33 Treatment of Tuberculosis Cupo Flashcards
What are the First-Line Antituberculosis Drugs used?
RIPE: Rifampin (RIF), Isoniazid (INH), Pyrizinamide (PZA), Ethambutol (EMB). Also Rifabutin, Rifapentin
What are the Second Line Antituberculosis Drugs used?
Streptomycin (SM), Cycloserine, p-Aminoslicylic acid, Ethionamide, Amikacin or Kanamycin, Capreomycin, Levofloxacin, Moxifloxacin, Gatifloxacin, Linezolid
How does Rifampin work?
Inhibits RNA synthesis
How does Isoniazid work?
Inhibits cell wall synthesis
How does Pyrazinamide work?
Exact target unclear. Disrupts plasma membrane. Disrupts energy metabolism
How does Ethambutol work?
Inhibits cell wall synthesis
What is the role of the new drug: Rifabutin (Mycobutin)?
Recommended when unacceptable drug interactions with Rifampin. Has a lower potential for CYP450 induction
What is the role of the new drug: Rifapentin (Priftin)?
Recommended for once-weekly continuation phase for HIV (-) adults w/ drug susceptible non-cavitary TB and (-) AFB smears at completion of initial phase smear
What is the general treatment regimen for TB like?
Always consider starting with 4 drug regimens (preferred: RIPE). Initial phase: 2 months. Continuation phase: 4 months (7 months for some patients)
What patients is the 7 month continuation therapy recommended?
1) Patients w/ cavitary pulmonary TB caused by drug susceptibility organisms and whose sputum culture obtained at the time of completion of initial phase is (+). 2) Patients whose initial phase did not include PZA. 3) Patients being treated w/ once weekly INH and rifapentine and whose sputum culture obtained at the time of completion of initial phase is (+)
What is the treatment of Culture-Positive TB (DAILY option)?
Initial Phase: 2 months RIPE daily (total of 56 doses within 8 weeks). Continuation phase: 1) 4 months: INH and RIF daily. 2) 4 months: INH and RIF twice/week. 3) 7 months: INH and RIF daily. 5) 7 months: INH and RIF twice/week
What is the treatment for Culture-Positive TB (Twice-weekly option)?
Initial Phase: 0.5 months: RIPE daily (total 10-14 doses w/in 2 weeks), 1.5 months: RIPE twice/week (12 doses w/in 6 weeks). Continuation Phase: 1) 4 months: INH and RIF twice/week (18 weeks), 2) 7 months: INH and RIF daily (twice/week for 31 weeks)
What is the treatment for Culture-Positive TB (Thrice-weekly option)?
Initial phase: 2 months (RIPE 3 times/week (8 weeks)). Continuation phase: 1) 4 months: INH and RIF 3x/week (18 weeks), 2) 7 months: INH and RIF 3x/week (31 weeks)
What are the recommended uses for the second-line drugs in TB?
When there is a drug intolerance, special population, drug resistance
What is the dosing of Isoniazid (INH) like for QD, 1x/week, 2x/week, 3x/week?
QD (5mg/kg: 300mg). 1-3x/week (15mg/kg: 900mg)
What is the dosing of Rifampin (RIF) like for QD, 1x/week, 2x/week, 3x/week?
Same for all of them: 10mg/kg (600mg)
How is Pyrazinamide (PZA) dosed?
20-25mg/kg/day. Weight: 40-55 (QD: 1,000mg, 2x weekly: 1,500mg, 3x weekly: 2,000mg). Other weight categores are 56-75 and 76-90
How is Ethambutol (EMB) dosed?
15-20mg/kg/day. Weight 40-55kg (QD: 800mg, 2x weekly: 1,200mg, 3x weekly: 2,000mg)
What are the formulations that Isoniazid come in?
Tablets (50, 100, 300mg). Elixer (50mg/5ml). Aqueous solution (100mg/ml) for IV or IM
What are the formulations that Rifampin come in?
Capsule (150, 300mg). Powder for oral administration. Aqueous solution for injection
What are the formulations that Pyrazinamide come in?
Tablet (500mg, scored)
What are the formulations that Ethambutol come in?
Tablet (100, 400mg)
Which first line agents have high CSF concentrations?
INH (90-100%). PZA (~80%)
Which first line agent is primarily renally cleared?
EMB. All others mainly hepatic
Which first line agent doesn’t need renal adjustment?
