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Les médicaments pour traiter la tuberculose Cheleste M. Thorpe MD Tufts Medical Center, Boston, MA USA November 2011
Antituberculeux de première ligne ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Tous les médicaments de première ligne TB ont un important potentiel d'effets indésirables.
Médicaments antituberculeux de Deuxième ligne ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
La plupart des médicaments de la deuxième ligne TB ont un potentiel d’encore plus d'effets indésirables que les médicaments de première ligne TB. Aussi, ils sont plus difficiles à prendre, et/ou moins efficaces, que les médicaments de la première ligne .
Objectifs pour cette session ,[object Object],[object Object]
Les effets indésirables peuvent produire des grosses problèmes ,[object Object],[object Object],[object Object],[object Object],[object Object]
Facteurs de risque de développer une RMA ,[object Object],[object Object],[object Object],[object Object],[object Object]
Isoniazid ,[object Object],[object Object],[object Object]
Isoniazid, continued ,[object Object],[object Object]
Isoniazid, continued ,[object Object]
Case ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Case ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Rifampin ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Sérieux interactions médicamenteuses se produisent avec RIF et peut être contre-indiqués ,[object Object],[object Object],TOUJOURS VERIFIER CHAQUE MED INTERACTION AVEC RIF!
Rifampin, continued ,[object Object],[object Object],[object Object]
Pourquoi utiliser Rifamycines si elles ont tellement de potentiel pour les interactions médicamenteuses? ,[object Object]
Case ,[object Object],[object Object],[object Object]
RIF est contre-indiqué avec certains médicaments ,[object Object]
La rifabutine peut remplacer RIF lorsque d'autres médicaments métabolisés par P450 sont prises
Rifabutin (RFB) ,[object Object]
Rifabutin (RFB) ,[object Object]
Quelles sont les interactions médicamenteuses entre les PI et le RFB? ,[object Object],[object Object]
Rifapentine (RPT) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Pyrazinamide (PZA) ,[object Object],[object Object],[object Object],[object Object]
Case ,[object Object],[object Object],[object Object],[object Object]
Ethambutol (EMB) ,[object Object],[object Object],[object Object],[object Object]
Qu'est-ce qui se passe ici? ,[object Object],[object Object],[object Object]
Qui développe la neuropathie optique sur l'EMB? ,[object Object],[object Object],[object Object]
Contrôlez le risque de l'EMB-induite névrite optique ,[object Object],[object Object],*http://clinicaltrials.gov/ct2/show/NCT01048697- L'hypothèse que les individus obèses auront besoin d'une dose> corporel idéal de poids les résultats de l'étude ne sont pas rapporté cependant.
Contrôlez le risque de l'EMB-induite névrite optique ,[object Object],[object Object]
Contrôlez le risque de l'EMB-induite névrite optique ,[object Object],[object Object]
Thérapie de deuxième ligne ,[object Object],[object Object],[object Object],[object Object]
éducation du patient ,[object Object]
Case ,[object Object],[object Object],[object Object]
Effets secondaires des médicaments peuvent être importants, même s'ils ne sont pas "sérieux"
Questions à poser ,[object Object],[object Object]
Questions Cont’d ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
observation des patients ,[object Object],[object Object],[object Object],[object Object]
Surveillance des effets indésirables ,[object Object]

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Medications To Treat Tuberculosis Symposia - The CRUDEM Foundation

  • 1. Les médicaments pour traiter la tuberculose Cheleste M. Thorpe MD Tufts Medical Center, Boston, MA USA November 2011
  • 2.
  • 3. Tous les médicaments de première ligne TB ont un important potentiel d'effets indésirables.
  • 4.
  • 5. La plupart des médicaments de la deuxième ligne TB ont un potentiel d’encore plus d'effets indésirables que les médicaments de première ligne TB. Aussi, ils sont plus difficiles à prendre, et/ou moins efficaces, que les médicaments de la première ligne .
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17.
  • 18.
  • 19.
  • 20. La rifabutine peut remplacer RIF lorsque d'autres médicaments métabolisés par P450 sont prises
  • 21.
  • 22.
  • 23.
  • 24.
  • 25.
  • 26.
  • 27.
  • 28.
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34.
  • 35.
  • 36. Effets secondaires des médicaments peuvent être importants, même s'ils ne sont pas "sérieux"
  • 37.
  • 38.
  • 39.
