Management of Adverse Effects
of Anti-TB drugs (part I)
Dr. Ashraf Abdulhaseeb
Chest Diseases Consultant
Chief of DR-TB center, Abbassia Chest Hospital
1
Presentation outline:
• Monitoring adverse effects
• Main adverse effects and suspected drugs.
• General considerations of adverse effects
management.
• Commonly used ancillary drugs.
2
Monitoring of adverse effects:
Aims at:
• Early detect and treat adverse effects
• Prevent /minimize toxic effects or organ
damage
3
Monitoring should consider the
following factors:
• Patient factors:
•
•
•
•
Age,
initial clinical condition,
HIV testing,
Socioeconomic condition
• Providers:
• trained and alert to early detect adverse effects
• Specialists and consultants in referral centers are
available.
4
Monitoring schedule
I) Initial pretreatment screening and evaluation:
 Initial evaluation serves to:
 Establish a baseline clinical view of the patient
 identify patients who are at increased risk for adverse
effects or poor outcomes.
5
Initial pretreatment monitoring
includes:
1. Thorough medical history and physical examination.
2. History of concomitant conditions which can
contribute occurrence of drug intolerance
3. History of adverse drug reactions.
4. History of allergic reactions
5. Complete blood count
6. Liver functions:
 Total serum Bilirubin
 SGPT & SGOT
 Total serum albumin, total serum protein and A/G ratio.
6
7. Serum Creatinine, blood urea, complete urine
analysis with estimation of total urine protein
content
8. Serum uric acid.
9. Fasting and PP blood sugar.
9. Pregnancy test.
10. Initial chest x-ray
11. Visual acuity, color vision
12. Audiometry
13. Direct smear examination
14. DST for first and second line anti-TB drugs.
7
II) Lab investigation schedule during treatment to
monitor adverse effects
Weight
monthly to adjust doses.
Urea & Serum creatinine monthly while receiving injectable drugs then
quarterly. Risk group patients may need more frequent
testing e.g. elder, patients with renal troubles.
Serum electrolytes
Monthly while receiving injectable drugs then
quarterly, may be more frequent in risk group patients
e.g. elder, vomiting & diarrhea
TSH
Every 6 months if receiving ethionamide /
prothionamide or PAS and monitor monthly for signs
and symptoms of hypothyroidism.
Liver enzymes
Periodic monitoring (every 1month) in patients
receiving Pyrazinamide for extended periods or for
patients at risk for or with symptoms of hepatitis.
Audiometry
Monthly while receiving the injectable drug
Visual acuity & color
discrimination
CBC
Monthly
Monthly
8
II) Lab investigation schedule during treatment to
monitor adverse effects, cont.
Hemoglobin and WBC
Lipase
If on linezolid, monitor weekly at first, then monthly
Indicated for work up of abdominal pain to rule out
pancreatitis in patients on linezolid
Lactic acidosis
Indicated for work up of lactic acidosis in patients on
linezolid or ART
If receiving gatifloxacin, monitor glucose frequently
(weekly) and educate patient on signs and symptoms
of hypoglycaemia and hyperglcycaemia
Serum glucose
9
Monitoring of adverse effects should also
include:
1. In high risk patients (over 50 years, renal
insufficiency, DM, HIV, underweight),
creatinine should be evaluated every week or
every other week for at least the first month of
treatment.
2. Creatinine clearance may be needed for high risk
group patients.
3. If Serum potassium is low, check the
Magnesium and Calcium levels.
10
Special attention should be paid for:
 Liver toxicity.
 Vestibular and hearing toxicity with injectable
drugs.
 Psychiatric disorders with Cycloserine.
 Allergic reactions.
 Hematological changes.
