Treatment of Tuberculosis-Treatment of Tuberculosis-Not just another pillNot just another pill

Karen Fitzmaurice, RNKaren Fitzmaurice, RN

Martha Ainslie, MDMartha Ainslie, MD

Alfred Gin, PharmDAlfred Gin, PharmD

Objectives:Objectives:

By attending the session, the attendee will By attending the session, the attendee will be able to:be able to:• Become familiar with the first and second line Become familiar with the first and second line

anti-tuberculosis antibiotics and the standard anti-tuberculosis antibiotics and the standard treatment regimestreatment regimes

• Identify the common adverse effects and drug Identify the common adverse effects and drug interactions associated with these antibioticsinteractions associated with these antibiotics

• Describe problem-solving techniques that are Describe problem-solving techniques that are used to help identify and manage common used to help identify and manage common adverse effectsadverse effects

OutlineOutline

Review the first line agentsReview the first line agents Discuss duration of therapyDiscuss duration of therapy Review common side effects and Review common side effects and

managementmanagement Review treatment of TB in special Review treatment of TB in special

populationspopulations Briefly talk about drug resistance and Briefly talk about drug resistance and

second line agentssecond line agents

The scope of the problemThe scope of the problem A 2 cm cavity contains 10A 2 cm cavity contains 108 8 organismsorganisms

• A patient with active TB will have organisms A patient with active TB will have organisms that are rapidly dividing as well as semi-that are rapidly dividing as well as semi-dormant and dormant organismsdormant and dormant organisms

There are naturally occurring mutations to There are naturally occurring mutations to all our TB drugsall our TB drugs

Use of monotherapy allows the selective Use of monotherapy allows the selective growth of the resistant organisms and growth of the resistant organisms and gives rise to drug resistancegives rise to drug resistance

A prolonged course of antibiotics is A prolonged course of antibiotics is required to kill the semi-dormant and required to kill the semi-dormant and dormant organismsdormant organisms

In order to treat TB you mustIn order to treat TB you must

Take into consideration:Take into consideration:• Known or suspected drug resistanceKnown or suspected drug resistance

Hx of prior TB treatmentHx of prior TB treatment Country of originCountry of origin

• Location of diseaseLocation of disease Standard tx is 6 monthsStandard tx is 6 months TB meningitis: 9-12 monthsTB meningitis: 9-12 months

• Likelihood of adherence and/or adverse Likelihood of adherence and/or adverse reactionsreactions

• Co morbidities and host immune statusCo morbidities and host immune status

Standard treatment regime:Standard treatment regime:

Intensive phaseIntensive phase• Goal is to quickly kill the rapidly dividing Goal is to quickly kill the rapidly dividing

organism to control disease and render organism to control disease and render patient non-infectious and prevent patient non-infectious and prevent emergence of drug resistanceemergence of drug resistance

Continuation phaseContinuation phase• Sterilize the lungs by killing dormant Sterilize the lungs by killing dormant

and semi-dormant organisms to prevent and semi-dormant organisms to prevent relapserelapse

• DOT allows for intermittent therapyDOT allows for intermittent therapy

Give all meds together Give all meds together as a single dose unless:as a single dose unless:

•Profound nausea, vomitingProfound nausea, vomiting

•Swallowing issuesSwallowing issues

Standard treatment Regime:Standard treatment Regime:

Intensive phase (first 8 weeks)Intensive phase (first 8 weeks)• 4 drugs X 8 weeks in the intensive phase 4 drugs X 8 weeks in the intensive phase

INH/RMP/PZA/EMB daily X 14 dosesINH/RMP/PZA/EMB daily X 14 doses• If in hospital – daily until smear negative If in hospital – daily until smear negative

5/7 X 6 weeks (30 doses) WRHA5/7 X 6 weeks (30 doses) WRHA 3/7 X 6 weeks (18 doses) FNIH, unless drug 3/7 X 6 weeks (18 doses) FNIH, unless drug

resistance suspected, then 5/7resistance suspected, then 5/7

• Ethambutol can be dropped if organism Ethambutol can be dropped if organism pansensitivepansensitive

