Management of Adverse Effects of Anti-TB drugs (part I) Dr. Ashraf Abdulhaseeb Chest Diseases Consultant Chief of DR-TB center, Abbassia Chest Hospital.

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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