11
Recording the adverse effects in
patient file:
Patient name__________________________________ Patient ID____________________
TB registrations number ___________________________________________________
Description of
the
adverse
reaction
Date
Change
Date
Severity
Of
treatment
treatment
*
change
if made
Other actions
Outcome
**
Severity code:
*1=asymptomatic 2=does not affect daily activities 3=limits daily activities 4=life
threatening hospitalization
Outcome code:
**1= complete resolution 2= partial resolution 3 = no change 4 = worse
comments:_______________________________________________________________
12
13
Renal failure
8% 7% 6%
6% 5% 5% 4%
Optic neuritis
Hepatitis
Gynaecomastia
constipation
Convulsions
Dizziness
Hearing defect
10%
Headache
Sleep disturbance
Skin rash
Allergy
Psychosis
20%
Arthritis
25%
Nausea
30%
Electrolyte disturbance
50%
Depression
70%
Vomiting
73%
Hypothyroidism
Diarrhea
60%
Peripheral neuritis
Gastritis
Side effects
Percent of patient
80%
Adverse effects in cohort 127 patients, Egypt 2009
57%
53%
46%
40%
32%
23% 22%
20%
13% 13% 13% 12%
2%
0%
14
Common adverse effects and suspected drugs
Adverse effects
Suspected drugs
Seizures
Cycloserine & less frequently Isoniazid, Fluoroquinolone
Peripheral neuritis
Cycloserine, Isoniazid & less frequently, Streptomycin,
Amikacin, Kanamycin, Capromycin, Viomycin,
Fluoroquinlones, Prothionamide/Ethionamide,
Linedazole
Hearing loss and
vestibular disturbance
All Aminoglycosides, Capreomycin & less frequently
clarithromycin
Psychotic symptoms
Cycloserine, Fluoroquinolones, Isoniazid,
Prothionamide/Ethionamide
Depression
Maybe due the disease condition of the patient or drugs
Cycloserine & less frequently Fluoroquinolones, Isoniazid,
Prothionamide/Ethionamide
Hypothyrodism
Prothionamide/Ethionamide, PAS
Nausea and vomiting
PAS, Prothionamide/Ethionamide, Pyrazinamid & less
frequently Ethambutol, Isoniazid,
15
Common adverse effects and suspected drugs,
cont.
Adverse effects
Suspected drugs
Gastritis
PAS, Prothionamide/Ethionamide, Pyrazinamid
Hepatitis
Pyrazinamid, Isoniazid, Rifampicin & less frequently
Fluoroquinolones, Prothionamide/Ethionamide
Renal toxicity
All Aminoglycosides, Capreomycin
Electrolyte disturbance
Capreomycin and Viomycin & less frequently Streptomycin,
Kanamycin and Amikacin
Optic neuritis
Mainly Ethambutol & less frequently Prothionamid/Ethionamid
Arthralgia
Mainly Pyrazinamid & less frequently Fluoroquinolones
16
Classification of Adverse Effects
Allergic and dermatological:
Mild
Skin pigmentations
Photo-sensitivity
Dry skin
Moderate to severe
Hypersensitivity
Fever
Rash
Purpura
Allergic dermatitis
Exfoliative dermatitis
Anaphylaxis /Angiodema
17
Classification of Adverse Effects
Gastrointestinal:
Mild
Nausea/Vomiting
Anorexia
Metallic taste/salivation
Stomatitis /Glossitis
Diarrhea
Bloating
Abdominal cramps
Moderate to severe
Gastritis
Gastric ulcer
Hepatitis
18
Classification of Adverse Effects
Neurological and Psychiatric:
Mild
Dizziness
Headache
Fatigue
Somnolence
Insomnia
Irritability
Anxiety
Moderate to severe
Seizure
Peripheral neuropathy
VIII nerve damage: hearing loss,
vestibular impairment
Psychosis
Suicidal tendency
Depression
Confusion
Behavior changes
19
Classification of Adverse Effects
Fluid and electrolyte disturbance &others:
Mild
Myalgia
Cramps
Arthralgia
Candidiasis, stomatitis
Moderate to severe
Electrolyte disturbances
Dehydration
Renal failure
Optic neuritis
Anemia
20
Classification of Adverse Effects
Endocrine adverse effects:
Mild
Changes in menstrual cycle
Gynecomastia
Impotence
Moderate to severe
Uncontrolled diabetes
Hypothyroidism
21
Management of adverse effects
General considerations:
 majority of adverse effects are easy to recognize.
 have a systematic method of patient interviewing
to early detect.
