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Anti-mycobacterial Agents
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Ethambutol
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Use Treatment of tuberculosis and other mycobacterial diseases in conjunction with other antituberculosis agents Mechanism of Action Suppresses mycobacteria multiplication by interfering with RNA synthesis ------------------------------------------------- Dosing: Oral: Treatment of tuberculosis: Note: Used as part of a multidrug regimen. Treatment regimens consist of an initial 2 month phase, followed by a continuation phase of 4 or 7 additional months; frequency of dosing may differ depending on phase of therapy. Children: Daily therapy: 15-20 mg/kg/day (maximum: 1 g/day). Twice weekly directly observed therapy (DOT): 50 mg/kg (maximum: 4 g/dose) . Adults (suggested doses by lean body weight): Daily therapy: 15-25 mg/kg 40-55 kg: 800 mg 56-75 kg: 1200 mg 76-90 kg: 1600 mg (maximum dose regardless of weight) Twice weekly directly observed therapy (DOT): 50 mg/kg 40-55 kg: 2000 mg 56-75 kg: 2800 mg 76-90 kg: 4000 mg (maximum dose regardless of weight) Three times/week DOT: 25-30 mg/kg (maximum: 2.5 g) 40-55 kg: 1200 mg 56-75 kg: 2000 mg 76-90 kg: 2400 mg (maximum dose regardless of weight) Disseminated Mycobacterium avium complex (MAC) in patients with advanced HIV infection: 15 mg/kg ethambutol in combination with azithromycin 600 mg daily ------------------------------------------------- Dosing interval in renal impairment: Clcr 10-50 mL/minute: Administer every 24-36 hours Clcr<10 mL/minute: Administer every 48 hours Hemodialysis: Slightly dialyzable (5% to 20%); Administer dose postdialysis Peritoneal dialysis: Dose for Clcr<10 mL/minute Continuous arteriovenous or venovenous hemofiltration: Administer every 24-36 hours ------------------------------------------------- Monitoring Baseline and periodic (monthly) visual testing (each eye individually, as well as both eyes tested together) in patients receiving >15 mg/kg/day; baseline and periodic renal, hepatic, and hematopoietic tests Supplied: Tablet, as hydrochloride: 100 mg, 400 mg |
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Isoniazid
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Indications: Treatment of susceptible tuberculosis infections; treatment of latent tuberculosis infection (LTBI) Mechanism of Action Unknown, but may include the inhibition of myocolic acid synthesis resulting in disruption of the bacterial cell wall --------------------------------------------------- Dosing: Recommendations often change due to resistant strains and newly-developed information; consult MMWR for current CDC recommendations: Oral (injectable is available for patients who are unable to either take or absorb oral therapy): Infants and Children: Treatment of latent TB infection (LTBI): 10-20 mg/kg/day in 1-2 divided doses (maximum: 300 mg/day) or 20-40 mg/kg (maximum: 900 mg/dose) twice weekly for 9 months Treatment of active TB infection: Daily therapy: 10-15 mg/kg/day in 1-2 divided doses (maximum: 300 mg/day). Twice weekly directly observed therapy (DOT): 20-30 mg/kg (maximum: 900 mg). Adults: Treatment of latent tuberculosis infection (LTBI): 300 mg/day or 900 mg twice weekly for 6-9 months in patients who do not have HIV infection (9 months is optimal, 6 months may be considered to reduce costs of therapy) and 9 months in patients who have HIV infection. Extend to 12 months of therapy if interruptions in treatment occur. Treatment of active TB infection (drug susceptible): Daily therapy: 5 mg/kg/day given daily (usual dose: 300 mg/day); 10 mg/kg/day in 1-2 divided doses in patients with disseminated disease Twice weekly directly observed therapy (DOT): 15 mg/kg (maximum: 900 mg); 3 times/week therapy: 15 mg/kg (maximum: 900 mg) Note: Treatment may be defined by the number of doses administered (eg, "six-month" therapy involves 192 doses of INH and rifampin, and 56 doses of pyrazinamide). Six months is the shortest interval of time over which these doses may be administered, assuming no interruption of therapy. NNote: Concomitant administration of 6-50 mg/day pyridoxine is recommended in malnourished patients or those prone to neuropathy (eg, alcoholics, diabetics) --------------------------------------------------- Dosing adjustment in renal impairment: Clcr<10 mL/minute: Administer 50% of normal dose Hemodialysis: Dialyzable (50% to 100%) Administer dose ostdialysis PPeritoneal dialysis, continuous arteriovenous or venovenous hemofiltration: Dose for Clcr<10 mL/minute Dosing adjustment in hepatic impairment: Dose should be reduced in severe hepatic disease --------------------------------------------------- Monitoring Periodic liver function tests; sputum cultures monthly (until 2 consecutive negative cultures reported); monitoring for prodromal signs of hepatitis --------------------------------------------------- Supplied: Syrup: 50 mg/5 mL (473 mL) Tablet: 100 mg, 300 mg |
