Management of Adverse Effects
of Anti-TB drugs (part II)
Dr. Ahraf Abdulhaseeb
Chest Diseases Consultant
Chief of DR-TB Center, Abbassia Chest Diseases
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I) Management of Gastro-intestinal intolerance
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A. Gastritis
Symptoms: - epigastric pain or burning sensation,
- bitter taste in the mouth,
- less pain after eating.
- Coffee ground emesis if
present means gastrointestinal
hemorrhage (hematemesis)
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A. Gastritis, cont.
exclude: - infections (e.g. helicobacter pylori)
- alcohol intake,
- spicy diet,
- other drugs e.g. NSAIDs
- other diseases e.g. bile reflux, HIV,
Auto-immune diseases, renal or
liver impairment
Investigations: stool analysis for occult blood,
maybe gastroscopy needed
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Algorithmic management of Gastritis
- Hematemesis +
Emergency refer to hospital
No Hematemesis, only epigastric pain, burning sensation …etc.
Give drugs with or after food, avoid coffee, alcohol, smoking
If no improvement, give H2 blocker or proton pump inhibitor
If no improvement, give antacid e.g. Mg Hydroxide.
Away from Fluoroquinolone at least 3 hours
If no improvement , If receiving ethionamide, PAS,
clofazimine consider reduction dose. Consider treatment for
Helicobacter pylori and GIT consultation
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B. Diarrhea:
Diarrhea is frequent (3-4) &/or watery bowel
movements
• exclude: - infections (giardia, amoebic or
bacillary dysentery, or other infectious causes)
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Algorithmic management of Diarrhea:
stools frequent &watery
No blood,
mucous, fever
•
•
•
•
stools frequent & loose
With blood,
mucous, fever
Infection rolled out
Rehydrate
Check electrolytes
Anti-diarrheal e.g.
Loperamide (2 mg orally
after each episode of up to
10 mg total / day
Encourage fluid intake,
check serum electrolytes
•
•
•
•
Role out infection
Treat accordingly
Avoid anti-diarrheal
Check electrolytes
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C. Nausea and vomiting
Algorithmic management
No hematemesis
Dehydrated
If not and hepatitis
rolled out
•
•
•
•
Hematemesis
Urgent referral to hospital
• Check electrolyte
• Rehydrate IV
• Hospitalization to correct fluid
electrolyte disturbance
Administer oral anti-emetics
Use benzodiazepines in anxiety (avoided in Co2 retention)
Administer IM/IV anti-emetics if no improvement.
Consider reducing the dose or suspending it for a short time
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D. Hepatitis:
• Nausea, vomiting, jaundice, scleral icterus, teacolored urine, pale stool, and diminished appetite
• Serum transaminases &/or Serum bilirubin exceed
three times normal level.
Causes include:
• Infections (e.g., viral A B C, amoebic, TB etc.),
• Autoimmune disease,
• Alcoholism,
• Medications, including anti-tuberculosis drugs, antiepileptics, acetaminophen, sulfa drugs, erythromycin
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I) Management of Gastro-intestinal intolerance
(SGOT) ALT (SGPT), direct or bilirubin >3 times
normal values
Stop all drugs
Role out other
causes
TREATMENT of HEPATITIS
 Hospitalization for severely ill patient
 Symptomatic treatment as needed or the underlying cause if appropriate
 Wait for normalization of serum liver tests prior to considering re-initiation of
Anti-tuberculosis medications
 If possible, eliminate the most likely agent from the regimen
 Reinitiate anti-tuberculosis medications, one by one, with serial monitoring
of serum liver tests
 Introduce agents most likely to cause hepatitis first
 If possible, replace the hepatotoxic medications with equally efficacious antituberculosis medications without compromising the regimen.
 Follow up serum liver test every month throughout treatment.
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II) Allergic and dermatological adverse reactions
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Allergic and dermatological adverse reactions
Minor
• Skin pigmentation
• Photosensitivity
• Dry skin
Moderate to severe adverse
reactions
• Hypersensitivity
• Rash
• Purpura
• Allergic dermatitis
• Exfoliative dermatitis,
Steven Johnson Syndrome
• Photosensitivity
• Anaphylaxis /Angiodema
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A. Anaphylaxis
Fatal and appears within minutes of the administration of the
offending medication.
• Symptoms include:
• Signs include:
– Difficulty of breathing (often
with wheezing),
– Pruritis,
 Hoarseness, sensation of a
“lump” in the throat,
– Urticaria (with or without
angioedema),
– Nausea, Vomiting,
– Cramps,
– Diarrhea




stridor, wheezing, swelling
of the tongue, hoarseness
Systolic blood pressure
<90mm Hg (shock)
– Sometimes, patient also presents
with fever, arthralgia, myalgia
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Management
EMERGENCY
 Evaluate for airway obstruction, exclude foreign
body aspiration,
 Administer epinephrine 0.2- 0.5 ml 1:1000 SC
 Re-administer epinephrine if the symptoms persist
after 20 min
 Administer antihistamine and corticosteroids
 Intravenous fluids to expand intravascular volume
 Oxygen
 Consider intubation if necessary
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B. Steven Johnson syndrome
• Starts as non-specific upper respiratory tract infection.
