Transcript rifampicin
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It is provided to you by the ERS for your personal use only, as submitted by the author. 2012 by the author Management of adverse drug events Graham Bothamley Homerton University Hospital NHS Foundation Trust, London; UK Elmira Ibrahim Marius Nasta Institute, National Tuberculosis Program Bucharest; Romania Christoph Lange Clinical Infectious Diseases, Research Center Borstel University of Lübeck; Germany Definitions - I Adverse drug reaction A response to a medicine which is noxious and unintended, and which occurs at doses normally used in man Adverse drug event Any untoward medical occurrence that may present during treatment with a pharmaceutical product, but which does not necessarily have a causal relationship with this treatment Causal The medicine has contributed to or caused the event Causality assessment The evaluation of the likelihood that a medicine was the causative agent of an observed adverse reaction Dechallenge The withdrawal of a drug from a patient; the point at which the continuity, reduction or disappearance of adverse effects may be observed Rechallenge The voluntary or inadvertent re-administration of a medicine suspected of causing an adverse reaction. The point at which a drug is again given to a patient after its previous withdrawal Definitions - II Relationship assessment The objective evaluation of the relationship between the administration of a medicine and a health event, taking into consideration duration of therapy to onset of event, response to dechallenge and rechallenge (if performed) and the presence of other diseases or medicines that could have caused the event. This process stops short of attempting to establish a causal relationship, but is an essential preliminary. Risk factor A characteristic associated with an increased probability of occurrence of an event. In the presence of a risk factor, a patient is more likely to develop an adverse reaction. Serious Reaction A serious reaction is an adverse drug reaction which involves any of the following: - death or a life-threatening experience; - hospitalization or prolongation of hospitalization; - persistent significant disability; - congenital anomaly Major Clinical Categories in Events Dictionary • • • • • • • • • • • • Accidents Alimentary Associations (of concomitant medicines & events) Autonomic Circulatory Died Device Endocrine / metabolic Ear, Nose & Throat Eyes Haematological Hepatobiliary • • • • • • • • • • • • • • • Immunological Infections Lactation exposure Musculoskeletal Neoplasms Neurological Poisoning Pregnancy register Mental health disorders Reproductive organs Respiratory Skin Surgery Unclassified Urological Individual medicines for TB therapy (alphabetical) Am amikacin Lfx levofloxacin Amx/Clv amoxicillin/clavulanate Lzd linezolid Cm capreomycin Mfx moxifloxacin Cfx ciprofloxacin Ofx ofloxacin Clr clarithromycin PAS p-aminosalicylic acid Cfz clofazimine Pto protionamide Cs cycloserine Z pyrazinamide E ethambutol Rfb rifabutin Eto ethionamide R rifampicin Gfx gatifloxacin S streptomycin Ipm imipenem Trd terizidone H isoniazid Thz thioacetazone Km kanamycin Antituberculosis drugs (by group) Group Description Drug Abbreviation 1. First-line oral antituberculosis drugs isoniazid rifampicin ethambutol pyrazinamide rifabutin H R E Z Rfb 2. Injectable antituberculosis drugs kanamycin amikacin capreomycin streptomycin Km Amk Cm S 3. Fluoroquinolones levofloxacin moxifloxacin ofloxacin Lfx Mfx Ofx 4. Oral bacteriostatic second-line antituberculosis drugs ethionamide protionamide cycloserine terizidone p-aminosalicylic acid Eto Pto Cs Trd PAS 5. Antituberculosis drugs with unclear efficacy or unclear role in MDR-TB treatment (not recommended by WHO for routine use in MDR-TB patients) clofazimine linezolid amoxicillin/clavulanate thioacetazone clarithromycin imipenem Cfz Lzd Amx/Clv Thz Clr Ipm ADRs commonly associated with anti-TB drugs First-line drugs* Second-line drugs** Hepatitis Nausea/vomiting Nausea/vomiting/GI upset Diarrhoea Rash Arthralgia Weakness/fatigue Dizziness/vertigo Arthralgia Hearing disturbances Fever Headache Pruritus Sleep disturbances Headache Electrolyte disturbances Vertigo/tinnitus Abdominal