  • 40.

Notes de l'éditeur

  1. Medications to treat Tuberculosis
  2. First line TB drugs
  3. All of the first line TB drugs have significant potential for adverse effects.
  4. Second line TB drugs
  5. Most of the second line TB drugs have even greater potential for adverse effects than the first line TB drugs, and/or are more difficult to take, or less effective .
  6. Objectives for this session To become familiar with some of the common adverse reactions to first-line TB medications, and recognize them in clinical scenarios. To be aware of some of the adverse reactions to second-line TB medications.
  7. Adverse drug reactions can lead to big problems May decrease patient’s quality of life May prevent optimal drug use in some patients May necessitate supportive care May significantly complicate treatment May result in temporary or permanent harm, disability, or death
  8. Risk Factors for Developing an ADR Multiple drug therapy Number of drugs being taken Over the counter medications Alcohol Drugs of abuse Age Very young Very old Pregnancy Risk to fetal development (usually first trimester) Co-morbidity/chronic diseases – can alter a drug’s absorption, distribution, metabolism or elimination Hereditary factors
  9. Bactericidal Spectrum is mainly M. tuberculosis Adverse effects: Asymptomatic hepatic enzyme elevation Hepatitis Peripheral neuropathy CNS effects (rare at conventional dosing) SLE-like symptoms Hypersensitivity reaction Monoamine (Histamine/tyramine poisoning) Diarrhea
  10. Drug Interaction Phenytoin Monitoring Routine monitoring is not necessary Liver function tests should be done before starting INH treatment and every month during therapy: People living with HIV People with history of liver disease People who use alcohol regularly Women who are pregnant or just had a baby People taking medications that may increase risk of hepatitis
  11. Prevention Vitamin B6 may prevent peripheral neuropathy and CNS effects
  12. A 24 year old HIV-negative man presents with pulmonary TB. He takes no other medications, but drinks more than 12 units of alcohol on the weekends. You begin RIPE. Which of the following is FALSE? He should have LFTs done prior to initiation of therapy. Since he only drinks on the weekends and is young, he does not need monitoring of liver function. He should have directly observed therapy. If he develops anorexia, nausea, or abdominal pain, he should be evaluated as soon as possible, and TB medications should be held.
  13. A 24 year old HIV-negative man presents with pulmonary TB. He takes no other medications, but drinks more than 12 units of alcohol on the weekends. You begin RIPE. Which of the following is FALSE? He should have LFTs done prior to initiation of therapy. Since he only drinks on the weekends and is young, he does not need monitoring of liver function. He should have directly observed therapy. If he develops anorexia, nausea, or abdominal pain, he should be evaluated as soon as possible, and TB medications should be held.
  14. Bactericidal Spectrum M.tb, but other uses as well Adverse Effects: Cutaneous reactions Gastrointestinal reactions Flu-like syndrome Hepatotoxicity Severe immunologic reactions Orange discoloration of bodily fluids
  15. Serious drug-drug interactions occur with RIF, and RIF may be contraindicated DRUGS that interact with RIF HIV meds Other antibiotics Hormone therapy Narcotics Anticoagulants Immunosuppressive agents Anticonvulsants Cardiovascular agents Bronchodilators Sulfonylurea hypoglycemics Hypolipidemics Psychotropic drugs
  16. Monitoring No routine monitoring required When given with drugs that interact, may necessitate regular measurements of the serum concentrations of the drugs in question
  17. Why use Rifamycins if they have so much potential for drug-drug interactions? In randomized trials, regimens without rifampin or in which rifampin was only used for the first two months of therapy resulted in higher rates of tuberculosis treatment failure and relapse
  18. An HIV-positive patient is resistant to the NNRTI’s, and is taking a PI-based antiretroviral therapy. He has pulmonary TB, and needs to start treatment. Why is Rifampin is contraindicated?
