drug induced he pa to toxicity

8/3/2019 Drug Induced He Pa to Toxicity

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Dr. Waqar Munir


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42 years old Filipino lady, working as ahousemaid for 3 years, underwent pre-employment checkup during change of

sponsorship in April 2011 and was found to havebilateral apical infiltrates on chest radiograph.She admitted at that time to having mild on andoff cough but no fever or night sweats.

Sputum smear & culture (2 sets) was donewhich was negative at 6 weeks. A Quantiferontest was positive in April 2011 and patient wasdiagnosed as ?latent tuberculosis infection.


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She received Isoniazid 600mg twice per weekand Rimactazid (INH + Rifampin) 600/300 twiceper week (INH 1800 mg / wk & Rifampin 600 mg

/ wk) since 2nd June 2011 for 6 months and wasdue to finish her course of anti tuberculousagents on 2nd December 2011 as DOTS.

Patient started to feel nauseated and fatigued atthe end of October. LFTs were normal and shewas reassured at TB Clinic, however shecontinued to have symptoms.


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She was referred to A&E on 23/11/2011 with fourdays history of severe nausea, loss of appetite,fatigue and one episode of vomiting containing

blood. No bleeding from any other site.

She also complained of mild right sidedabdominal pain and noticed yellowishdiscolouration of her sclera and tea coloured

urine.

Patient is non-Alcohol consumer and non-smoker and no history of blood transfusion or

extramarital relations or IV drug abuse.


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T) 36.5 oC B/P) 97/64 H/R) 68/min R/R) 18/minSpO2) 99% RA Ht) 157cm Wt)54.4kg

Generally, she was conscious and oriented to time, place

and person. She had yellowish discoloration of sclera andskin. No lymph node enlargement and JVP was not raised.

Chest, CVS & CNS : No abnormality detected.

Abdomen: soft, lax, non distended with mild tendernessat right hypochondrium and epigastrium. Liver waspalpable 2 finger breadth below right costal margin withfirm rounded edge and mild tenderness. Liver span 14cm.No ascities.


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CBC:W: 4.7 Hb: 12.8 MCV: 82 PLT: 178

S/E:

BUN: 1.8 Cr: 48 Na: 141 K:5.2HCO3: 26

LFT:ALT: 926 AST: 847 ALP: 165 T.Bilirubin: 192

Direct: 162 Alb:34

Coag:PT: 13 APTT: 38 INR: 1.3


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USG Abdomen: mild coarse liver.

Autoimmune workup: negative

ANA: 1:160 IgG: 2640

Hep. A B C & E Serology: negative

Adenovirus, EBV, CMV: negative

USG Doppler of Liver/ Portal system: Normal


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Patient was admitted to medical unit as case ofdrug-induced hepatitis. Anti-TB medicationswere stopped 2 days before coming to the

hospital as patient had already completed 5.5months of therapy.

LFTs and Coagulation profile was followed dailywhich showed a rise.


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However the patient started to improve clinicallyand her symptoms resolved. She was followedup closely by GI team.

Gradually her LFTs and Coagulation Profilestarted to decline and patient was discharged on08/11/2011 with followup after 1 week of herLFTs in the clinic.


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Funded by the Centers for Disease Control and Prevention

The New England Journal ofMedicine, Vol 365, Dec 8, 2011

Timothy R. Sterling, M.D., M. Elsa Villarino, M.D., M.P.H., Andrey S.

Borisov, M.D., M.P.H., Nong Shang, Ph.D., Fred Gordin, M.D., Erin Bliven-Sizemore, M.P.H., Judith Hackman, R.N., Carol Dukes Hamilton, M.D., Dick

Menzies, M.D., Amy Kerrigan, R.N., M.S.N., Stephen E. Weis, D.O., MarcWeiner, M.D., Diane Wing, R.N., Marcus B. Conde, M.D., Lorna Bozeman,M.S., C. Robert Horsburgh, Jr., M.D., Richard E. Chaisson, M.D., for the TB

Trials Consortium PREVENT TB Study Team*


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Treatment of latent Mycobacteriumtuberculosis infection is an essential

component of tuberculosis control andelimination. The current standard regimen ofisoniazid for 9 months is efficacious but islimited by toxicity and low rates of treatmentcompletion.


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open-label, randomized noninferiority trial

compared 3 months of directly observedonce-weekly therapy with rifapentine (900mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg)(isoniazid-only group)


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subjects at high risk for tuberculosis enrolledfrom United States, Canada, Brazil, and

Spain.

followup for 33 months.

The primary end point was confirmedtuberculosis, and the noninferiority marginwas 0.75%.


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Tuberculosis developed in 7 of 3986 subjectsin the combination-therapy group(cumulative rate, 0.19%) and in 15 of 3745subjects in the isoniazid-only group(cumulative rate, 0.43%), for a difference of0.24 percentage points.

Rates of treatment completion were 82.1% inthe combination-therapy group and 69.0% inthe isoniazid-only group (P


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Rates of permanent drug discontinuationowing to an adverse event were 4.9% in the

combination-therapy group and 3.7% in theisoniazid-only group (P = 0.009).

Rates of investigator-assessed drug-relatedhepatotoxicity were 0.4% and 2.7%,respectively (P


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The use of rifapentine plus isoniazid for 3months was as effective as 9 months of

isoniazid alone in preventing tuberculosis andhad a higher treatment-completion rate.

Long-term safety monitoring will beimportant.

drug induced he pa to toxicity

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