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IntroductionPatients on treatment for drug-resistant tuberculosis (DR-TB) face many challenges,most notably difficult side effects such as nausea, hearing loss and fatigue thatmay impact the patient’s quality of life, capacity to work and ability to continue activities of daily living. Recent studies have identified medication side effects as a majorfactor for patients stopping treatment prematurely. The 2017 WHO Global TB Reportnoted a continued crisis related to treatment outcomes for drug-resistant TB withonly 54% of patients successfully completing treatment in 2014.Nurses are frequently the first point of contacta patient will have when seeking health careand are the main cadre of health professionalsworldwide delivering and/or overseeing apatient’s daily directly observed treatment.Nurses are often the first to hear of a patient’s side effect(s) during TB treatment andtherefore, are well positioned to intervene. In response to requests from nurses foradditional nursing practice resource tools, this guide was developed to help nursesassess for and respond appropriately to side effects related to anti-TB medications.The guide is designed as a reference so nurses can quickly:1. Identify symptoms that may indicate an anti-TB or anti-retroviralmedication-related side effect;2. Assess for severity as well as other potential contributors; and3. Intervene appropriately to minimize patient discomfort, reduce sideeffect progression, and ultimately support successful treatmentcompletion.This guide was developed by nurses with experience in the clinical care and programmatic management of TB and DR-TB in both high- and low-resource settings. Nursingand DR-TB literature were reviewed to establish best practice nursing assessmentand intervention guidance. Nurses caring for patients with DR-TB field tested the job aidand provided feedback which was used to inform final content and format.8N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

How Information is OrganizedThe guide is organized into the major types of toxicities, the associated symptoms, possible offending medications, and the suggested nursing assessments and interventions. Some symptoms ( e.g. nausea) may be associatedwith a number of underlying causes and may be mild, or a symptom of amore serious medical situation requiring urgent attention. The pathophysiology for medication-related fatigue and hypersalivation are unclear and thesesymptoms are not grouped under a specific type of toxicity. Additional information (comments) are provided for each toxicity to highlight relevant clinical information that may assist in management of side effects. Medications morestrongly associated with the side effect appear in bold text. The appendicesinclude tools nurses can use to more thoroughly assess patient complaints ofpain, depression and neuropathy.How to Use the GuideThe guide is a practical resource for nurses in inpatient, clinic and communitysettings and may be used in conjunction with local protocols. Some assessments and interventions may not be available or within the scope of practicein all settings; nurses should refer to local protocols when available to guidedecision-making. The scope of this guide is limited to address management ofmedication-related side effects and does not address management of symptoms due to the disease itself or other important aspects of nursing care (suchas addressing barriers to adherence). Additionally, the guide does not replacethe need for training and mentoring for nurses caring for patients with DR-TB.We encourage our nurse colleagues to continue to identify gaps in resourceand training materials so that we can work to address the needs. Please contact the authors if you have questions.N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T9

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GastritisDiarrheaGastrointestinalNausea and Vomiting11

Gastrointestinal / Nausea & VomitingSymptomsNursing AssessmentNausea and/orvomitingPossible dqNVPInhand mostothersEmbPzaAmx /ClvCfzDlmLzdCs / Trd12Observe for signs of: Hepatitis (fatigue, abdominal pain, yellowingof eyes and skin) GI bleeding (vomit with red blood or “coffeeground” appearance, abdominal pain,dizziness) Dehydration (dry/tenting of skin, sunkeneyes, decreased urination, confusion)Ask the patient: What medicines are you taking? When does the nausea or vomiting start? How often do you experience the nauseaand/or vomiting and how long does it last? What makes it better or worse? How is your appetite? What have you had to eat/drink today? If vomiting, describe color and consistencyIf significant vomiting, check: Vital signs, serum electrolytes and creatinine If febrile, refer for medical evaluationN U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