– This usually is part of a 1- to 14-day prodrome during which fever, sore
throat, chills, headache, malaise may be present.
– Vomiting and diarrhea are occasionally noted as part of the prodrome.
• Muco-cutaneous lesions develop abruptly and typically nonpruritic.
• symptoms are as follows:
–
–
–
–
–
Cough productive of a thick purulent sputum
Headache
Malaise
Arthralgia
Fever, reported in 85% of cases.
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Signs include:
– Fever
– Orthostasis
– Tachycardia
– Hypotension
– Altered level of
consciousness
– Epistaxis
– Conjunctivitis
– Corneal ulcerations
– Vulvovaginitis or
balanitis
– Seizures, coma
Symptoms include:
– Cough productive of a
thick purulent sputum
– Headache
– Malaise
– Arthralgia
– Fever, reported in 85%
of cases.
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Management
EMERGENCY
• Stop all drugs
• Administer aggressive hydration
• Administer antihistamine and/or
corticosteroids
• Refer to hospital
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Other allergic skin reactions
Patients may have:
Skin rash, itching, dry skin, photosensitivity
Management:
• Consider allergic reaction
• Administer antihistamine and/or corticosteroids
• PRN for symptoms
• Rule out other non-allergic causes e.g. scabies,
insect bites ..etc.
• If associated with sun exposure, use sunscreens
or avoid exposure
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In all allergic and dermatological reactions:
In addition to the specific management:
• Determine the offending substance (food, medication,
insect bites)
• If an anti-tuberculosis medication is highly suspected and
the reaction was life-threatening, discontinue medication
and replace with equally efficacious anti-tuberculosis drug.
• When any of the severe allergic reactions are present, all
anti-tuberculosis medications should be suspended.
• Desensitization should not be performed in patients with
a history of Stevens-Johnson syndrome.
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Desensitization,
General considerations
• It is essential to determine which drug
caused the reaction.
• Once the patient has improved, antituberculosis therapy can be restarted as a
“challenge”– a partial dose – in a serial
fashion
Desensitization,
General considerations
• Start the most likely allergen administered first.
• Desensitization is only done when other therapeutic
options are extremely limited.
• Challenges is done to medicines in which reactions
were mild to moderate.
• Rarely agent that has caused anaphylaxis can only
be introduced through a desensitization protocol
under careful, hospital based observation.
Example of desensitization protocols
III. Neurological and Psychiatric adverse reactions
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Common mild adverse
reactions
• Dizziness
• Headache
• Fatigue
• Somnolence
• Insomnia
• Confusion
• Irritability
• Anxiety
• Behavior changes
Moderate to severe
adverse reaction
• Seizure
• Syncope
• Peripheral neuropathy
• VIII nerve damage:
hearing loss, vestibular
impairment
• Psychosis
• Suicidal ideation
• Depression
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Management of Headaches
Rule out meningitis:
• Neck rigidity, photophobia,
• fever,
• confusion,
• somnolence
Rule out migraines:
• Prior to treatment similar headaches
• pulsating, with nausea, vomiting, vision
changes?
• Discrete episodes
• lasting hours,
• relieved by darkness, sleep
If positive, refer to
hospital
•
•
•
•
analgesics,
low-dose beta-blockers,
sumatriptan,
Supportive measures
TREATMENT
• analgesics (e.g., acetaminophen, ibuprofen, etc.)
• Avoid non-steroidal anti-inflammatory agents in patients with hemoptysis or gastritis
• Psychosocial support
• Encourage adequate fluid intake
• Confirm patient on proper dose of pyridoxine
• If no response, Amitriptyline 50-150 mg at night & consider lowering Cycloserine dosage
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Management of Seizures
Presentations
• Recurrent movement of a part of the body (e.g., finger, hand,
face, etc.) with or without loss of consciousness?
• Loss of consciousness followed by rhythmic contraction of
muscles? Tongue biting? Urinary or fecal incontinence?
• Headache, confusion, drowsiness, or amnesia immediately
after the event?
• Sensory disturbances (numbness, dizziness, auditory or visual
hallucinations, sensations of fear or anger, etc.)?
• Psychotic changes (psychosis, hallucinations, sensations of fear
or anger, etc.)
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Management of Seizures , cont.
• Rule out other causes e.g. meningitis, encephalitis, alcohol
withdrawal, hypoglycemia, hyper- or hyponatremia, hyper- or
hypocalcaemia, cerebrovascular accident, or space-occupying
lesion.
• Consider neurology consultation
• Initiate anti-convulsant therapy (e.g. phenytoin 3-5 mg/kg/d)
• Increase pyridoxine to 300mg daily
• Lower dose or discontinue suspected agent, if this can be
done without compromising regimen
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Management of Seizures , cont.
General considerations:
• Anti-convulsant is generally continued until MDR-TB
treatment completed or suspected agent discontinued.
• History of prior seizure disorder is not a contraindication to
the use of agents listed here if patient’s seizures are well
controlled and/or patient is receiving anti-convulsant therapy.