Continuation phaseContinuation phase• Twice weekly INH and rifampin DOTTwice weekly INH and rifampin DOT

2HREZ/4HR2HREZ/4HR22

In intensive phaseIn intensive phase• H,R: kill rapidly dividing TBH,R: kill rapidly dividing TB• Z: works to kill semi dormant TB in the acidic Z: works to kill semi dormant TB in the acidic

environment of the cavity or in macrophagesenvironment of the cavity or in macrophages• E: used to prevent the emergence of RIF E: used to prevent the emergence of RIF

resistance when primary resistance to INH may resistance when primary resistance to INH may be presentbe present

In continuation phaseIn continuation phase• H,R: kill any remaining rapidly dividing cells as H,R: kill any remaining rapidly dividing cells as

well as sterilizing fibrotic areaswell as sterilizing fibrotic areas

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RifampinRifampin

Inhibits RNA polymeraseInhibits RNA polymerase

The most important drug we useThe most important drug we use

Bactericidal against rapidly dividing Bactericidal against rapidly dividing agents, and penetrates into fibrotic areas agents, and penetrates into fibrotic areas to kill semidormant organismsto kill semidormant organisms

• Without rifampin treatment course is 12-18 Without rifampin treatment course is 12-18 monthsmonths

Usual dose 10 mg/kg max 600mgUsual dose 10 mg/kg max 600mg

Rifampin side effectsRifampin side effects Change in colour of urine, sweatChange in colour of urine, sweat Puritis with or without rash: 6%Puritis with or without rash: 6% Hepatotoxicity Hepatotoxicity

• Significant transaminase elevation: rareSignificant transaminase elevation: rare• Can be seen as part of hypersensitivity rxCan be seen as part of hypersensitivity rx

Dose dependent interference with bilirubin Dose dependent interference with bilirubin uptake causing unconjugated uptake causing unconjugated hyperbilirubinemia or jaundice without LFT hyperbilirubinemia or jaundice without LFT abnormalitiesabnormalities

ThrombocytopeniaThrombocytopenia Hypersensitivity rx in 0.07-0.3%Hypersensitivity rx in 0.07-0.3%

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Rifampin Drug InteractionsRifampin Drug Interactions

Potent inducer of cytochrome P450 Potent inducer of cytochrome P450 enzyme systemenzyme system

Rifampin decreases drug concentration of:Rifampin decreases drug concentration of:• alfentanil, amiodarone, anticoagulants (oral), atovaquone, alfentanil, amiodarone, anticoagulants (oral), atovaquone,

barbiturates, beta-blockers, buspirone, calcium channel barbiturates, beta-blockers, buspirone, calcium channel blockers, clarithromycin, oral contraceptives, corticosteroids, blockers, clarithromycin, oral contraceptives, corticosteroids, cyclosporine, dapsone, digoxin, disopyramide, HMG-CoA cyclosporine, dapsone, digoxin, disopyramide, HMG-CoA reductase inhibitors, azole antifungals, lamotrigine, losarten, reductase inhibitors, azole antifungals, lamotrigine, losarten, macrolides, methadone, morphine, NNRTIs, odansetron, macrolides, methadone, morphine, NNRTIs, odansetron, phenytoin, propafenone, protease inhibitors, quinidine, phenytoin, propafenone, protease inhibitors, quinidine, sirolimus, sulfonylureas, tacrolimus, theophylline, tricyclic sirolimus, sulfonylureas, tacrolimus, theophylline, tricyclic antidepressantsantidepressants

Rifampin concentration decreased by:Rifampin concentration decreased by:• protease inhibitorsprotease inhibitors

eCPS accessed 4/2/12

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IsoniazidIsoniazid Usual dose 300 mg daily (5 Usual dose 300 mg daily (5

mg/kg)mg/kg)