Seek urgent medical evaluation when signs of hepatitis, GI bleeding ordehydration are observed.NAUSEA & VOMITINGNursing InterventionsCounsel the patient: Some nausea and vomiting is expected early in DR-TB treatment but willdecrease over time Nutrition support strategies (e.g., good hydration; small, frequent meals; gingerdrinks or sweets may help) Relaxation techniques or other comfort measuresWhen nausea and/or vomiting is considered troublesome to the patient,discuss with the doctor: Anti-emetic* 30 min. before DR-TB medication Slow ramping up of suspect medication (Eto/Pto, PAS) Timing of suspect medication dose (larger dose at bedtime or different time of day) Anti-anxiety medication for anticipatory nausea Whether oral or IV rehydration needed if patient shows signs of dehydration Whether electrolyte replacement is indicatedCommentsNausea and/or vomiting may also occur with: Acute viral illnessHepatitisGastritis or peptic ulcerPancreatitisDisease of the gall bladderDisease of the bile ductsLactose intoleranceAcute renal failureAlcohol withdrawalDiabetic gastroparesisPregnancyBowel obstructionCNS TBPsychological factors (e.g., anxiety)Patients with diabetes may have betterresults with promotility medication (e.g.,metroclopramide).Note:*If patient is taking Bdq or Dlm,do not give ondanestron as ananti-emetic as it mayprolong QTc.N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T13

Gastrointestinal / GastritisSymptomsNursing AssessmentOne or more of thefollowing symptoms:Pain or burningsensation inabdomen oresophagusSour taste inmouthBloatingObserve for signs of: Hepatitis (fatigue, abdominal pain, yellowingof eyes and skin) GI bleeding (blood in vomit or stool)Ask the patient: What medicines are you taking? When do the symptoms occur? How long does it last? What makes it better or worse? How is your appetite? What have you had to eat/drink today?Possible OffendingMedicationsAnti-TB:ARVs:PASMost ARVsCheck for symptoms of gastritis (epigastricburning, sour taste in mouth, abdominaldistention or bloating)Eto/PtoCfzFQs (Lfx, Mfx)InhEmbPza14N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

GASTRITISNursing InterventionsSeek urgent medical evaluation when signs of hepatitis or GI bleeding (presenceof blood in vomit or stool) are observed.Counsel the patient: Gastritis is a common side effect of DR-TB treatment and can be treated Try eating small, frequent meals. Avoid food and drink that may make symptomsworse (e.g., alcohol, caffeine, spicy, acidic, high fat) Try relaxation and/or distraction techniquesWhen gastritis is troublesome, discuss with the doctor: Whether use of adjuvant medication (H2-blocker or proton-pump inhibitor)may help Minimize or discontinue use of NSAIDs Starting an antacid; NOTE: antacids must be taken 2 hours before or afterTB medicationsCommentsSymptoms are often worse in the morning orprior to eating. Patients who take nonsteroidalanti-inflammatory drugs (NSAIDs) or drink a lotof alcohol are at increased risk.Abdominal pain is a common side effect ofARVs.Abdominal pain can also occur with pancreatitis,lactic acidosis, infection with H. pylori andpeptic ulcer.Cfz has been associated with severe abdominaldistress. In such cases, Cfz should be stopped.If patient is taking the short DR-TB regimenwhich includes Cfz and must stop due to thisadverse effect, the patient no longer qualifies tocomplete the shorter regimen and must switchto an alternative DR-TB regimen.N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T15

Gastrointestinal / DiarrheaSymptomsNursing AssessmentFrequent and/orloose stoolMay be accompanied by:Abdominalcramping When did this start?Anti-TB:ARVs:PASAll PIsEto/PtoddI(bufferedformulation)Lzd Dehydration (dry/tenting of skin, sunkeneyes, decreased urination, confusion, fatigueand extreme weakness)Ask the patient:Possible OffendingMedicationsFQs (Lfx, Mfx)Observe for signs of: How many times a day are you passingstool? What makes it better or worse? What does the stool look like? Is there blood or mucous in the stool?If yes, refer immediately for medicalevaluationCheck: Vital signs — if febrile, refer for medicalevaluationAmx /Clv16N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

