva: World Health Organization;  2010.
  1. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children 2006 and 2014.
  1. World Health Organization. Report of the meeting on TB medicines for children-July 2008. World Health Organization,  Geneva; 2008.
  1. World Health Organization. Treatment of TB Guidelines - 4th edition. WHO/HTM/TB/2009.420.