 Proper management of adverse effects begins
with patient education. Inform the patient to
report adverse effects.
 Monthly evaluation by a physician during
ambulatory treatment
22
General considerations, cont.
 DOT workers should be trained to screen
patients for adverse effects.
 Scheduled laboratory screening to detect
occult adverse effects e.g. nephrotoxicity.
 Electrolyte disturbance is generally a late
effect occurring after months of starting
treatment.
 Complete discontinuation of therapy because
of adverse effects is rare.
23
General considerations, cont.
 Mild adverse effect is or not dangerous,
continue the treatment regimen, with the
help of ancillary drugs if needed.
 Some adverse effects may disappear or
diminish with time, and patients may be able
to continue receiving the drug if sufficiently
motivated.
 adverse effects of a number of second-line
drugs are highly dose dependent, reducing the
dosage of the offending drug is another
method of managing adverse effects
24
General considerations, cont.
 Pyridoxine (vitamin B6) should be given to all
patients receiving cycloserine or terizidone to
help prevent neurological adverse effects.
Recommended dose is dose is 50 mg for every
250 mg of cycloserine
 Psychosocial support is an important
component of the management of adverse
effects.
25
General considerations, cont.
 Psychosocial support is an important
component of the management of adverse
effects. A stock of these drugs should be
always available.
 Timely and intensive monitoring for, and
management of, adverse effects caused by
second-line drugs are essential components of
DR-TB control program.
26
Commonly used ancillary medications
Nausea, vomiting, Metoclopramide, prochlorperazine,
upset stomach
promethazine
Heartburn, acid
indigestion, sour
stomach, ulcer
H2-blockers (ranitidine, famotidine, etc.),
proton pump inhibitors (omeprazole etc.)
Avoid antacids because they can decrease
absorption of Flouroquinolones
Oral candidiasis
Fluconazole, clotrimazole lozenges ..etc
(non-AIDS patient)
Diarrhoea
Depression
Loperamide or other anti-diarrheal
Selective serotonin reuptake inhibitors
(fluoxetine, sertraline), tricyclic
antidepressants (amitriptyline)
27
Commonly used ancillary medications
Prophylaxis of neurological
complications of
Pyridoxine (vitamin B6)
cycloserine
Peripheral neuropathy
Amitriptyline
Meclizine, dimenhydrinate,
vestibular symptoms
prochlorperazine, promethazine
Musculoskeletal pain,
Ibuprofen, paracetamol
arthralgia, headaches
Cutaneous reactions,
Hydrocortisone cream, calamine,
itching
caladryl lotions
Antihistamines (diphenhydramine,
Systemic hypersensitivity chlorpheniramine, dimenhydrinate),
reactions
corticosteroids (prednisone,
dexamethasone)
28
Commonly used ancillary medications
Bronchospasm
Inhaled beta-agonists (albuterol, etc.),
inhaled corticosteroids
(beclomethasone, etc.), oral steroids
(prednisone), injectable steroids
(dexamethasone, methylprednisolone)
Hypothyroidism
Levothyroxine
Electrolyte wasting
Potassium and magnesium
replacement
29
Commonly used ancillary medications
Severe anxiety
Lorazepam, diazepam, clonazepam
Insomnia
Dimenhydrinate
Psychosis
Haloperidol, thorazine, risperidone
(consider benzotropine or biperiden to
prevent extrapyramidal effects)
Seizures
Phenytoin, carbamazepine,
phenobarbital
30
Thank you
31