Ready Reckoner for Medical Officers / General Practitioners

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Ready Reckoner for Medical Officers / General Practitioners

Side effects associated with anti-TB drugs and their prevention and management

Important general instructions

ADRs with anti-TB drugs, their prevention and management
Laboratory test for TB patients
Warning Symptoms for some serious adverse reactions

Absolute contraindications of anti-TB drugs: (Benefit - Risk have to be carefully assessed)
Algorithm for reintroduction of anti-TB drugs -To be done by experts only

Stepwise increase in the dosage for Reintroduction
Anti-TB drugs in pregnant & lactating women

Pregnancy
Lactation

Contraception
Anti-TB drugs in renally impaired patients
Commonly used ancillary medicines

Side effects associated with anti-TB drugs and their prevention and management

Important general instructions

Ensure that patient completes full course of anti-TB therapy
Side effects of anti-TB drugs can be an important cause of patient stopping medication, especially with second line drugs
Prevention and early detection of side effects are needed
Alcohol, smoking and use of illicit drugs increase side effects
Relevant history, clinical examination and lab tests are important to evaluate risk factors and diagnosis of side effects at an early stage
For contraception, ask patient to seek advice from family planning center as oral contraceptives are less effective with some anti-TB drugs
Educate, counsel and reassure patients for self-limiting side effects
For side effects and serious side effects, take immediate action and refer patients to specialist as suggested below
Report serious side effects to PvPI center (Procedure for reporting: Call your nearby PvPI center and provide complete information about side effect. (National toll free number: 18001803024)
Advice nutritious diet to TB patients
Advice patients about respiratory hygiene and provide information on preventing spread of TB (Cover nose and mouth with facemask, tissue paper)