Inhibits mycolic acid synthesisInhibits mycolic acid synthesis

Profound early bactericidal Profound early bactericidal activity against rapidly dividing activity against rapidly dividing cellscells

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Isoniazid side effectsIsoniazid side effects Peripheral neuropathyPeripheral neuropathy

•Dose related side effect Dose related side effect •Vit B6 supplements to preventVit B6 supplements to prevent

Rare: seizuresRare: seizures +ANA antibodies in 20%, less than +ANA antibodies in 20%, less than

1% develop lupus1% develop lupus

*

INH HepatotoxicityINH Hepatotoxicity

HepatitisHepatitis• Incidence increases Incidence increases

with agewith age• Generally occurs Generally occurs

within weeks to within weeks to months rather than months rather than daysdays

• Takes weeks to Takes weeks to regress, recovery is regress, recovery is complete in most complete in most following drug following drug cessationcessation

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INH Drug InteractionsINH Drug Interactions

INH inhibits cytochrome P450 systemINH inhibits cytochrome P450 system Increase concentrations of:Increase concentrations of:

•carbamazepine, phenytoin, cycloserine, carbamazepine, phenytoin, cycloserine, theophylline, warfarintheophylline, warfarin

•These effects are offset with rifampinThese effects are offset with rifampin

•Check levelsCheck levels Also weak inhibitor of monoamine Also weak inhibitor of monoamine

oxidaseoxidase

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PyrazinamidePyrazinamide

Active against dormant and semi-Active against dormant and semi-dormant TB within macrophages or dormant TB within macrophages or in acidic environmentsin acidic environments

No proven benefit extending PZA No proven benefit extending PZA beyond 2 months in pts with beyond 2 months in pts with pansensitive TBpansensitive TB

No PZA No PZA → minimum of 9 months of tx→ minimum of 9 months of tx Dose is 25 mg/kg, requires renal dosingDose is 25 mg/kg, requires renal dosing

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PyrazinamidePyrazinamideside effectsside effects

HepatotoxicityHepatotoxicity•Actual incidence hard to predict as PZA Actual incidence hard to predict as PZA

always used with other TB meds, in one always used with other TB meds, in one study hepatotoxicity attributed to PZA in study hepatotoxicity attributed to PZA in 1%1%

•In the RZ studies for LTBI incidence os In the RZ studies for LTBI incidence os severe liver injury 5%severe liver injury 5%

RashRash Non gouty arthralgiasNon gouty arthralgias

•Seen in up to 40% of patients on daily ZSeen in up to 40% of patients on daily Z

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EthambutolEthambutol

Inhibits arabinosyl transferase Inhibits arabinosyl transferase (synthesis of TB cell wall (synthesis of TB cell wall component)component)

Less bactericidal compared to Less bactericidal compared to INH or RIFINH or RIF

Dose: 15 mg/kgDose: 15 mg/kg Requires renal dosingRequires renal dosing

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EthambutolEthambutolside effectsside effects

•retrobulbar neuritisretrobulbar neuritis Manifests as decreased visual acuity or Manifests as decreased visual acuity or

decreased red-green colour discrimination in decreased red-green colour discrimination in one or both eyesone or both eyes

Risk higher in pts with renal failureRisk higher in pts with renal failure

•Rarely used in children due to an Rarely used in children due to an inability to monitor for symptomsinability to monitor for symptoms

Duration of therapy in patients with Duration of therapy in patients with pansensitive strain of TBpansensitive strain of TB

Depends on location of TBDepends on location of TB• CNS involvementCNS involvement• OsteomyelitisOsteomyelitis

Was PZA used in first 2 monthsWas PZA used in first 2 months• NoNo→9 months of tx→9 months of tx

What were the culture results at 2 What were the culture results at 2 months?months?• positive→9 months of txpositive→9 months of tx

