adverse effects of ATT.pptx

management of adverse effects of antitubercular drugs

1. Management of adverse effects of ATT & ATT in special situations Dr G.VENKATA RAMANA MBBS DNB FAMILY MEDICINE

2. FIRST LINE ANTI-TB DRUGS Isoniazid H Rifampicin R Pyrazinamide Z Ethambutol E

3. GROUPS OF SECOND LINE ANTI-TB DRUGS GROUP NAME OF DRUG GROUP A Levofloxacin or Moxifloxacin Bedaquiline Linezolid Lfx Mfx Bdq Lzd GROUP B Clofazimine Cycloserine or Terizidone Cfz Cs Trd GROUP C Ethambutol Delamanid Pyrazinamide Imipenem-cilastatin or Meropenem Amikacin (or) Streptomycin Ethionamide or Prothionamide p- aminosalicylic acid E Dlm Z Ipm-Cln Mpm Am S Eto Pto PAS

4. Adverse drug effects of first-line anti-TB drugs Drug Main Effects Rare Effects Isoniazid Peripheral neuropathy Skin rash Hepatitis Sleepiness and lethargy Convulsion Psychosis Arthralgia Anaemia Rifampicin Gastro-intestinal: Abdominal pain nausea, vomiting Hepatitis General cutaneous reactions Thrombocytopenic purpura Osteomalacia Pseudomembranous colitis Pseudo-duodenal crisis Acute renal failure Haemolytic anaemia Pyrazinamide Arthralgia Hepatitis Gastrointestinal problems Cutaneous reactions Sideroblastic anaemia Ethambutol Retrobulbar neuritis Generalized cutaneous reactions Arthralgia Peripheral neuropathy Hepatitis (very rare)

5. Name of drug Main side effect Levofloxacin ( Lfx ) Seizures, headache Moxifloxacin ( Mfx ) Q- Tc prolongation with moxifloxacin , especially high dose Bedaquiline ( Bdq ) Gastritis, hepatotoxicity, Q- Tc prolongation, dyselectrolytemia , myopathy Linezolid ( Lzd ) Peripheral neuropathy, optic neuritis, bone marrow depression Clofazimine ( Cfz ) Reddish discoloration of skin, Q- Tc prolongation, phototoxicity Cycloserine (Cs) Psychosis, depression, insomnia Terizidone ( Trz ) Headache, tremors, insomnia, depression, convulsions, altered behaviour and suicidal tendencies

6. Name of drug Main side effect Delamanid ( Dlm ) Q- Tc prolongation Imipenem + Cilastatin ( Ipm-Cln ) Diarrhoea , nausea, vomiting Meropenem ( Mpm ) Fever, chills, light-headedness, dizziness, sweating, rapid shallow breathing, skin rash Amikacin (Am) Nephrotoxicity, ototoxicity Streptomycin (S) Nephrotoxicity, ototoxicity Ethionamide ( Eto ) Gastritis, hypothyroidism Prothionamide ( Pto ) Gastritis, hypothyroidism P- aminosalicylic Acid (PAS) Gastritis, hypothyroidism

7. CASE SCENARIO 1 40 year old female came with c/o fever,abominal distension,abdominal pain and weight loss for 2 weeks. on evaluation USG showed ascites with omental thickening.Diagnostic ascitic tap was suggestive of tubercular etiology. Diagnosis: ABDOMINAL TUBERCULOSIS She was started on ATT after pretreatment evaluation After starting ATT patient developed vomiting,epigastric discomfort What is your diagnosis and how will u manage this patient?

8. Do LFT,RFT If LFT normal,Probable diagnosis- ATT induced gastritis Reassure patient. Give drugs with less water and over a longer period of time(e.g. 20 minutes) Donot give drugs on an empty stomach Maintain hydration Consider treatment with anti-emetics ( e.g.domperidone ) and proton pump inhibitors ( e.g.Omeprazole )

9. CASE SCENARIO 2 25 year old female came with c/o fever,cough for 2 weeks,weight loss,hemoptysis.chest xray suggestive of PTB.sputum positive for AFB and there is no drug resistance . Diagnosis-pulmonary TB Patient was started on ATT (HRZE) after pretreatment evaluation. After few days patient developed jaundice,anorexia , vomiting.lab investigations showed deranged LFT with elevated bilirubin (>2ULN) and liver enzymes ( AST/ALT>3ULN) . What is your diagnosis? How will you manage this patient ?