ADRs with anti-TB drugs, their prevention and management

ADRs	Diagnosis	Suspect Drug(s)	Differential Diagnosis/Other causes	Prevention	Management
Nausea and Vomiting	Clinical, based on complaints by patient	All oral anti-TB drugs	Hepatitis	Take anti-TB medication with banana	Symptomatic management.Exclude hepatitis / hepatoxicity
Rash, urticaria	Clinical	All anti-TB drugs	Steven Johnson syndrome, Anaphylactic reaction, Exfoliative dermatitis, Herpes infection	Seek past history allergy before starting treatment and as applicable	If rash involves <10% body drugs surface area (BSA) and is not with mucous membrane involvement, treat with anti-histaminics. Stop suspect anti-TB drug and refer patient to specialist if indicated. Desensitization can be attempted. If it fails, substitute the suspect drug with alternate drug
Diarrhea	Clinical	All oral anti-TB drugs	Bacterial dysentery,Amoebic dysentery, Malabsorption syndrome, Pseudomembranous colitis	Use of clean and potable water for drinking, washing hands before eating and drinking any thing	Advice Oral Rehydration Solution (ORS) 200 ml, after each loose stool. Check for any infective causes.
Liver enzymes- SGOT/SGPT (AST/ ALT) increased (up to 2xULN)	Increase of liver enzymes after starting anti-TB drugs	Frequent & Severe: PZA, INH, RIF Rare: EMB, Ethionamide, Fqs, PAS, Cycloserine	Viral hepatitis-rule out by negative serological tests for A,B,C and E Alcoholic hepatitis- AST:ALT>2:1 with history of alcoho intak Amoebic liver abscess- Ultrasound/CT to detect cystic lesions /abscess Mass in ultrasound/CT -> Liver biopsy to rule out Hepatoma	Up to 2xULN is not serious. Drug induced hepatitis is reported in 8-30 of patients. Avoid simultaneous administration of other hepatotoxic drugs It can worsen to severe hepatitis, which can be prevented by monitoring of LFT in high risk patients every 15 days & taking appropriate action if liver enzymes increase.	Usually drugs are not withdrawn. Check for other potential hepatotoxic agents e.g alcohol
Hepatitis(Severe)	ALT/AST > 3x ULN with symptoms of Nausea, vomiting, anorexia, jaundice, dark colored urine OR ALT/AST > 5xULN without symptoms	Frequent & Severe: PZA, INH, RIF Rare: Ethionamide, PAS, Cycloserine Clarithromycin Clofazimine Imipenemcilastatin	Investigate as above to rule out: Viral hepatitis, Alcoholic hepatitis, Amoebic liver abscess, Hepatoma	Early detection of raised liver enzymes to prevent worsening & reduce associated morbidity & mortality	Management includes withdrawal of potential causative drugs & supportive treatment.Later,when enzymes level return to normal, then gradually reintroduce the drugs (Refer to flowchart)
Exfoliative and allergic dermatitis	Clinical based on symptoms- Pruritus, widespread erythema and epidermal sloughing	Frequent : FAQ Rare: RIF, PAS Cycloserine linezolid Amoxicillin clavulanate clarithromicin Clofazimine	Asteatotic Eczema, Contact Dermatitis,Drug-Induced Bullous , Disorders, Drug-Induced Photosensitivity, Nummular Dermatitis, Perioral Dermatitis,Phytophotodermatitis	Early detection and management can prevent worsening antihistamines	Topical hydrocortisone or oral may be helpful to Pruritus, Anti-TB widespread RIF medications should not be discontinued unless an equally effective drug is available for substitution.Refer to specialist if indicated
Stevens-Johnson and Toxic epidermal necrosis	Clinical based on total body surface area (BSA) involvement of more than 10% and/or mucous membrane involvement	Rare: INH, RIF, EMB, Fqs, Amoxicillin-clavulanate clarithromycine imipenem-cilastatin	Staphylococcal scalded skin syndrome, Irradiation-History of radiation, Trauma-History, Progressive systemic sclerosis - ANCA antibodies.	Early detection and management can prevent worsening	Immediate drug withdrawal and referral to specialist is recommended. Supportive therapy like antihistamines, anti-inflammatory agents may be helpful in the meantime
Psychosis (Severe)	Symptoms of Hallucinations, paranoia, suicidal or abnormal thoughts or actions	Frequent & Severe: Cycloserine Frequent: INH Rare: RIF, FQs Clarithromycin Clofazimine Imipenem-cilastatin	Post-traumatic Stress Disorder, Delusional disorder, Schizophrenia, Schizophreniform Disorder	Careful monitoring. Psychiatric counseling at the start of treatment in patients at risk of psychiatric disorders.	Refer to specialist for further evaluation Consider suspect drug withdrawal. Refer to specialist