Duration of therapy = number of Duration of therapy = number of dosesdoses

Planned Planned durationduration

6 6 monthsmonths

9 9 monthsmonths

12 12 monthsmonths

Doses of 2/7 Doses of 2/7 INH/Rif in INH/Rif in continuationcontinuation

3636 6262 8686

Total DosesTotal Doses

3/7 intensive3/7 intensive6868 9494 118118

Total Doses Total Doses

5/7 intensive5/7 intensive8080 106106 130130

Monitoring for side effects during Monitoring for side effects during therapytherapy

ClinicalClinical• Screen for common side effectsScreen for common side effects

Microbiological responseMicrobiological response• Sputum at 2 months Sputum at 2 months • Sputum at completion of therapySputum at completion of therapy

Laboratory responseLaboratory response• First 2 weeks: twice weekly First 2 weeks: twice weekly • At 1 month then monthlyAt 1 month then monthly• Check: AST, ALT, Bilirubin, CBCCheck: AST, ALT, Bilirubin, CBC

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Adverse EffectsAdverse Effects

RifampinRifampin IsoniazidIsoniazid PyrazinamidePyrazinamide EthambutolEthambutol

• flushing, rashflushing, rash• increase in LFTs, increase in LFTs, hepatitishepatitis

• flu-like syndromeflu-like syndrome• hematologichematologic• body fluid body fluid discolorationdiscoloration

• increase in LFTs, increase in LFTs, hepatitishepatitis

• peripheral peripheral neuropathyneuropathy

• hepatitishepatitis• increased serum increased serum uric aciduric acid

• optic neuritisoptic neuritis

Common problems during therapyCommon problems during therapy

Nausea and vomitingNausea and vomiting Abnormal LFTsAbnormal LFTs DrowsinessDrowsiness Rash/puritisRash/puritis Missed dosesMissed doses

SYMPTOM MANAGEMENT:SYMPTOM MANAGEMENT:

Drowsiness:Drowsiness:• HS dosingHS dosing

Nausea:Nausea:• Have light food 30 – 60 minutes prior to DOTHave light food 30 – 60 minutes prior to DOT• Antiemetic 30 minutes prior to DOTAntiemetic 30 minutes prior to DOT• Stronger antiemetic/ranitidine/PPIStronger antiemetic/ranitidine/PPI

Rash/Itch:Rash/Itch:• Minor itchMinor itch continue meds with antihistamine continue meds with antihistamine

(usually RMP)(usually RMP)• Major rashMajor rash drug challenge after rest drug challenge after rest

• RMP/INH/EMB/PZA (usually PZA)RMP/INH/EMB/PZA (usually PZA)

HepatotoxicityHepatotoxicity Asymptomatic increases in LFTs occur in Asymptomatic increases in LFTs occur in

20% of pts on tx for TB20% of pts on tx for TB Most common serious side effectMost common serious side effect Defined as AST >5xULN or >3xULN with Defined as AST >5xULN or >3xULN with

symptomssymptoms Incidence depends on Incidence depends on

• AgeAge• Pre-existing liver diseasePre-existing liver disease• ETOH: appears to more than double risk of INH ETOH: appears to more than double risk of INH

hepatotoxiticityhepatotoxiticity INH more hepatotoxic than rifampinINH more hepatotoxic than rifampin

Nausea, vomiting, abdominal pain Nausea, vomiting, abdominal pain seen in 50-75% of patients with seen in 50-75% of patients with hepatotoxicityhepatotoxicity

Fever 10%, rash in 5%Fever 10%, rash in 5% Jaundice is a late findingJaundice is a late finding

What to do if a patient develops What to do if a patient develops abnormal LFTs on therapy?abnormal LFTs on therapy?