INH. RIF
Which first line agent doesn’t need hepatic adjustment?
EMB
Which first line agent DOES need renal adjustment?
Pyrazinamide. Ethambutol
What are some notable ADRs associated with INH?
Increase ALT/AST
What are some notable ADRs associated with RIF?
Orange discolor of body fluids: may permanently stain contact lenses and clothing
What are some notable ADRs associated with PZA?
Increased uricemia. Non-gouty polyarthralgia. Photosensitivity
Which first line agents can cause hepatic failure?
INH: hepatitis (rare) increased w/ RIF combo. PZA: severe/fatal w/ RIF combo
Which first line agents can cause neuropathy?
INH. EMB
What are some rare/severe ADRs with INH?
Lupus-like syndrome. Monoamine/tyramine poisoning
What are some rare/severe ADRs with RIF?
Flu-like symptoms. Immunologic reactions
What are some rare/severe ADRs with PZA?
Acute gouty arthritis
What are some rare/severe ADRs with EMB?
Optic neuritis
What are some patient counseling points for Rifampin?
Take w/ full glass of water on empty stomach (1 hr before or 2 hrs after meals) for best absorption. Can cause harmless red-orange urine discoloration of sweat, tears, saliva, feces and urine. May permanently discolor soft contact lenses. Report: Persistent N/V/D, flu-like symptoms, unusual bruising or bleeding, unusual weakness or fatigue, change in color of stool
What are some patient counseling points for Isoniazid?
Take on empty stomach for best absorption. Avoid alcohol. Avoid tyramine containing foods. Report: Tingling and numbness in extremities, loss of sensation, unusual weakness or fatigue, change in color of stool
What are some patient counseling points for Pyrazinamide?
Take with food. May cause nausea or loss of appetite. Report: Unusual weakness or fatigue, change in color of stool, yellowing of skin or eyes, extreme joint pain
What are some patient counseling points for Ethambutol?
Take with food. Report: numbness or tingling of extremities, changes in vision, any persistent ADRs
What is the management of the common ADR of GI Upset?
Common in the first weeks of therapy. In the presence of GI symptoms, serum AST and bilirubin should be measured. Take w/ food or closer to meal time
What is the management of the common ADR of Rash?
Usually self-limiting. Drugs should be stopped completely when rash accompanied w/ fever or mucous membrane involvement
What is the management of the common ADR of Hepatitis?
3 of the first line drugs (RIF, INH, PZA) can cause drug-induced liver injury. AST: 3x UNL in the presence of symptoms or 5x UNL in the absence of symptoms; 10x UNL is defined as severe. Restart drugs one at a time after AST returns to < 2x UNL. RIF is the least hepatotoxic compared to INH or PZA and most effective therefore should be restarted first
What is Peripheral Neuropathy associated with an increased risk of?
Nutritional deficiency. Diabetes. HIV infection. Renal failure. Alcoholism. Pregnant and breastfeeding women
What is the treatment monitoring for Efficacy?
Monthly sputum for AFB smear and culture (until 2 consecutive cultures negative). Serial sputum smears Q2 weeks to asses early response. Additional drug-susceptibility tests if culture-positive after 3 months of treatment. Periodic (min. montly) evaluation to asses adherence and identify ADRs. Repeat chest X-Ray: At completion of initial treatment phase for patients with initial (-) cultures, At the end of treatment for patients with culture (-) TB, Generally not necessary for patients with culture positive TB
What is the treatment monitoring for Toxicity?
Renal function, AST, ALT, bilirubin, and platelet count if abnormalities at baseline. Visual acuity and color vision monthly if EMB used > 2 months or doses > 15-20mg/kg
What are the “special populations” in TB treatment?
HIV (+), Children, Pregnancy or breastfeeding, Renal insufficiency and ESRD, Hepatic disease
What is the treatment of TB in HIV (+) like?
Same regimens except (d/t Rifamycin-R): Intermittent dosing NOT recommended: e.g, 1) INH-Rifapentine weekly in continuation phase should NOT be used, 2) INH-RIF BIW should NOT be used in pts w/ CD4+ count < 100. DDI between antiretrovirals and Rifamycins (dosage adjustment required, DDI with Rifabutin < Rifampin)
What is TB treatment like in children and adolescents?