Peripheral neuropathy	Clinical symptoms of Burning and paresthesia in extremities. Electromyography (nerve conduction studies) for confirmation	Frequent: INH Rare:EMB, FQs, PAS, Ethionamide Cycloserine Linezolid (severe)	Neuropathy due to high dose of pyridoxine Diabetic neuropathy Peripheral demyelinating disease	Supplementing the anti- TB drugs with Pyridoxine 5-10 mg orally once a day while patient is on INH Pyridoxine 50 mg per day with Linezolid and with every 250 mg Cycloserine	Check for Pyridoxine compliance. Give paracetamol / NSAIDs to alleviate pain. Drug withdrawal is not indicated. Start Pyridoxine 100 mg per day. If no response, increase dose of Pyridoxine to 200 mg. Refer to specialist if no response or if patient is taking Linezolid.
Ototoxicity/ Hearing loss/Deafness	Symptoms- Tinnitus, vertigo, Loss of balance and equilibrium. Audiometry for confirmation	Frequent & Severe: AGs Rare:Linezolid clarithromycin imipenem-cilastatin	Ear wax, otitis media, Traumatic hearing loss, Meniere's disease Acoustic neuroma	Monitoring of early symptoms can prevent permanent ear damage	Consider withdrawal of the suspect drug. Refer to specialist for further evaluation
Optic neuritis	Vision loss, Peri- ocular pain, Dyschromatopsia (disorder of color vision), based on symptoms and ophthalmic examination for confirmation	Frequent & Severe: EMB Rare: PAS Ethionamide Clofazimine Linezolid	Brain Tumor, Giant cell arteritis, Retinal detachment, Multiple sclerosis, Closed-angle glaucoma, Cataract, Macular degeneration, Diabetic retinopathy	Regular ophthalmologic examination	Consider withdrawal of the suspect drug. Refer to specialist for further evaluation
Immune Nephrotoxicity	Serum creatinine >2xbaseline. Presence of Auto- antibodies in the blood is confirmatory	RIF, especially when restarted after stopping for few weeks	Urinary tract infection, Post streptococcal glomerulonephritis, Minimal change disease, Rapidly progressing glomerulonephritis	Patients should be counseled not to stop and restart rifampicin randomly, on their own	Consider drug withdrawal and refer to specialist
Flu Syndrome	By symptoms- Chills, malaise, dry cough, shortness of breath, loss of appetite, body aches and nausea	Frequent: RIF - Specially with alternate day regimen	Viral infections: Influenza, Dengue Fever: Dengue NS1 antigen test positive	Patients on daily regimen have reported lower frequency and less severe flu as compared to the patients on intermittent regimen	Oral antihistaminics and paracetamol, according to the symptoms
Arthralgia / Arthritis	Joint pain, swelling involving one or more joint. High uric acid levels, demonstration of tophi crystals in joint is confirmatory of Gout	Frequent & Severe: PZA Rare: EMB, INH	Osteoarthritis, Rheumatoid arthritis	Early diagnosis and management can prevent progression and can improve quality of life	Therapy with paracetamol / NSAIDs can be used for pain relief as needed / Colchicine can be given in gout.
Thrombocytopenia	Blood platelet count <50000 /mm³ indicates thrombocytopenia, Drug induced thrombecytopenia is diagnosed by excluding other causes of thrombocytopenia	Frequent & Severe: RIF, FQs Rare: INH, EMB, PZA, AGs, PAS, Ethionamide Cycloserine Amoxicillin- clavulanate -Clarithromycin Imipenemcilastatin Linezolid	Dengue hemorrhagic fever - Dengue NSl antigen test positive Malaria - Peripheral blood smear, malaria antigen test Liver Cirrhosis - Liver Biopsy Thrombotic Thrombocytopenic Purpura Blood picture showing thrombocytopenia and hemolytic anemia with clinical symptoms Acute Leukemia - Bone marrow examination	Patients should be advised not to skip the doses of anti-TB drugs as the incidence of drug- induced thrombocytopenia has been reported to be higher when the drug is not taken continuously Regular monitoring of platelet levels can facilitate early detection & thus, reduce the associated morbidity & mortality	Manage with platelet transfusion and consider withdrawal of suspect drug. It is important to remember that anti-TB drugs can cause thrombocytopenia.