• AST/ALT 5X ULN asymptomatic orAST/ALT 5X ULN asymptomatic or• AST/ALT 3X ULN symptomatic orAST/ALT 3X ULN symptomatic or• JaundiceJaundice• → → HOLD TB Meds HOLD TB Meds • Once ALT returns to <2x ULN thenOnce ALT returns to <2x ULN then

Restart rifampin alone or with ethambutol, repeat ALT on day Restart rifampin alone or with ethambutol, repeat ALT on day 33

IF ALT <2x ULN then add in INH and repeat ALT in 3 daysIF ALT <2x ULN then add in INH and repeat ALT in 3 days Rechallenge with PZA may be hazardous and consider D/C Rechallenge with PZA may be hazardous and consider D/C

and extending tx to 9 monthsand extending tx to 9 months

RashRash

If minor, consisting of mainly puritis or If minor, consisting of mainly puritis or affecting limited areaaffecting limited area• → → trial antihistaminestrial antihistamines

Petechial rashPetechial rash• Check platelet countCheck platelet count

Generalized rash especially with fever or Generalized rash especially with fever or involving mucocutaneous areasinvolving mucocutaneous areas• → → hold all TB medshold all TB meds• Once rash subsides: restart drugs one by oneOnce rash subsides: restart drugs one by one• Rif → INH→ethambutol or PZA. If no rash with 3Rif → INH→ethambutol or PZA. If no rash with 3rdrd

drug then assume it is the 4drug then assume it is the 4thth drug that is the cause drug that is the cause

Manitoba Communicable Disease Control – Tuberculosis Protocol 2009

Missed dosesMissed doses

Paradoxical Reactions:Paradoxical Reactions:

Worsening of TB adenitis with Worsening of TB adenitis with development of new lymph nodes, development of new lymph nodes, increasing lymph node size or sinus increasing lymph node size or sinus drainagedrainage• Seen in up to 20% of patientsSeen in up to 20% of patients• Median time to onset: 1.5 monthsMedian time to onset: 1.5 months

Can present with new pleural Can present with new pleural effusions during trt for Pulm TBeffusions during trt for Pulm TB

Mgmt of Paradoxical Reactions:Mgmt of Paradoxical Reactions:

Rule out drug resistant TBRule out drug resistant TB Aspiration of lymph nodes, effusionsAspiration of lymph nodes, effusions

CorticosteroidsCorticosteroids• Unproven benefitUnproven benefit

NSAIDSNSAIDS

Treatment of patients in special Treatment of patients in special populationspopulations

Hepatic DiseaseHepatic Disease

Renal insufficiency/ESRDRenal insufficiency/ESRD

HIV infectionHIV infection Pregnancy/breastfeedingPregnancy/breastfeeding

Treatment in patients with pre-Treatment in patients with pre-existing liver diseaseexisting liver disease

Remember Remember ↑ AST/ALT may be ↑ AST/ALT may be secondary to TBsecondary to TB

If ALT more than 3xULN not related to TBIf ALT more than 3xULN not related to TB• Avoid PZAAvoid PZA

IF patient has cirrhosisIF patient has cirrhosis• Rifampin + ethambutol + fluoroquinolone Rifampin + ethambutol + fluoroquinolone

Severe liver disease with encephalopathySevere liver disease with encephalopathy• Ethambutol, fluoroquinolone, aminoglycoside Ethambutol, fluoroquinolone, aminoglycoside

(or capreomycin), cycloserine(or capreomycin), cycloserine

Renal insufficiency/ESRD:Renal insufficiency/ESRD:

Dose adjust Z and E if Dose adjust Z and E if CrCl<30ml/min or on PD or HDCrCl<30ml/min or on PD or HD

Intensive:Intensive:• INH/RMP OD post HDINH/RMP OD post HD• PZA/EMB 3X per week post HDPZA/EMB 3X per week post HD

ContinuationContinuation• INH/RMP 3X per week post HDINH/RMP 3X per week post HD

No data on peritoneal dialysisNo data on peritoneal dialysis

HIV infection:HIV infection:

CD4 count <200CD4 count <200• OD 7/7 X 2 months for intensive phaseOD 7/7 X 2 months for intensive phase• 3X per week for continuation phase3X per week for continuation phase