DIARRHEANursing InterventionsSeek urgent medical evaluation when signs of dehydration are observed.Counsel the patient: Loose stools are common early in DR-TB treatment but usually resolve aftera few weeks Drink plenty of fluids throughout the day Avoid high fiber or fatty/fried foods Probiotic products (with Lactobacillus) or foods such as yogurt (not givenwithin 2 hours of the FQ) may improve symptoms by replacing normal flora/gutbacteriaWhen diarrhea is considered troublesome to the patient, discuss with thedoctor: Use of adjuvant medication (loperamide) Slow ramping up of the suspect medication (PAS) Dose reduction of suspect medication if it would not compromise the regimenCommentsDiarrhea related to PAS usually improves aftera few weeks on DR-TB treatment.Diarrhea related to Lzd use may resolve with adose reduction.The presence of fever or blood in the stoolsuggests diarrhea may be due to a cause otherthan the anti-TB medications or ARVs.Diarrhea may also occur with: Inflammatory bowel disease Waterborne bacterial andparasitic infections Clostridium difficile(pseudomembranous colitis) Lactose intoleranceN U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T17

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Hepatoxicity19

HepatoxicitySymptomsNursing AssessmentNausea, vomiting PL U SAbdominal pain,fatigue, and lossof appetite.Later stage symptomsmay include:Same observations and questions forassessing nausea and vomiting PLUS: Observe for signs of jaundice(yellowing of the skin and whites of the eyes) Use pain assessment approach whenpatient reports pain (see Appendix A)Ask the patient: Do you drink alcohol?If yes, how much, how often and when wasyour last drink?FeverRashJaundice(yellowing of the eyesand skin)Check: Latest liver function test (LFT), total bilirubin,serum albumin and electrolytes Viral hepatitis panel resultsPossible s(TPV/r others)RfbEto/PtoBdq Urine and stool color Patient’s nutritional status (weight and BMI)and nutritional intakemost NRTIs(d4T, ddl, AZT)PASRarely,Emb andMfx20N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

Seek urgent medical evaluation when these symptoms are present togetherand/or if liver enzymes are greater than or equal to 5 times the upper limit of normal.H E PAT O X I C I T YNursing Interventions Stop all anti-TB medications and other hepatotoxic medications Evaluate and treat other potential causesCounsel the patient: Comfort measures to minimize pain Limited activity to conserve energy Frequent small meals to maintain optimal energy metabolism Avoid alcoholDiscuss with the doctor: Whether oral or IV rehydration needed if patient shows signs of dehydration Nutrition consult if available Whether blood tests should be done /repeated (LFT, total bilirubin, albumin,viral serology) Plans for re-introduction of TB medications and whether to discontinue likelyoffending medicationsCommentsAbdominal pain may be an early symptomof severe side effects, such as pancreatitis,hepatitis or lactic acidosis.HIV coinfection may increase risk of hepatitis.Other medications may also contribute (e.g.,TMP/SMX, ibuprofen, acetaminophen).Viral causes of hepatitis (hepatitis A, B, C, andcytomegalovirus) should be evaluated.EFV, NVP and TPV/r are not recommended inpatients with HIV and hepatic insufficiency.N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T21

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Musculoskeletal23

MusculoskeletalSymptomsNursing AssessmentMuscle pain orjoint painObserve for signs of acute swelling, erythemaand warmth at the site of muscle or joint pain.Ask the patient:Possible OffendingMedicationsAnti-TB:ARVs:PzaIndinavirFQs (Lfx, Mfx)other PIsEto/PtoBdq What medicines are you taking for themuscle or joint pain? Any past medical history of joint or musclepain? Use pain assessment questions inAppendix ACheck: TSH, serum electrolytes and uric acidblood testsRfb24N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