Use DOT. < 5 years old w/ 3 drugs in initial phase. EMB is NOT recommended (diff. in performing visual acuity test). Thrice-weekly therapy NOT recommended. Duration: 6 months
What is TB treatment like in pregnancy and breastfeeding?
TREAT when its determined to be moderate to high. Untreated TB poses greater risk to pregnant woman and fetus than no tx. Initial phase treatment regimen should consist of INH, RIF, and EMB. SM should NOT be substituted for EMB. Do NOT recommend PZA (not generally recommended but PZA has been included in regimen w/o reported ADRs). Low concentration of drug in breast milk
What is treatment like in Renal Insufficiency and ESRD?
Some antituberculosis medications are cleared by the kidneys> Dosage should NOT decrease. Dosing INTERVAL should be increased. Most drugs can be given 3x weekly after HD
What is the treatment like with Hepatic disease?
Recommend regimens with fewer hepatotoxic agents. 1) Treatment w/o PZA (initial phase (2 months): INH, RIF, and EMB. Continuation phase (7 months): INH and RIF). 2) Treatment w/o INH (Initial phase (2 months): RIF, PZA, and EMB. Continuation pahse (4 months): RIF, EMB, and PZA). 3) Regimens w/ only 1 potentially hepatotoxic drug: RIF should be retained w/ duration: 12-18 months. 4) Regimens w/ no potentially hepatotoxic drugs: duration of treatment: 18-24 months
Who are at increased risk for infections caused by MDR-TB?
Exposure to a person who has known drug resistant TB. Exposure to a person w/ active TB who has had prior treatment for TB & susceptibility test are not known. Exposure to persons w/ active TB from areas in which there is high prevalence of drug resistance. Exposure to persons who contrinue to have (+) sputum smears after 2 months of combination chemotherapy. Travel in area of high prevalence of drug resistance (i.e. Dominican Republic)
What is the suggested regimens for MDR-TB that is resistant to: INH + RIF (+/- SM)?
PZA, EM, FQ, Amikacin
What is the suggested regimens for MDR-TB that is resistant to: INH + RIF + EM (+/- SM)?
PZA, FQ, Amikacin + 2 additional agents
What is the suggested regimens for MDR-TB that is resistant to: INH + RIF PZA (+/- SM)?
EMB, FQ, Amikacin + 2 additional agents
What is the suggested regimens for MDR-TB that is resistant to: INH + RIF PZA + EMB (+/- SM)?
EMB, FQ, Amikacin + 2 additional agents. Surgery if possible
What are the Group 2 (injectable agents) used?
Kenamycin (Km); Amikacin (Am); Capreomycin (Cm); Streptomycin (S)
What is the role of Surgery in MDR-TB?
Has not been established in randomized studies. Disparity between reports. If surgery is to be done, it should be performed by an experienced surgeon after the patient has received several months of drug therapy. Even with successful resection, 12-24 additional months of chemotherapy should be given
What are the advantages of Fixed-Dose combinations?
1) Minimize inadvertent monotherapy. 2) Decrease the frequency of acquired drug resistance and medication errors. 3) Should be generally be used when therapy can’t be administered under DOT
What are the two combined preparations?
INH and RIF (Rifamate). INH, RIF, and PZA (Rifater)
How is drug completion determined?
Completion primarily defined by number of ingested doses within specific time frame. Specified doses must be administered 1) within 3 months for initial phase, 2) within 6 months for 4-month continuation phase. Consider therapy interrupted if target doses NOT met within specified time period
What is the management of initial phase treatment interruptions?
If lapse > 14 days, start from beginning. If lapse < 14 days, continue treatment to complete total doses warranted (if can be completed w/in 3 months)
What is Extrapulmonary (EP) TB?
More common among children & persons w/ impaired immunity. The same basic principles that underlie the treatment of pulmonary TB applies. 6-9 months regimen include INH and RIF are effective (2 months of RIPE followed by 4-7 months of INH and RIF): TB meningitis duration of treatment is 9-12 months. Corticosteroid is a useful adjunct in treating some forms of EP TB, specifically meningitis and pericarditis caused by drug-susceptible organisms
When is adjunctive use of Corticosteroids (CORT) strongly recommended?
Pericarditis. CNS TB (including meningitis)
What is an important note to remember when treating a patient?
TB should never be treated with a SINGLE drug and a SINGLE drug should never be added to a failing regimen because of the risk of emergence of drug resistance