Protease inhibitor interaction with Protease inhibitor interaction with RifampinRifampin Rifabutin in consultation with Rifabutin in consultation with HIV pharmacistHIV pharmacist

Starting of ART (on new HIV DX)Starting of ART (on new HIV DX)• Dependent on CD4 countDependent on CD4 count

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TB and HIV Drug InteractionsTB and HIV Drug Interactions Rifampin and Protease inhibitorsRifampin and Protease inhibitors (PI) (PI)

• Effect: Decreased PI serum levelsEffect: Decreased PI serum levels• Substitute Rifampin with Rifabutin 150 mg po Substitute Rifampin with Rifabutin 150 mg po

thrice weekly (may need to increase to 300 mg thrice weekly (may need to increase to 300 mg thrice weekly or 150 mg po daily)thrice weekly or 150 mg po daily)

Rifampin and EfavirenzRifampin and Efavirenz• Effect: Decreased efavirenz levelsEffect: Decreased efavirenz levels• Increase efavirenz dose to 800 mg po daily Increase efavirenz dose to 800 mg po daily

(usual 600 mg daily)(usual 600 mg daily) Rifampin and RaltegravirRifampin and Raltegravir

• Effect: Decreased raltegravir levelsEffect: Decreased raltegravir levels• Increase raltegravir to 800 mg po BID (usual Increase raltegravir to 800 mg po BID (usual

dose 400 mg po BID and continue higher dose dose 400 mg po BID and continue higher dose for at least 2 weeks post completion of for at least 2 weeks post completion of Rifampin)Rifampin)

Pregnancy:Pregnancy:

TB not an indication for pregnancy TB not an indication for pregnancy terminationtermination

First line drugs safe in pregnancy (H,R,E)First line drugs safe in pregnancy (H,R,E)• PZA: limited data with respect to teratogenic PZA: limited data with respect to teratogenic

effects. Recommended by WHO and IUATLDeffects. Recommended by WHO and IUATLD

Fluoroquinolones and aminoglycosides Fluoroquinolones and aminoglycosides contraindicated while pregnantcontraindicated while pregnant

Breastfeeding Moms:Breastfeeding Moms:

11stst line drugs line drugs• Very small concentrations in breast milk Very small concentrations in breast milk • Encourage breast feedingEncourage breast feeding• Have not shown to produce toxic effects in Have not shown to produce toxic effects in

newbornnewborn• Mum should be on pyridoxine supplementsMum should be on pyridoxine supplements• Drugs level in breast milk not sufficiently high Drugs level in breast milk not sufficiently high

to be considered effective tx for infantto be considered effective tx for infant

Certain 2Certain 2ndnd line drugs not recommended - line drugs not recommended - data unknowndata unknown

Concerns re poor absorption:Concerns re poor absorption: Consider if significant malnutrition, diabetic gastroparesis, Consider if significant malnutrition, diabetic gastroparesis,

HIV, underlying GI disease, treatment failureHIV, underlying GI disease, treatment failure INH/RMP serum levels:INH/RMP serum levels:

• Usually 2 hours (+/- 6 hours) post oral drug adminUsually 2 hours (+/- 6 hours) post oral drug admin• Special lab handlingSpecial lab handling• Done in Mayo Clinic (Rif) and in Ontario Lab (INH) results take Done in Mayo Clinic (Rif) and in Ontario Lab (INH) results take

~ 2-3 weeks ~ 2-3 weeks

Available IV drugs include INH, RIF, fluoroquinolones, Available IV drugs include INH, RIF, fluoroquinolones, aminoglycocidesaminoglycocides

Recommendations-Parental route (delays discharge)Recommendations-Parental route (delays discharge)• Only select drugs via Home Care/Mount Carmel Clinic/Lions Only select drugs via Home Care/Mount Carmel Clinic/Lions

Place in WRHAPlace in WRHA

Drug resistanceDrug resistance

Primary versus acquiredPrimary versus acquired PZA resistance: treat for 9 months PZA resistance: treat for 9 months INH monoresistanceINH monoresistance