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Pyrazinamide
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Indication: Adjunctive treatment of tuberculosis in combination with other antituberculosis agents Mechanism of Action Converted to pyrazinoic acid in susceptible strains of Mycobacterium which lowers the pH of the environment; exact mechanism of action has not been elucidated --------------------------------- Dosage Oral: Treatment of tuberculosis: Note: Used as part of a multidrug regimen. Treatment regimens consist of an initial 2-month phase, followed by a continuation phase of 4 or 7 additional months; frequency of dosing may differ depending on phase of therapy. Children: Daily therapy: 15-30 mg/kg/day (maximum: 2 g/day) Twice weekly directly observed therapy (DOT): 50 mg/kg/dose (maximum: 4 g/dose) Adults (dosing is based on lean body weight): Daily therapy: 15-30 mg/kg/day 40-55 kg: 1000 mg 56-75 kg: 1500 mg 76-90 kg: 2000 mg (maximum dose regardless of weight) Twice weekly directly observed therapy (DOT): 50 mg/kg 40-55 kg: 2000 mg 56-75 kg: 3000 mg 76-90 kg: 4000 mg (maximum dose regardless of weight) Three times/week DOT: 25-30 mg/kg (maximum: 2.5 g) 40-55 kg: 1500 mg 56-75 kg: 2500 mg 76-90 kg: 3000 mg (maximum dose regardless of weight) Elderly: Start with a lower daily dose (15 mg/kg) and increase as tolerated. --------------------------------- Dosing adjustment in renal impairment: Clcr<50 mL/minute: Avoid use or reduce dose to 12-20 mg/kg/day Avoid use in hemo- and peritoneal dialysis as well as continuous arteriovenous or venovenous hemofiltration. Dosing adjustment in hepatic impairment: Reduce dose --------------------------------- Monitoring Periodic liver function tests, serum uric acid, sputum culture, chest x-ray 2-3 months into treatment and at completion --------------------------------- Supplied: Tablet: 500 mg |
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rifabutin (Mycobutin):
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Prevention of disseminated Mycobacterium avium complex (MAC) in patients
with advanced HIV infection Mechanism of Action Inhibits DNA-dependent RNA polymerase at the beta subunit which prevents chain initiation --------------------------------- Dosing: Oral: Children >1 year: Prophylaxis: 5 mg/kg daily; higher dosages have been used in limited trials Treatment (unlabeled use): Patients not receiving NNRTIs or protease inhibitors: Initial phase (2 weeks to 2 months): 10-20 mg/kg daily (maximum: 300 mg). Second phase: 10-20 mg/kg daily (maximum: 300 mg) or twice weekly Adults: Prophylaxis: 300 mg once daily (alone or in combination with azithromycin) Treatment (unlabeled use): Patients not receiving NNRTIs or protease inhibitors: Initial phase: 5 mg/kg daily (maximum: 300 mg) Second phase: 5 mg/kg daily or twice weekly Patients receiving nelfinavir, amprenavir, indinavir: Reduce dose to 150 mg/day; no change in dose if administered twice weekly Dosage adjustment in renal impairment: Clcr<30 mL/minute: Reduce dose by 50% --------------------------------- Monitoring Periodic liver function tests, CBC with differential, platelet count --------------------------------- Supplied: Capsule: 150 mg |
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Rifamate (INH 150mg + rifampin 300mg):
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[Management of active tuberculosis.] Dosing (Adults): 2 capsules orally once daily. Supplied: Capsule: Rifampin 300 mg and isoniazid 150 mg |
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Rifampin
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Management of active tuberculosis in combination with other agents;
elimination of meningococci from the nasopharynx in asymptomatic
carriers Mechanism of Action Inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription ------------------------------------------------------- Dosing: Oral (I.V. infusion dose is the same as for the oral route): Tuberculosis therapy (drug susceptible): Note: A four-drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol) is preferred for the initial, empiric treatment of TB. When the drug susceptibility results are available, the regimen should be altered as appropriate. Infants and Children <12 years: Daily therapy: 10-20 mg/kg/day usually as a single dose (maximum: 600 mg/day) Twice weekly directly observed therapy (DOT): 10-20 mg/kg (maximum: 600 mg) Adults: Daily therapy: 10 mg/kg/day (maximum: 600 mg/day) Twice weekly directly observed therapy (DOT): 10 mg/kg (maximum: 