pain Visual disturbances Anorexia Paraesthesia Gastritis Anorexia/weight loss Peripheral neuropathy Abdominal pain Depression Swelling Tinnitus Palpitations Allergic reaction Dyspnoea Rash Seizures Visual disturbances Neutrophilia Seizures Hypothyroidism Psychosis Hepatitis Renal failure/nephrotoxicity Potentially overlapping toxicities of antiretrovirals and antituberculosis agents Potential toxicity Antiretroviral therapy Anti-tuberculosis therapy Peripheral neuropathy stavudine didanosine cycloserine isoniazid ethambutol fluoroquinolones streptomycin kanamycin amikacin capreomycin viomycin ethionamide/prothionamide linezolid Psychiatric symptoms efavirenz cycloserine isoniazid fluoroquinolones ethionamide/prothionamide Hepatitis nevirapine ritonavir-boosted protease inhibitors efavirenz etravirine maraviroc pyrazinamide isoniazid rifampicin/rifabutin p-aminosalicylic acid ethionamide/prothionamide fluoroquinolones Potential toxicity Antiretroviral therapy Anti-tuberculosis therapy Gastrointestinal intolerance zidovudine protease inhibitors didanosine ethionamide/prothionamide p-aminosalicylic acid pyrazinamide isoniazid rifampicin ethambutol clofazimine Renal toxicity tenofovir indinavir streptomycin kanamycin capreomycin amikacin viomycin rifampicin Bone marrow toxicity zidovudine linezolid rifampicin/rifabutin Lactic acidosis stavudine didanosine zidovudine linezolid Stevens–Johnson syndrome nevirapine efavirenz etravirine thioacetazone cycloserine linezolid ethambutol streptomycin Arrhythmias / QT prolongation atazanavir/ritonavir saquinavir/ritonavir lopinavir/ritonavir fluoroquinolones Rash / pruritus nevirapine efavirenz etravirine abacavir rifampicin/rifabutin pyrazinamide Grade of toxicity Grade Toxicity GRADE 1 Mild Transient or mild discomfort; no limitation in activity; no medical intervention or therapy required GRADE 2 Moderate Mild to moderate limitation in activity— some assistance may be needed; no or minimal medical intervention or therapy required GRADE 3 Severe Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalization possible GRADE 4 Lifethreatening Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable Adverse reaction Symptoms and signs Usual drug responsible Audiovestibular manifestations Hearing loss, vertigo, new-onset tinnitus Aminoglycosides, capreomycin Blood sugar abnormalities Dizziness, sweating, fainting, poor response to infections Fluorquinolones (FQ), rifampicin (R), pyrazinamide (Z) Dermatitis (2) Itching, rash, hives, fever, petechial rash Z, rifamycins; thiacetazone & HIV Gastro-intestinal (1) Anorexia, nausea, vomiting, epigastric pain Z, rifamycins; PAS Haematology Leucopenia, thrombocytopenia, anaemia, eosinophilia R (intermittent); linezolid, H, capreomycin Hepatitis (3) Anorexia, nausea, vomiting, jaundice, abdominal pain RHZ(E) Hypothyroidism Fatigue, weight gain, depression PAS, pro/etionamide Joint, tendon Gout-like manifestations; SLE; tendinopathies Z; H (rarely R); FQ; Neuro/psychiatric Headaches, depression, agitation; suicidal ideation H, FQ; cycloserine Peripheral neuropathy Numb feet or hands H, linezolid; cycloserine, aminoglycosides Renal impairment Uraemia; haematuria Aminoglycosides, capreomycin; rifampicin (intermittent) Visual Vision loss and colour blindness; uveitis E, linezolid; rifabutin, rifapentane; Major adverse reactions Adverse reaction Probable cause Action Skin rash with or without itching Streptomycin, isoniazid, rifampicin, pyrazinamide Stop anti-TB drugs Deafness (no wax on otoscopy) Streptomycin Stop streptomycin Dizziness (vertigo and nystagmus) Streptomycin Stop streptomycin Jaundice (other causes excluded), hepatitis Isoniazid, pyrazinamide, rifampicin Stop anti-TB drugs Confusion (suspect druginduced acute liver failure if there is jaundice) Most anti-TB drugs Stop anti-TB drugs Visual impairment (other causes Ethambutol excluded) Stop ethambutol Shock, purpura, acute renal failure Rifampicin Stop rifampicin Decreased urine output Streptomycin Stop streptomycin Minor adverse reactions Adverse reaction Nausea, anorexia Probable cause Action RHZ Anti-emetic; with a small meal Joint pains Z NSAIDs (vitamin D?) Drowsiness H Take at bed-time Itching R Anti-histamine Drug interactions Alcohol Anticoagulation