  19. Standard doses of protease inhibitors cannot be given with rifampin; the > 90% decreases in trough concentrations of the protease inhibitors will make them ineffective
  20. RFB can replace RIF when other P450-metabolized drugs are being taken
  21. Adverse effects: Hematologic toxicity Uveitis GI symptoms Polyarthralgia Hepatitis Rash Orange discoloration of bodily fluids
  22. Drug interactions and monitoring – see RIF cross-resistance with RIF less effect on LFTs less effect on cytochrome P450, so often used when RIF contraindicated due to drug-drug interactions
  23. What are the drug-drug interactions between PI’s and RFB? Little effect of rifabutin on PI concentrations but marked increases in rifabutin concentrations Need to dose-reduce rifabutin
  24. Adverse effects: Similar to those associated with RIF May increase metabolism of co-administered drugs that are metabolized by hepatic enzymes Drug Interactions: Are likely to be similar to those of RIF Monitoring: Similar to that for RIF
  25. Bacteriocidal Main use is for M. tb Adverse effects: Hepatotoxicity GI symptoms Non-gouty polyarthralgia Hyperuricemia Acute gouty arthritis Rash Monitoring Serum uric acid measurements are not routinely recommended Liver function tests should be performed when the drug is used in patients with underlying liver disease
  26. A 50 year old HIV negative man has been on RIPE for 2 months. He complains of anorexia, nausea, and fatigue, and is mildly jaundiced. Liver function tests are elevated. Which drug(s) are the most likely culprits? What do you do?
  27. Bacteriostatic/cidal at high doses Main use is to prevent emergence of resistance in TB therapy Adverse effect: Optic neuritis (impaired perception of the red and green colors) Cutaneous reactions Monitoring Baseline and monthly tests of visual acuity and color vision Educate patient about self monitoring their vision and reporting any visual changes to their physician immediately
  28. What’s happening here? 62-year old diabetic, hypertensive man Developed pulmonary TB Has been on treatment with 4 drugs for 2 months Begins complaining of blurry vision and difficulty distinguishing colors.
  29. Who develops optic neuropathy on EMB? Dose-related, but approximately 1% of patients on usual dose of 15-25 mg/kg. Risk increases with age (children rarely develop it, and WHO has recently changed recommendations in age <5). Patients with renal impairment (EMB is cleared by both glomerular filtration, and tubular secretion).
  30. Managing the risk of EMB-induced optic neuritis Verify that dose is correct, and adjust for renal function (and obesity*). Perform a pre-treatment opthalmologic exam to establish baseline. *http://clinicaltrials.gov/ct2/show/NCT01048697- Hypothesize that obese individuals will need a dose > ideal body weight—no study results reported yet.
  31. Managing the risk of EMB-induced optic neuritis Use caution in patients who cannot report on visual symptoms (example: mentally ill, non-verbal, or demented). WHO has recently changed EMB recommendations for children: now recommended for use in children of all ages including those of less than 5 years of age. Children require higher dosages than adults to achieve the same serum concentrations. Available data in HIV-uninfected children suggest that the revised dosages are within limits that have a very low risk of toxicity.
  32. Managing the risk of EMB-induced optic neuritis Educate patients about the possible symptoms (loss of visual acuity, color vision, and visual field). Make sure that patients know what to do if these symptoms occur.
  33. Second line therapy Cycloserine Psychosis, seizures Ethionamide and PAS GI upset Fluoroquinolones Tendon rupture Aminoglycosides Deafness Renal failure
  34. Patient Education Health care workers must clearly explain to patients the following: When the medication should be taken How much How often All patients should be educated about: TB Medication dosages Possible side effects Importance of taking the medication
  35. A 32 year old woman who was started on RIPE for TB 3 days ago comes to clinic. She says that she is worried, because her urine has turned bright orange. She has also noticed that her sheets are sometimes stained orange. She is afraid she isn’t going to get better, and wants to just stop her treatment altogether.
  36. Side effects of medications can be significant, even if they aren’t “serious”
  37. Questions To Ask How do you feel? Do you have any of the following: Abdominal pain Fatigue Unusual breathing Rash Joint pains/swellings Other unusual symptoms
  38. Questions Cont’d Are you taking any medications other than anti-TB medications? Prescription medications, herbal remedies or vitamins How is your appetite? How do you feel after you take the medications? Have you had any weight gain or loss? What color is your urine (should be orange for patients on rifampin)? Do you have any fever?
  39. Patient Observation Does the patient have signs and symptoms of hepatitis including any of the following: Yellow eyes Yellow skin Nausea or vomiting Abdominal pain or tenderness Does the patient have any rash? Is the patient gaining weight? Are you having any problems taking the anti-TB medications?
  40. Monitoring for Adverse Reactions Close monitoring of patients throughout treatment can: Prevent serious complications Promote continuity of care Improve patient-health care provider relationship Encourage adherence Ensure successful completion of treatment