Leucopenia	Leucocyte count Iess than 2000/mm ³ Neutropenia : Absolute neutrophil count less than 1000/mm³ Routine blood counts	Rare: INH, EMB, RIF, FQs, AGs, Ethionamide Linezolid Amoxicillin Clavulanate Clarithromycin Imipenem-cilastatin	Typhoid, malaria, dengue, Rickettsial infections, HIV, thyroid disorders., aplastic anemia, rheumatoid arthritis, vitamin BI2 or folate deficiency, mineral deficiencies of copper and zinc. Bone marrow diseases: Myelodysplastic syndrome, leukemia, Autoimmune disorders: SLE, Bone marrow damage or suppression Drug induced Leucopenia, Clozapine, Valproate, Lamotrigine,Interferons and Bupropion	Monitoring of the complete blood count as indicated, will help in early identification. Avoid simultaneous administration of other drugs that can cause leucopenia.	If the total leucocyte count is <2000/ mm³ or absolute neutrophil count <1000/mm³. Refer the patient to specialist as this is serious.
Nephrotoxicity	Serum creation more the twice the baseline with symptoms of Oliguria, loss of appetite, General ill feeling and fatigue	Frequent & Severe: AGs Rare: Linezolid	Chronic renal failure, Alcoholic keteacidosis, Diabetic keteacidosis, Metabolic acidosis, Urinary tract infection	Dose adjustment in patients with pre- existing renal disease, monitoring of renal function as indicated	Dose adjustment in patients with pre-existing renal disease. In cases of lack of response consider drug withdrawal and refer to specialist.
Hyperglycemia	Fasting blood sugar more than 160 mg/dl with polydypsia, polyphagia, polyuria	Rare: RIF, INH FQs, Moxifloxacin Clofazimine	Uncontrolled diabetes mellitus, Impaired glucose tolerance	Regular Blood sugar monitoring in high risk patients can help in early detection.	Individualized diet, exercise, patient education and glucose-lowering therapies.
Hypoglycemia	Blood sugar less than 55 mg/dl with weakness, palpitation, loss of consciousness, seizures	Rare: INH Ethionamide Clarithromycin	Prolonged starvation, Overdose of insulin or oral hypoglycemic agents in diabetic patients	Regular Blood sugar monitoring in high risk patients for early detection	In case of severe hypoglycemia, withhold all hypoglycemic medications. Glucose to be given orally or I.V as appropriate.
Hypothyroidism	TSH level >10 mIU/L with tiredness, increased sensitivity to cold, weight gain, constipation, depression, lethargy	Rare: PAS Ethionamide Cycloserine	Hypothyroid Goitre - TSH levels high Myxoedema - Hashimotos thyroiditis - Anti-thyroid antibodies Riedels thyroiditis -Antibodies	Early diagnosis, followed by prompt treatment can help to prevent worsening.	All patients with TSH >10 mIU/L, whether symptomatic or not, should be started on Levothyroxine
Pseudomembrano us colitis	Watery diarrhoea with or without blood, associated with stomach cramps and high fever, stool examination	Frequent & Severe: Amoxicillin - clavulanate Clarithromycin Imipenem-cilastatin Linezolid Rare:RIF, FQs	Viral diarrhea, Bacterial diarrhea, Amoebic dysentery, Malabsorption syndrome - Chronic condition accompanied with weight loss	Judicious use of antibiotics, use of probiotics	Vancomycin and metronidazole are effective. Refer to specialist. Consider withdrawal of the suspect drug.
Gynaecomastia	Clinical symptoms and biopsy	Rare: INH, RIF Ethionamide	Lipomas, dermoid cysts, sebaceous cysts, ductal ectasia, hematomas, and fat necrosis FNAC will provide diagnosis	Resolves after stopping anti-TB drugs	Reassure patient and in severe cases, withdraw suspects drug.
Pellagra-like syndrome	Based on clinical symptoms of Dementia, Dermatitis and Diarrhea	Rare: INH Ethionamide	Chronic alcoholism - Malnutrition Amino acid imbalance - Hypoalbuminemia	Supplementation with nicotinamide and pyridoxine	Check for compliance. Increase the dose of nicotinamide and pyridoxine if required.
QT prolongation Torsade de pointes Arrhythmia	QTc ≥ 501 ms on at least two separate ECGs and /or arrhythmia on ECG	Rare: FQs Moxifloxacin Clofazimine Linezolid Clarithromycin	Hypokalemia, Metabolic acidosis, Atrial fibrillation, atrial flutter, ventricular arrhythmia, Paroxysmal supraventricular tachycardia	ECG of patients on FQs as and when indicated	Refer to specialist for management