10. ATT ASSOCAITED HEPATOTOXICITY Stop all hepatotoxic drugs Need urgent ATT : Change to non-hepatotoxic drugs ( Fluroquinolones , ethambutol & aminoglycosides) No need for urgent ATT : R epeat LFT after a week & reintroduce only if ALT and AST < 2 ULN & normal bilirubin Start one drug at time: helps identify the culprit Rifampicin may be introduced at 10 mg/kg dose After one week add Isoniazid 5 mg/kg if LFT normal After one week add pyrazinamide 25 mg/kg if LFT is normal Duration of ATT: count only when full ATT is started

11. ATT ASSOCAITED HEPATOTOXICITY IF R and H tolerated Donot restart Z Prolong treatment with R,H and E for 9 months If R is implicated in hepatitis Give SHE for 2 months f/b HE for 10 months If H is implicated in hepatitis Give REZ for 9months

12. CASE SCENARIO 3 23 year old male came with c/o fever,cough , shortness of breath.His X ray showed right sided pleural effusion,diagnostic pleural tap was suggestive of tubercular effusion started on ATT after pretreatment evaluation. A few days later patient came with c/o decreased vision and not able to identify red,green colors. How will you evaluate and manage this patient?

13. Probable diagnosis: Ethambutol induced optic neuritis Stop Ethambutol Refer to O pthalmologist to rule out other cause Impaired vision may, within a few weeks, or may not return to normal after stopping E thambutol . Don’t restart ethambutol .

14. CASE SCENARIO 4 40 year old female came with c/o fever,cough for 2 weeks and weight loss.on evaluation CXR suggestive of PTB.Sputum for microscopy AFB negative.CBNAAT -negative. Diagnosed as Clinically diagnosed PTB Patient was started on ATT after pretreatment evaluation. A fter few days patient came with complaints of joint pains. How will u evaluate and manage this patient?

15. Probable diagnosis- Arthralgia secondary to pyrazinamide >> ethambutol >isoniazid Encourage patients to increase intake of liquids Give NSAIDs like paracetamol,Aspirin or ibuprofen and in severe cases Indomethacin for a week to 10 days In severe cases estimate serum uric acid levels If uric acid levels are significantly raised treat with NSAIDs and colchicine. Allopurinol is not effective In severe cases with normal or slightly elevated uric acid consider reduction of the dose of Pyrazinamide

16. CASE SCENARIO 5 30 year old male with no comorbidities came with c/o fever,swelling in the neck for 2 weeks,weight loss. FNAC was done suggestive of tubercular lymphadenitis. Patient was started on ATT after pretreatment evaluation. A fter few days patient developed Tingling in the hands and feet. what is ur diagnosis and how will u manage this patient?

17. Probable diagnosis: Isoniazid induced peripheral neuropathy Give pyridoxine100-200mg/day until symptoms subside. Patients not responding to pyridoxine will require treatment with amitryptiline

18. CASE SCENARIO 6 25 year old male came with c/o fever cough,shortness of breath,chest pain.chest xray showed globular heart.2Decho showed massive pericardial effusion. Diagnostic pericardiocentesis suggestive of tubercular etiology. Diagnosis – TB pericarditis Patient was started on ATT after pretreatment evaluation After few days patient developed skin rashes,itching How will u manage this patient ?

19. Itching without rash or a mild rash Continue treatment and give antihistamines Itching with moderate to severe rash Stop all drugs till symptoms subside Treat with antihistamines Patients with mucosal involvement, fever and hypotension will require treatment with corticosteroids When the reaction subsides reintroduce drugs one by one in this order INH,Rifampicin , Pyrazinamide and Ethambutol Re-introduce each drug in a small dose and gradually increase over 3 days before introducing the next drug.

20. CASE SCENARIO 7 30 year old male diagnosed to have pulmonary TB with chronic liver disease was sarted on no hepatotoxic drug regimen SLE. After 1 month patient developed r inging in the ear, l oss of hearing,dizziness and loss of balance How will u evaluate this patient?

21. STOP Streptomycin Refer to ENT specialist for opinion As hearing loss is usually not reversible do not restart Streptomycin