Nursing Interventions Acute swelling, erythema, and warmth are present to evaluate for infection orinflammatory disease TSH, electrolytes or uric acid blood tests are abnormalCounsel the patient:M U S C U L O S K E L E TA LSeek further medical evaluation if: Some pain/tenderness of muscles and joints is common during first weeks oftreatment but will decrease over time Avoid vigorous physical activity if there is Achilles’ tendon tenderness Physical activity as tolerated may help decrease the pain Low-purine diet may help if pain is due to gout (e.g. avoid meats high in purinesuch as liver and kidney; limit intake of red meat, poultry and fish) Importance of keeping well-hydratedWhen a patient experiences or is troubled by muscle or joint pain, discusswith the doctor: Use of ancillary analgesic /NSAIDsCommentsProtease inhibitors can cause joint pain andrarely, more severe rheumatologic pathology.Tendon rupture associated with FQ use is rare;older patients and those with diabetes may havegreater risk.Electrolyte disturbances associated with theaminoglycosides and Cm may also causemuscle pain and cramping.Hypothyroidism may also contribute.Pza may need to be stopped in order to relieveacute gout related to this medication.N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T25

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Fatigue27

FatigueSymptomsGeneral feelingof tirednessLack of energyPossible OffendingMedicationsNursing AssessmentObserve for signs of fatigue such as decreasedability to perform usual activities and functions ofdaily living.Ask the patient: When did you begin to notice a change inyour energy? What is the pattern and duration of yourfatigue during the day? What makes it better or worse?Anti-TB: What have you had to eat and drink today?Any drug What is your sleep pattern? Do you feel you are getting enough sleep?Check: Underlying causes of fatigue includinganemia, sleep disturbance, nutritional orelectrolyte imbalances, hypothyroidism andlactic acidosis28N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

Nursing InterventionsSeek further medical evaluation if there is evidence of specific contributing factorsincluding pain, emotional distress, anemia, electrolyte imbalance or hypothyroidism. Self-monitor fatigue levels and use strategies for energy conservation Consider exercising as toleratedFAT I G U ECounsel the patient: Maintain good nutritional diet Importance of adequate sleepDiscuss with doctor: Treatment for underlying causes Whether medications can be given later in the day or evening to minimizeimpact of fatigueCommentsFatigue can be a distressing and disruptivesymptom that may be under-reported andunder-treated.Fatigue is rarely an isolated symptom and mostcommonly occurs with other symptoms suchas pain, emotional distress, nausea, and sleepdisturbance.Fatigue may be related to TB disease itself,medication side effects or otherco-morbidities.N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T29

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Ototoxicity andVestibular ToxicityPeripheral ogicalOptic Neuritis31

Neurological / Optic NeuritisSymptomsNursing AssessmentVision changes(color and acuity)Observe for signs of acute vision changes.Ask the patient:Pain around theeye or with eyemovement Any changes or problems with your eyesight?If so, describe the changes you’ve noticed. Are you having any eye pain?Check:Possible OffendingMedicationsAnti-TB:ARVs:Embddl Visual acuity and color vision Serum glucose and HgbA1c Creatinine clearanceLzdEto/PtoRfbCfz and Inh(rare)32N U R S I N G G U I D E F O R M A N A G I N G S I D E E FF E C T S T O D R U G - R E S I S TA N T T B TR E AT M E N T

Nursing InterventionsSeek medical evaluation for acute vision changes or eye pain.Counsel the patient (and family): To watch for and report any vision changes or eye pain Importance of ensuring safe environment for patient with visual impairment Importance of keeping blood glucose in a healthy range if patient also hasdiabetesDiscuss with the doctor: Whether referral for ophthalmologist evaluation may be indicated Whether suspected offending medication should be discontinued and replacedOPTIC NEURITIS Avoid vigorous exercise until condition is evaluated Frequency

Nursing Association and Peking Union Medical College School of Nursing (Dr Zhao Hong and Dr Guo Aimin), Indonesia (National TB Program and Challenge TB KNCV Indonesia with Dr Astuti Nursasi), South Africa (Ms Sharon Fynn), Ghana National TB Control Programme (Dr Nii Nortey Han-son-Nortey),