Pancreatitis, Peptic ulcer, Depression, Encephalopathy, Pneumonitis, Myopathy, Rhabdomyolysis, Congestive cardiac failure, Pericarditis have also been reported rarely with anti-TB drugs.

Peripheral neuropathy, anemia, thrombocytopenia and optic neuritis with Linezolid (2nd line drugs) can be severe and need immediate referral to specialist.

Frequent: Seen in 1-10% patients

Rare: Seen in less than 1% patients

Laboratory test for TB patients

Timepoints	Laboratory tests
Baseline (Before initiating treatment if indicated)	LFT (ALT, AST, Serum bilirubin) RFT (Serum creatinine, Blood Urea, Urine routine and microscopy) Complete blood count, peripheral smear and Fib Blood glucose: Fasting and post-prandial (Random in non-diabetics) Total serum proteins, Albumin and Globulin Serum uric acid Serum electrolytes Thyroid function tests (T3, T4 and TSH) Ophthalmologic examination Psychiatric consultation (before starting Cycloserine) In females: Urine pregnancy test and USG of abdomen and pelvis
After 1.5 months	Ophthalmologic examination (for patients taking Ethambutol), if indicated
After 2 months of treatment as indicated	Tests mentioned at the baseline will be repeated Ophthalmologic examination: If EMB is stopped at or before 2 months, not required. If EMB is continued and ophthalmologic examination was not performed at 1.5 months, then it should be done.

Tests to be performed at 2 months will be repeated at 4 and 6 months if indicated.

Warning Symptoms for some serious adverse reactions

Warning Symptoms	For Medical officer/ General practitioner (GP): When to refer the patient
Rash Skin lesions on oral cavity, nose	If mucous membranes are involved OR rash is more than 10% of body surface area without mucous membrane involvement OR associated with fever and generalised swelling (edema); refer to specialist/tertiary care center immediately.
Pain in eye/s, Blurring of vision and Disturbance in color vision	Indicates Eye toxicity Refer the patient to specialist for evaluation
Loss of hearing/ Diminished hearing, Ringing in the ears, Dizziness and Loss of balance	Indicates Ear toxicity Refer the patient to specialist for evaluation.
Puffiness of face, Swelling over feet and Oliguria Anuria	Indicates Kidney toxicity. Treat the symptoms and refer the patient to specialist for evaluation.
Hallucinations, Seeing abnormal things and Suicidal or abnormal thoughts or actions	Indicates Psychiatric disturbances. Refer the patient to specialist for evaluation.

Absolute contraindications of anti-TB drugs: (Benefit - Risk have to be carefully assessed)

Drug	Absolute contraindications	Reason
Rifampicin	With Saquinavir and Ritonavir	Potential for hepatotoxicity is increased. Rifampicin is CYP3A4 inducer and can decrease Saquinavir level and effect
Ethambutol	Optic neuritis	Ethambutol can cause optic neuritis
Pyrazinamide	Acute porphyria Gouty arthritis Hepatic diseases	Pyrazinamide can precipitate acute porphyria Can inhibit excretion of urates Can cause drug induced hepatitis
Neomycin Kanamycin, Tobramycin, Amikacin, Capreomycin, Streptomycin	Concurrent use of two aminoglycosides With potent diuretics e.g. Furosemide Soon after use of anesthetics and muscle relaxants	Can potentiate nephrotoxicity Can potentiate otoandcity Can result in respiratory paralysis
Levofloxacin, Ofloxacin, Moxifloxacin	History of tendon disorders	Associated with risk of tendinitis and tendon rupture
Ethionamide	Severe hepatic impairment	Risk of worsening
Cycloserine	Epilepsy, Psychiatric illness - Depression, Severe anxiety, Psychosis , Severe renal insufficiency	Can precipitate seizures Can lead to severe psychosis and depression Can lead to Cycloserine toxicity
Clarithromycin	With Pimozide, Astemizole With Lovastatin or Simvastatin Hypokalemia and in patients with prolonged QT interval	Risk of QT prolongation Can cause rhabdomyolysis Risk of further QT prolongation
Imipenem	With Valproic acid and Probenecid	Decrease in valproic acid concentration and Increase in plasma levels of imipenem
Linezolid	With Monoamine oxidases A or B inhibitors (e.g. phenelzine, isocarboxazid, selegiline, moclobemide) within two weeks	Risk of MAO inhibition leading to serotonin syndrome