• Patients with history of prior seizures may be at increased risk
for development of seizures during MDR-TB therapy.
• Seizures not a permanent squeal of MDRTB treatment
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Management of Peripheral neuropathy
Symptoms:
• Burning sensation,
• Numbness of both feet, worse at night or when
walking
• Leg weakness when walking
• Leg pain
Rule out other causes, including:
diabetes, alcoholism, vitamin deficiencies, HIV,
hypothyroidism, uremia etc.
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Management of Peripheral neuropathy, cont.
Treatment
• Initiate low-dose tricyclic antidepressant (e.g.,
amitriptyline 25-75 mg at bed time)
• Confirm patient is on proper dose of pyrodoxine.
If no improvement
• Decrease dose of responsible medication (e.g.,
Ethio. to 750 mg, CS to 750 mg, aminoglycoside
to 750 mg, or use CM instead etc.), then resume
normal dose once pain is controlled
• Consider acetaminophen and/or NSAIDs for pain
relief
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Management of VIII cranial nerve toxicity
• Ototoxicity–Hearing loss is confirmed by audiometry.
• Patients with previous exposure to aminoglycosides may have baseline
hearing loss.
• Hearing loss generally is not reversible.
• The aim is to Keep patient quality of life to be able to hear people voice
• Change parenteral to CM if patient susceptibility has documented.
• Lower dose of suspected agent, (consider administration three times a
week).
• Discontinues suspected agent if this does not compromise the regimen.
• Patients with renal failure has increased risk
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Management of depression
Symptoms of major depressive disorder can include:
 changes in sleep pattern,
 loss of interest in usual activities,
 feelings of guilt,
 diminished energy,
 decreased concentration,
 lack of appetite,
 psychomotor retardation (slowed movement and
thought),
 suicidal ideation.
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Management of depression, cont.
EVALUATION
More than two weeks of persistent sadness,
loss of interest, loss of appetite,
weight change, insomnia, fatigue, lack
of concentration, feelings of worthlessness
or guilt.
• Rule out psychosis Delusions, hallucinations,
incoherent thoughts or speech, inappropriate or
catatonic behavior
• Rule out hypothyroidism.
Suicidal or
homicidal
ideation?
EMERGENCY
• Consider hospitalization
• Monitor closely to
ensure safety
TREATMENT
• Consider psychiatric consultation
• Initiate antidepressant therapy
• Provide intensive psychological therapy with counseling to patient and family
• Provide emotional support from the family and treatment supporter aimed at
resolution of causes of stress
• Organize group therapy or informal support groups
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Management of Psychosis
Disintegration of personality or loss of contact with reality
EVALUATION
Patient sees or hears things that others do not
perceive? Unintelligible thoughts or speech?
Bizarre behavior?
TREATMENT
• discontinue Cycloserine or replace suspected
agent with equally efficacious anti-tuberculosis
drug
• Consider psychiatric consultation & initiate antipsychotic medications
• Evaluate psychosocial stressors
• Confirm patient is on proper dose of pyrodoxine.
• Anti-psychotic medication can be continued to
the end of treatment if recurrence occur.
• Cycloserine can be re-initiated in a lower dose
after remission.
Suicidal or homicidal
ideation?
EMERGENCY
• Consider hospitalization
• Monitor closely to
ensure safety
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IV. Management of fluid and
electrolyte disturbances
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Management of Hypokalemia
Potassium level <3.5 meq/L).
Causes:
• Some of the anti-tuberculosis medications–-in particular the
aminoglycosides and Capreomycin—cause renal wasting of potassium
and magnesium.
• Severe vomiting or diarrhea
TREATMENT
• Replete potassium orally or IV
• Treat associated conditions such as vomiting or diarrhea.
• Monitor potassium closely to determine when repletion may be
discontinued
• Empiric magnesium repletion or check Mg level and replete as needed
• Discontinue any arrhythmogenic medications (e.g., digoxin,
amytriptyline,)
• Consider checking calcium and replete as needed.
If severe consider stopping the injectable drug.
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Management of Hypokalemia, cont.
Recommended repletion protocol
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V. Endocrine adverse reactions
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V. Endocrine adverse reactions
Common mild adverse
reactions
• Poor glycemic control in
diabetics
• Changes in menstrual cycle
• Gynecomastia
• Impotence
Moderate to severe
adverse reactions
• Hypothyroidism
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Management of Hypothyroidism
EVALUATION
Fatigue, enlarged thyroid, lack of energy, weakness, depression,
constipation, cold intolerance, lack of concentration, loss of
appetite, weight gain, dry skin, coarse hair, hair loss.
Rule out depression and
check TSH, Free T4 & T3
TSH >10 mIU/L
TREATMENT
• Administer levo-thyroxine
- Adult patients under 60 years without evidence of heart disease may be started
on 50-100 mcg daily
- Therapeutic dosage often between 100-200 mcg daily
- Repeat TSH every month and adjust the dose of thyroxine; adjustment is made
in 12.5-25 mcg increments till adjusted then TSH every 3-4 months.
- Continue thyroxine and TSH estimation 2-3 months after treatment completion.
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Thank You
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