600 mg); 3 times/week: 10 mg/kg (maximum: 600 mg) Latent tuberculosis infection (LTBI): As an alternative to isoniazid: Children: 10-20 mg/kg/day (maximum: 600 mg/day) for 6 months Adults: 10 mg/kg/day (maximum: 600 mg/day) for 4 months. Note: Combination with pyrazinamide should not generally be offered ( MMWR , Aug 8, 2003). H. influenzae prophylaxis (unlabeled use): Infants and Children: 20 mg/kg/day every 24 hours for 4 days, not to exceed 600 mg/dose Adults: 600 mg every 24 hours for 4 days Meningococcal meningitis prophylaxis: Adults: 600 mg every 12 hours for 2 days Nasal carriers of Staphylococcus aureus (unlabeled use): Children: 15 mg/kg/day divided every 12 hours for 5-10 days in combination with other antibiotics Adults: 600 mg/day for 5-10 days in combination with other antibiotics Synergy for Staphylococcus aureus infections (unlabeled use): Adults: 300-600 mg twice daily with other antibiotics ------------------------------------------------------- Dosing adjustment in hepatic impairment: Dose reductions may be necessary to reduce hepatotoxicity Hemodialysis or peritoneal dialysis: Plasma rifampin concentrations are not significantly affected by hemodialysis or peritoneal dialysis. ------------------------------------------------------- Administration I.V.: Administer I.V. preparation once daily by slow I.V. infusion over 30 minutes to 3 hours at a final concentration not to exceed 6 mg/mL. Oral: Administer on an empty stomach (ie, 1 hour prior to, or 2 hours after meals or antacids) to increase total absorption. The compounded oral suspension must be shaken well before using. May mix contents of capsule with applesauce or jelly. ------------------------------------------------------- Monitoring Periodic (baseline and every 2-4 weeks during therapy) monitoring of liver function (AST, ALT, bilirubin), CBC; hepatic status and mental status, sputum culture, chest x-ray 2-3 months into treatment ------------------------------------------------------- Supplied: Capsule (Rifadin®): 150 mg, 300 mg Injection, powder for reconstitution (Rifadin®): 600 mg |
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Rifapentine (Priftin):
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Cyclopentyl derivative of rifampin (longer
duration of action and greater efficacy compared to rifampin)
Treatment of pulmonary tuberculosis; rifapentine must always be used in conjunction with at least one other antituberculosis drug to which the isolate is susceptible; it may also be necessary to add a third agent (either streptomycin or ethambutol) until susceptibility is known. Mechanism of Action Inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis (but not in mammalian cells). Rifapentine is bactericidal against both intracellular and extracellular MTB organisms. MTB resistant to other rifamycins including rifampin are likely to be resistant to rifapentine. Cross-resistance does not appear between rifapentine and other nonrifamycin antimycobacterial agents. ------------------------------------------------------- Dosing: Adults: Rifapentine should not be used alone ; initial phase should include a 3- to 4-drug regimen Intensive phase (initial 2 months) of short-term therapy: 600 mg (four 150 mg tablets) given twice weekly (with an interval of not less than 72 hours between doses); following the intensive phase, treatment should continue with rifapentine 600 mg once weekly for 4 months in combination with INH or appropriate agent for susceptible organisms ------------------------------------------------------- Supplied: Tablet [film coated]: 150 mg |
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Rifater
(INH 50mg+ rifampin 120mg +pyr 300mg):
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Management of active tuberculosis: Dosing: Adults: Oral: Patients weighing: </= 44 kg: 4 tablets 45-54 kg: 5 tablets >/= 55 kg: 6 tablets Doses should be administered in a single daily dose. Administer dose either 1 hour before or 2 hours after a meal with a full glass of water. ------------------------------------------------------ Supplied: Tablet: Rifampin 120 mg, isoniazid 50 mg, and pyrazinamide 300 mg |
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Measuring Induration (TB Test)
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Disclaimer |
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Listed dosages are for - Adult patients ONLY. PLEASE READ THE
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GlobalRPH does not directly or indirectly practice medicine or provide
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any diagnosis or treatment made in reliance thereon. David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc. |
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