management of adverse effects of anti-tb drugs (part i) dr. ashraf abdulhaseeb chest diseases...
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Management of Adverse Effects of Anti-TB drugs (part I)
Dr. Ashraf AbdulhaseebChest Diseases Consultant
Chief of DR-TB center, Abbassia Chest Hospital
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Presentation outline:• Monitoring adverse effects• Main adverse effects and suspected drugs.• General considerations of adverse effects
management.• Commonly used ancillary drugs.
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Monitoring of adverse effects:
Aims at:• Early detect and treat adverse effects
• Prevent /minimize toxic effects or organ damage
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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.
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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.
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Initial pretreatment monitoring includes:1. Thorough medical history and physical examination. 2. History of concomitant conditions which can
contribute occurrence of drug intolerance3. History of adverse drug reactions.4. History of allergic reactions5. Complete blood count6. Liver functions:
Total serum BilirubinSGPT & SGOTTotal serum albumin, total serum protein and A/G ratio.
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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.
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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
Monthly
CBC Monthly
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II) Lab investigation schedule during treatment to monitor adverse effects, cont.
Hemoglobin and WBC If on linezolid, monitor weekly at first, then monthly
Lipase 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
Serum glucose If receiving gatifloxacin, monitor glucose frequently (weekly) and educate patient on signs and symptoms of hypoglycaemia and hyperglcycaemia
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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.
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Special attention should be paid for:
Liver toxicity. Vestibular and hearing toxicity with injectable
drugs. Psychiatric disorders with Cycloserine. Allergic reactions. Hematological changes.
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Recording the adverse effects in patient file:
Description of the
adverse reaction
Date Severity*
ChangeOf
treatmentif made
Datetreatmentchange
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:_______________________________________________________________
Patient name__________________________________ Patient ID____________________TB registrations number ___________________________________________________
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Side effects
Gastriti
s
Peripheral
neuritis
Diarrh
ea
Hypoth
yroidism
Vomiting
Depression
Electrolyt
e disturb
ance
Nause
a
Arthriti
s
Psychosis
Allergy
Skin ra
sh
Sleep dist
urban
ce
Headac
he
Hearing d
efect
Dizziness
Convulsi
ons
consti
pation
Gynae
comasti
a
Hepatitis
Optic neuriti
s
Renal fai
lure0%
10%
20%
30%
40%
50%
60%
70%
80%73%
57%53%
46%
32%
25%23% 22% 20%
13% 13% 13% 12%8% 7% 6% 6% 5% 5% 4%
2%
Per
cent
of
pati
ent
Adverse effects in cohort 127 patients, Egypt 2009
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Common adverse effects and suspected drugs
Adverse effects Suspected drugsSeizures 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,
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Adverse effects Suspected drugs
Gastritis PAS, Prothionamide/Ethionamide, PyrazinamidHepatitis 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
Common adverse effects and suspected drugs, cont.
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Classification of Adverse Effects
Allergic and dermatological:Mild Moderate to severeSkin pigmentationsPhoto-sensitivityDry skin
HypersensitivityFeverRashPurpuraAllergic dermatitisExfoliative dermatitisAnaphylaxis /Angiodema
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Classification of Adverse Effects
Gastrointestinal:Mild Moderate to severeNausea/VomitingAnorexiaMetallic taste/salivationStomatitis /GlossitisDiarrhea BloatingAbdominal cramps
GastritisGastric ulcerHepatitis
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Classification of Adverse EffectsNeurological and Psychiatric:Mild Moderate to severeDizzinessHeadacheFatigueSomnolenceInsomniaIrritabilityAnxiety
SeizurePeripheral neuropathyVIII nerve damage: hearing loss, vestibular impairmentPsychosisSuicidal tendencyDepressionConfusionBehavior changes
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Classification of Adverse EffectsFluid and electrolyte disturbance &others:
Mild Moderate to severeMyalgiaCrampsArthralgiaCandidiasis, stomatitis
Electrolyte disturbancesDehydrationRenal failureOptic neuritisAnemia
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Classification of Adverse EffectsEndocrine adverse effects:
Mild Moderate to severeChanges in menstrual cycleGynecomastia Impotence
Uncontrolled diabetesHypothyroidism
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Management of adverse effectsGeneral 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
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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.
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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
General considerations, cont.
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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.
General considerations, cont.
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- 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.
General considerations, cont.
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Commonly used ancillary medications
Nausea, vomiting, upset stomach
Metoclopramide, prochlorperazine, 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 (non-AIDS patient) Fluconazole, clotrimazole lozenges ..etc
Diarrhoea Loperamide or other anti-diarrheal
Depression Selective serotonin reuptake inhibitors (fluoxetine, sertraline), tricyclic antidepressants (amitriptyline)
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Prophylaxis of neurological complications of cycloserine
Pyridoxine (vitamin B6)
Peripheral neuropathy Amitriptyline
vestibular symptoms Meclizine, dimenhydrinate, prochlorperazine, promethazine
Musculoskeletal pain, arthralgia, headaches Ibuprofen, paracetamol
Cutaneous reactions, itching
Hydrocortisone cream, calamine, caladryl lotions
Systemic hypersensitivity reactions
Antihistamines (diphenhydramine, chlorpheniramine, dimenhydrinate), corticosteroids (prednisone, dexamethasone)
Commonly used ancillary medications
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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
Commonly used ancillary medications
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Severe anxiety Lorazepam, diazepam, clonazepam
Insomnia Dimenhydrinate
Psychosis Haloperidol, thorazine, risperidone (consider benzotropine or biperiden to prevent extrapyramidal effects)
Seizures Phenytoin, carbamazepine, phenobarbital
Commonly used ancillary medications
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Thank you