Algorithm for reintroduction of anti-TB drugs -To be done by experts only

Adverse drug reaction	Advice on reintroduction
Hepatotoxicity	Reintroduction after liver enzyme returns to ≤ 2 X ULN
Ocular toxicity	Main suspect drug is EMB Reintroduction of Ethambutol is not recommended
Immune mediated Nephritis	Main suspect drag is RIF Reintroduction with RIF is not recommended
Non serious cutaneous ADRs - no mucous membrane involvement or less than 10 Ye of BSA.	After withholding all drugs reintroduce one drug at a time
Serious Cutaneous adverse drug reactions - mucous membrane imrolvement or more than 10 'Vs of BSA.	Reintroduction is not recommended (applies for all anti-TB drugs).
Immune thrombocytopenia	Main suspect drug is RIF Reintroduction with RIF is not recommended
Gynecomastia	Symptoms takes long time to resolve (4-12 month) hence usually reintroduction is not required
Aplastic Anemia	Main suspect drug is INH Reintroduction with INH is not recommended
Nephrotoxiicity	Main suspect drags are AGs. AGs can be reintroduced at low doses after the renal function returns to normal
Ototoxicity	Main suspect drugs are AGs. Reintroduction of AGs is not recommended.
Cardiac arrhythmias including Torse de pointes (TdP)	Main suspect drugs are FQs. Reintroduction with FQs is not recommended.
Diarrhea	Reintroduction is recommended with one drug at a time every fourth day, once diarrhea is resolved
Seizures	Main suspect drugs are FQs. Reintroduction with FQs is not recommended.
Psychosis	Main suspect drugs is cycloserine. Reintroduction with cycloserine can be done at low dose but if symptoms recur than completely discontinue the drug.

Stepwise increase in the dosage for Reintroduction

1. Reintroduction of anti-TB drugs:

Drug	Day1	Day2	Day3
Isoniazid	50mg	Full dose	Full dose
Rifampicin	75mg	300mg	Full dose
Pyrazinamide	250mg	1000mg	Full dose
Ethionamide/Prothionamide	125mg	250mg	Full dose
Fluoroquinolones	50mg	200mg-250mg	Full dose
Cyclosporine	125mg	250mg	Full dose
Ethambutol	100mg	500mg	Full dose
PAS	1g	4g	Full dose
Capreomycin	125mg	500mg	Full dose
Kanamycin	125mg	500mg	Full dose
Amikacin	125mg	500mg	Full dose

If the test dose of any drug causes a reaction discontinue this drug, unless it is deemed essential to the regimen. If that is the case, desensitization can be considered.

2.Reintroduction of the drugs should be in hospitalized patients.

3. In patients with severe rash, dose increment should be slower than stated above.

4.For key drugs, Isoniazid, Rifampicin, Ethambutol, detailed desensitization protocol with very small dose and method of dosage preparation is available on the website - (http://www.who.int/topics/tuberculosis/en/)

Anti-TB drugs in pregnant & lactating women

Pregnancy

All female patients in reproductive age-group should be tested for pregnancy during initial evaluation
Generally pregnancy should be avoided in TB patients
Aminoglycosides (streptomycin, kanamycin, amikacin) are contraindicated through pregnancy
Ethionamide is contraindicated in first trimester of pregnancy
Mother's malnutrition may affect the development of the foetus
Continuation of pregnancy should be done in consultation with gynecologist / obstetrician
Pregnant patients need to be monitored carefully both in relation to treatment and progress of the pregnancy

Lactation

Breast feeding should not be discouraged. The mother should be advised about cough hygiene measures such as covering the nose and mouth while breast feeding, coughing, sneezing or any act which can produce sputum droplets. Most of the anti-TB drugs cross into breast milk at low levels. However the doses of drugs that babies receive via breast milk are insufficient to treat or prevent TB in the infant. Mothers receiving INH and their breastfed infants should be supplemented with vitamin B6 (pyridoxine), recommended dose of Pyridoxine in infants is 5 mg/day

Contraception

Rifampicin decreases the efficacy of oral contraceptives by increasing their metabolism so the use of Oral Contraceptive Pill (OCP) is not recommended during TB treatment. As per the patient's choice and availability, one of the following methods are recommended:

Double barrier method of contraception i.e. condom with spermicide (foam, gel, cream, or suppository), diaphragm (including occlusive cap or cervical/vault) with spermicide
IUD
Medroxyprogesterone acetate
High dose estrogen OCP

Anti-TB drugs in renally impaired patients

Dose modification for anti-TB drugs: Severity of renal impairment is defined by creatinine clearance (CrCl) and renal impairment is considered as: mild (1.5-2 mg/dL serum creatinine), moderate (2-3 mg/dL serum creatinine) and severe (> 3 mg/dL serum creatinine).