Opiates Oral contraceptive RHZ R R R Avoid or limit intake Daily heparin (danger if double dose of warfarin) Double dose Alternative contraception Cessation of a single drug Adverse event Drug to stop Deafness Vertigo and nystagmus Renal impairment Streptomycin Visual impairment (exclude other causes) Ethambutol Flu like syndrome with shock purpura acute renal impairment Rifampicin Management of cutaneous reactions • Itching without a rash and there is no other obvious cause - symptomatic treatment with antihistamines and skin moisturizing, - continue TB treatment while observing the patient closely. • If a skin rash develops - all anti-TB drugs must be stopped. - Once the reaction has resolved, anti-TB drugs are reintroduced one by one, starting with the drug least likely to be responsible for the reaction (rifampicin or isoniazid) at a small challenge dose, such as 50 mg isoniazid. - The dose is gradually increased over 3 days. - This procedure is repeated, adding in one drug at a time. A reaction after adding in a particular drug identifies that drug as the one responsible for the reaction ! - The alternative regimens are applicable when a particular drug cannot be used because it was implicated as the cause of a cutaneous reaction. Drug-induced hepatitis Diagnosis • AST/ALT > 3-5x upper limit of normal • Rise in bilirubin above normal Action • Stop RHZ • If treatment required SEFq Re-introduction of TB drugs (1) • LFTs normal or AST/ALT <2x upper limit • If LFTs due to EtOH (or not due to TB drugs) – restart RHZ together • If bilirubin and ALP – rifampicin most likely – start HE – add Z 1 week later if OK – If OK, use S (+Fq) Re-introduction of TB drugs (2) • ATS : R RH RHE (2RHE/7RH) • Common: H RH RHE (2RHE/7RH) • NYBTC: E ER REZ (2REZ/7RE) » If R the problem, 2SHEZ/10HE » If H the problem, 2REZ/7RE » If Z the problem, 2SHE(Fq)/10HE Second line drugs • Minor adverse effects – treat symptomatically • Major adverse effects – stop drug if possible (except hypothyroidism PAS, Eto/Pto) – drug treatment of symptoms if essential » anticonvulsants » amitriptyline or gabapentin for peripheral neuropathy » amiloride or spironolactone if K+ or Mg2+ » antipsychotics (may be effective treatment!) » avoid PPIs (pyrazinamide) » avoid aspirin NSAIDs (efflux) Monitoring and recording adverse effects Most TB patients complete their treatment without any significant adverse drug effects. However, a few patients do experience adverse effects. Important that patients be clinically monitored during treatment so that adverse effects can be detected promptly and managed properly. Routine laboratory monitoring is not necessary. Method: - teaching patients how to recognize the symptoms of common effects, - urging them to report if they develop such symptoms - asking about symptoms when patients come to collect drugs. Adverse reactions to drugs should be recorded on the TB Treatment Card under “Observations”. Clinical review of symptoms and signs, medication use, side-effects, complications Ask If this is first visit: • Review the patient’s past medical history, including their past history of TB treatments. For all visits: • How have you been? • Have you needed urgent medical care? If yes, ask for record/diagnosis. • Have your TB symptoms improved? – Cough? Sputum? – Difficult breathing? – Fever/night sweats? – Weight loss? • Have you had any side-effects? – Nausea/vomiting? – Fatigue? – Skin rash? – Tingling in hands or feet? – Deafness? Ringing of ears? – Headache? – Seizures? Loss of consciousness? – Feeling anxious? Feeling sad or unhappy? • What problems have you had taking the medicines? • Have you missed any doses? • Have you had any problems with your treatment supporter? • What else do you want to talk about? Look In all patients: • Weigh the patient. Calculate weight gain or loss. Record. If weight loss, ask about food intake • Measure temperature • Count respiratory rate • Look for pallor. If pallor, check haemoglobin • Look at whites of the eye—yellow? • Look for thrush If any new symptoms: • Do further assessment of symptoms. Monitoring during treatment of DR-TB Monitoring evaluation Recommended frequency Evaluation by clinician At baseline, and at least monthly until conversion, then every 2–3 months