Presentation on theme: "COMPLICATIONS OF TB TREATMENT AND THEIR MANAGEMENT"— Presentation transcript:
1 COMPLICATIONS OF TB TREATMENT AND THEIR MANAGEMENT Dr Liza Ahmad Fisal14 July 2010
2 Complications Adverse drug reaction Aggravate pre-existing conditions Renal impairmentLiver impairmentPeripheral neuropathyInteract with existing drugs
3 Adverse drug reactionMay seem mild and harmless but may herald serious complications:Nausea & vomiting – hepatitisWeakness / off legs - vestibulotoxicityRash - Stevens Johnson syndromeIdentifying the culprit can be difficult because of the overlapping adverse effects.
8 Rifampicin drug interactions Microsomal enzyme inducer → ↓ plasma concentration of certain drugs → ↓ drug efficacy.Examples:Combined-oral contraceptivesWarfarinCorticosteroidsPhenytoinSulphonylurea hypoglycaemicsStatinsTheophyllineMethadoneT4
9 Rifampicin & COC Less efficacious → unwanted pregnancy Higher dose of oestrogen (50mcg) or alternative methodsThroughout treatment with rifampicin and at least 1 month after rifampicin completed
16 Managing anti-TB side effects Confirm diagnosis.Determine whether side effect is minor/major.Managing minor/major side effects accordingly.
17 Principles of management Minor adverse effectsContinue TB treatmentGive symptomatic treatment.Close monitoringMajor side-effects,Stop the drug responsible or TB treatment (if drug responsible unknown)Refer
26 Drug-induced liver injury (DILI) Rare but potentially fatal adverse effectHepatotoxicity ALT > 3 x ULNALP > 2 X ULNCulprits - Isoniazid, Rifampicin, PyrazinamideCombining hepatotoxic drugs increases toxicity
27 V. J. Navarro and J. R. Senior Drug-Related HepatotoxicityN. Engl. J. Med., February 16, 2006; 354(7):
28 Natural history DILI Drug-induced acute liver failure: Significant morbidityHigh mortality - 20% survival in the absence of liver transplantationThe clinical course after withdrawal of the drug is variable:Better after discontinuationWorsen for weeks before improvement is seenResolution of cholestatic injury take longer compared to the hepatitis form (?cholangiocytes regenerate more slowly)
29 Natural history of DILI Patients rarely develop chronic liver disease after an acute severe DILI.Patients with cholestatic/mixed liver disease were more prone to developing chronic injury (9%), than those with the hepatocellular form (4%)Prolonged DILI was mostly seen in patients with cholestatic/mixed types of hepatotoxicity.
30 What to do? Stop: Screen: ALT > 3 x ULN with symptoms* ALT > 5 x ULN without symptomsScreen:Hepatitis A, B, CUSS HBSOther hepatotoxics – other drugs, TCM, alcohol
31 WHO management of drug-induced hepatitis Re-introduce anti-TB when:LFTs normalisedAsymptomaticBridge if persistent abnormal LFTs or serious TB:SEO
32 Re-introducing anti-TB One at a timeIn this order: Rifampicin → Isoniazid → PyrazinamideMonitor LFTsIf symptoms recur or LFTs become abnormal as the drugs are reintroduced, the last drug added should be stoppedIf OK on Rifampicin & Isoniazid and hepatitis was severe, omit challenging with Pyrazinamide
33 If rechallenge unsuccessful, give alternative regime: 2 hepatotoxics2HRE/7HR2SHRE/6HR6-9REZ1 hepatotoxic2SHE/10HE0 hepatotoxic18-24 SEO
35 Rechallenging* Rechalleging with anti-TB drug is done when the drug responsible is unknown.Identifying culprit drug necessary to continue TB treatmentGirling protocol and its modified version is used
36 Contraindications to drug rechallenge Rifampicin-induced thrombocytopenia, hemolytic anemia, acute renal failure, shockIsoniazid-induced lupusEthambutol-induced optic neuropathyPyrazinamide-induced acute gouty arthritisStreptomycin-induced vestibuloneuropathy
38 Changing regimen EHRZ (Dose 1-14) SEO (Dose 15-21) H introduced once LFT normalisedR introduced when patient tolerate H, usually day 4 of rechallenge.DoseRegimenNotes1-14EHRZ1st regimen15-21SEOBridging regimen22SEO + H1D1 rechallenge with H23SE0 + H2D2 rechallenge with H24SEO + H3D3 rechallenge with H25SHEO + R1D1 rechallenge with R26SHEO + R2D2 rechallenge with R27SHEO + R3D3 rechallenge with R28SHERONew regimen
40 ReferenceDiagnosis, management and prevention of drug-induced liver injury S Verma, N Kaplowitz Gut 2009;58:ATS Hepatotoxicity of Antituberculosis Therapy Subcommittee An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy Am. J. Respir. Crit. Care Med. 2006; 174:WHO 2009 Treatment of tuberculosis: guidelines - 4th ed