Estimated creatinine clearance calculations:

Men: Weight (kg) X (140 - age) / 72 X serum creatinine (mg/di)

Women: 0.85 X Weight (kg) X (190 - age) / 72 X serum creatinine (mg/d1))

Drug	Recommended dose and frequency for patients with CrCI < 30 ml/min or for patients receiving haemodialysis	Drug	Recommended dose and frequency for patients with CrCI < 30 ml/min or for patients receiving haemodialysis
Isoniazid	No adjustment necessary	Gatifloxacin	400 mg three times a week
Rifampicin	No adjustment necessary	Cycloserine	250 mg once daily, or 500 mg / dose three times per week
Pyrazinamide	25-35 mg/kg per dose three times per week (not daily)	Prothionamide	No adjustment necessary
Ethambutol	15-25 mg/kg per dose three times per week (not daily)	Ethionamide	No adjustment necessary
Streptomycin	12-15 mg/kg per dose two or three times per week (not daily)	PAS	4 g/dose, twice daily maximum dose
Capreomycm	12-15 mg/kg per dose two or three times per week (not daily)	Linezolid	No adjustment necessary
Kanamycin	12-15 mg/kg per dose two or three times per week (not daily)	Clofazimine	No adjustment necessary
Amikacin	12-15 mg/kg per dose two or three times per week (not daily)	Ammoxicillin/clavulanate	For 10-30 ml/min dose 1000 mg as amoxicillin component BD; For CrCI <10 ml/min dose 1000 mg as amoxicillin component OD
Ofloxacin	600-800 mg per dose three times per week (not daily )	Imipenem / cilastin	For CrCl 20-40 ml/min dose 500 mg every 8 hours; For CrCI <20 ml/min dose 500 mg every 12 hr
Levofloxacin	750-1000 mg per dose three times per week (not daily)	Meropenem	For CrCI 20-40 ml/ min dose 750 mg every 12hr; For CrCI <20 ml/min dose 500 mg every 12 hr
Moxifloxacin	No adjustment necessary	High dose isoniazid	Recommendations not available

Commonly used ancillary medicines

Management of adverse reaction often requires use of ancillary medicines to reduce or lessen side effects. Below is list of indications and commonly used medicines for management of adverse reactions.

Indication	Drugs
Nausea, vaunting, Stomach upset	Domeperidone, metoclopramide, prochlorperazine, promethazine, ondansetron
Heartburn, indigestion and acidity	H2-blockers (ranitidine etc.), proton pump inhibitors (omeprazole, pantoprazole etc) Antacid syrups and the antacids if prescribed should be taken at least 2 hours apart from anti-TB drugs
Oral candidiasis	Fluconazole, clotrimazole lozenges, nystatin suspension
Diarrhoea	ORS sachets
Prophylaxis of peripheral neuropathy of cycloserine and isoniazid	Pyridoxine (vitamin B6)
Musculoskeletal pain, Arthralgia, headaches	Give paracetamol / ibuprofen / aspirin / diclofenac. If caused by fluoroquinolones, refer to specialist immediarely. Tendonitis can progress to tendon rupture.
Cutaneous reactions, itching	Hydrocortisone cream, calamine lotion
Systemic hypersensitivity Reactions	Antihistamines (diphenhydramine, chlorpheniramine, dimenhydrinate) Systemic corticosteroids (prednisone, prednisolone, Dexamethasone) are reserved only for very severe reactions
Bronchospasm	Inhaled beta-agonists (salbutamol, albuterol, etc.), inhaled corticosteroids (beclomethasone, etc.)
Hypothyroidism	Levothyroxine
Electrolyte wasting	Potassium and magnesium replacement therapy (oral formulations)

Source: ICMR book on Prevention and management of adverse reactions associated with Anti TB drugs

শেহতীয়া উন্নীতকৰণ: : 2/12/2020

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