Screening by DOT worker At every DOT encounter Sputum smears and cultures Monitor smears and cultures monthly throughout treatment. (Note: programmes with limited resources may choose to do smears monthly but cultures only every other month) Weight At baseline and then monthly Drug susceptibility At baseline in programmes doing individualized treatment Chest radiograph At baseline, and then every 6 months Serum creatinine At baseline, then monthly if possible while receiving an injectable drug. Every 1–3 weeks in HIV-infected patients, diabetics and other high-risk patients Serum potassium Monthly while receiving an injectable agent. Every 1–3 weeks in HIV-infected patients, diabetics and other high-risk patients Monitoring evaluation Recommended frequency Thyroid stimulating hormone (TSH) Every 6 months if receiving ethionamide/protionamide hormone and/or PAS; and monitor monthly for signs/symptoms of hypothyroidism. TSH is sufficient for screening for hypothyroidism; it is not necessary to measure hormone thyroid levels Liver serum enzymes Periodic monitoring (every 1–3 months) in patients receiving pyrazinamide for extended periods or for patients at risk for or with symptoms of hepatitis. For HIV-infected patients, do monthly monitoring HIV screening At baseline, and repeat if clinically indicated Pregnancy tests At baseline for women of childbearing age, and repeat if indicated Haemoglobin and white blood count If on linezolid, monitor weekly at first, then monthly or as needed based on symptoms; there is little clinical experience with prolonged use For HIV-positive patients on an ART regimen that includes AZT, monitor monthly initially and then as needed based on symptoms Lipase Indicated for work up of abdominal pain to rule out pancreatitis in patients on linezolid, D4T, ddI, ddc. Lactic acidosis Indicated for work up of lactic acidosis in patients on linezolid or ART Serum glucose If receiving gatifloxacin, monitor glucose frequently (weekly) and educate patient on signs and symptoms of hypoglycaemia and hyperglcycaemia Prevention of adverse effects of drugs Some drug-induced side-effects can be prevented! Eg: isoniazid / cycloserine / terizidone - induce peripheral neuropathy: numbness or a tingling or burning sensation of the hands or feet Occurs more commonly in: - pregnant women - people with the following conditions: HIV infection, alcohol dependency, malnutrition, diabetes, chronic liver disease, renal failure. These patients should receive preventive treatment with pyridoxine, 10 mg/day along with their anti-TB drugs (other guidelines recommend 25 mg/day) Commonly used ancillary medications Indication Drug Nausea, vomiting, upset stomach Metoclopramide, dimenhydrinate, prochlorperazine, promethazine, bismuth subsalicylate Heartburn, acid indigestion, sour stomach, ulcer H2-blockers (ranitidine, cimetidine, famotidine, etc.), proton pump inhibitors (omeprazole, lansoprazole, etc.) Avoid antacids because they can decrease absorption of flouroquinolones Oral candidiasis (non-AIDS patient) Fluconazole, clotrimazole lozenges Diarrhoea Loperamide Depression Selective serotonin reuptake inhibitors (fluoxetine, sertraline), tricyclic antidepressants (amitriptyline) Severe anxiety Lorazepam, diazepam, clonazepam Insomnia Dimenhydrinate Psychosis Haloperidol, thorazine, risperidone (consider benzotropine or biperiden to prevent extrapyramidal effects) Indication Drug Seizures Phenytoin, carbamazepine, valproic acid, phenobarbital Prophylaxis of neurological complications of cycloserine Pyridoxine (vitamin B6) Peripheral neuropathy Amitriptyline Vestibular symptoms Meclizine, dimenhydrinate, prochlorperazine, promethazine Musculoskeletal pain, arthralgia, headaches Ibuprofen, paracetamol, codeine Cutaneous reactions, itching Hydrocortisone cream, calamine, caladryl lotions Systemic hypersensitivity reactions Antihistamines (diphenhydramine, chlorpheniramine, dimenhydrinate), corticosteroids (prednisone, dexamethasone) Bronchospasm Inhaled beta-agonists (albuterol, etc.), inhaled corticosteroids (beclomethasone, etc.), oral steroids (prednisone), injectable steroids (dexamethasone, methylprednisolone) Hypothyroidism Levothyroxine Electrolyte wasting Potassium and magnesium replacement