• 6 month R,Z,E6 month R,Z,E• 12 months of 2RZE/10RE12 months of 2RZE/10RE

MDR= resistance to INH and RIFMDR= resistance to INH and RIF

MDR =failure of public healthMDR =failure of public health

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Second Line*Second Line*

FluoroquinolonesFluoroquinolones• CiprofloxacinCiprofloxacin• LevofloxacinLevofloxacin• MoxifloxacinMoxifloxacin

AminoglycosidesAminoglycosides• AmikacinAmikacin• StreptomycinStreptomycin• CapreomycinCapreomycin• KanamycinKanamycin

RifamycinsRifamycins• RifabutinRifabutin• Rifapentine**Rifapentine**

EthionamideEthionamide CycloserineCycloserine Para-amino-Para-amino-

salicyclic acid salicyclic acid (PAS)(PAS)

ClofazimineClofazimine

**not commercially available

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Third LineThird Line

Amoxicillin/clavulanateAmoxicillin/clavulanate Imipenem/cilastatinImipenem/cilastatin LinezolidLinezolid ClarithromycinClarithromycin ThiacetazoneThiacetazone

Management of MDR-TBManagement of MDR-TB Individual regimes guided by DSTIndividual regimes guided by DST

• Ask yourself: could the DST pattern have changed due to tx Ask yourself: could the DST pattern have changed due to tx during the interval from sputum collection to obtaining DST?during the interval from sputum collection to obtaining DST?

Management of MDR-TBManagement of MDR-TB

Injectable: used daily for first 2-6 Injectable: used daily for first 2-6 months then can be stepped down to months then can be stepped down to 3x/week, ideally for >6 months3x/week, ideally for >6 months

Must have daily directly observed Must have daily directly observed therapy for the duration of therapytherapy for the duration of therapy

Duration: 18-24 months after sputum Duration: 18-24 months after sputum conversionconversion

Surgery in MDR TB-it’s backSurgery in MDR TB-it’s back

Objectives:Objectives:

• Become familiar with the first and Become familiar with the first and second line anti-tuberculosis antibiotics second line anti-tuberculosis antibiotics and the standard treatment regimesand the standard treatment regimes

• Identify the common adverse effects Identify the common adverse effects and drug interactions associated with and drug interactions associated with these antibioticsthese antibiotics

• Describe problem-solving techniques Describe problem-solving techniques that are used to help identify and that are used to help identify and manage common adverse effectsmanage common adverse effects

Take home pointsTake home points Duration of tx depends on results of 2 Duration of tx depends on results of 2

month cultures and the inclusion of PZAmonth cultures and the inclusion of PZA Treatment completion depends on the Treatment completion depends on the

number of doses taken not duration of txnumber of doses taken not duration of tx Many side effects do not require Many side effects do not require

discontinuation of txdiscontinuation of tx Beware of drug-drug interactionsBeware of drug-drug interactions Hepatotoxicity is the most common Hepatotoxicity is the most common

serious side effect requiring serious side effect requiring discontinuation of drugdiscontinuation of drug• Introduce Rif then INH once LFTs return to Introduce Rif then INH once LFTs return to

normalnormal

Questions or Comments?Questions or Comments?

References:References:

Manitoba Health(Dec 2009)Tuberculosis Manitoba Health(Dec 2009)Tuberculosis ProtocolProtocol

Public Health Agency of Canada (2007) Public Health Agency of Canada (2007) Canadian TB Standards 6Canadian TB Standards 6thth Edn p.117 – Edn p.117 – p.119, p.122 – p.128, p.130, p.161 – p.163, p.119, p.122 – p.128, p.130, p.161 – p.163, p.206 – p.209p.206 – p.209

MMWR June 20, 2003MMWR June 20, 2003 WHO guidelines 2009WHO guidelines 2009

56Saukkonen et al. Am J Resp Crit Care Med 2006