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  • CLASSES

    Other Agents for Tuberculosis

    DEA CLASS

    Rx

    DESCRIPTION

    Used for mycobacterial infections including tuberculosis and atypical mycobacterial infections. First-line antituberculosis agent in combination with isoniazid, pyrazinamide, rifampin, and/or streptomycin. Appears to be more effective and less toxic than other antitubercular agents.

    COMMON BRAND NAMES

    Myambutol

    HOW SUPPLIED

    Ethambutol/Ethambutol Hydrochloride/Myambutol Oral Tab: 100mg, 400mg

    DOSAGE & INDICATIONS

    For the treatment of drug-susceptible tuberculosis infection as part of combination therapy.
    For the treatment of drug-susceptible tuberculosis infection in persons without HIV as part of combination therapy.
    Oral dosage
    Adults weighing more than 90 kg (treatment-naive)

    15 mg/kg/dose (Max: 1.5 g/dose) PO once daily.[28263] Ethambutol is generally recommended as part of the initial 2-month intensive phase of treatment as first-line therapy.[61094] [65619]

    Adults weighing more than 90 kg (retreatment)

    25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily. Ethambutol is generally recommended as part of the initial 2-month intensive phase of treatment as first-line therapy.

    Adults weighing 76 to 90 kg (lean body weight)

    1.6 g PO once daily or 5 days/week, or alternatively, 2.4 g PO 3 days/week or 4 g PO twice weekly.[61094] The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy.[28263] Daily dosing is preferred and is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.[61094] [65619]

    Adults weighing 56 to 75 kg (lean body weight)

    1.2 g PO once daily or 5 days/week, or alternatively, 2 g PO 3 days/week or 2.8 g PO twice weekly.[61094] The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy.[28263] Daily dosing is preferred and is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.[61094] [65619]

    Adults weighing 40 to 55 kg (lean body weight)

    800 mg PO once daily or 5 days/week, or alternatively, 1.2 g PO 3 days/week or 2 g PO twice weekly.[61094] The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy.[28263] Daily dosing is preferred and is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.[61094] [65619]

    Adolescents

    15 to 25 mg/kg/dose (lean body weight) (Max: 1.6 g/dose) PO once daily or 5 days/week, or alternatively, 50 mg/kg/dose (lean body weight) PO 3 days/week (Max: 2.4 g/dose) or twice weekly (Max: 4 g/dose).[61094] The FDA-approved dose is 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (lean body weight) (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy. Daily dosing is preferred and is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.

    Infants† and Children†

    15 to 25 mg/kg/dose (lean body weight) (Max: 1.6 g/dose) PO once daily or 5 days/week, or alternatively, 50 mg/kg/dose (lean body weight) PO 3 days/week (Max: 2.4 g/dose) or twice weekly (Max: 4 g/dose).[61094] Daily dosing is preferred and is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.

    Neonates†

    15 to 25 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Ethambutol is rarely recommended as part of the initial 2-month intensive phase of treatment due to the potential for optic neuritis and red-green color blindness.[53484] [53485] [61095] [65675]

    For the treatment of drug-susceptible tuberculosis infection in persons living with HIV as part of combination therapy.
    Oral dosage
    Adults weighing more than 90 kg (lean body weight)

    1.6 g PO once daily. Monitor response and consider therapeutic drug monitoring to assure dosing adequacy. The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.

    Adults weighing 76 to 90 kg (lean body weight)

    1.6 g PO once daily or 5 days/week.[34362] [61094] The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy.[28263] Daily dosing is defined as 5- or 7 days/week.[61094] Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.[34362] [61094] [65619]

    Adults weighing 56 to 75 kg (lean body weight)

    1.2 g PO once daily or 5 days/week. [61094] The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy. Daily dosing is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.

    Adults weighing 40 to 55 kg (lean body weight)

    800 mg PO once daily or 5 days/week. [61094] The FDA-approved dose is 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy. Daily dosing is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.

    Adolescents

    15 to 25 mg/kg/dose (lean body weight) (Max: 1.6 g/dose) PO once daily or 5 days/week. [61094] The FDA-approved dose is 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (lean body weight) (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy. Ethambutol is generally recommended as part of the initial 2-month intensive phase of treatment as first-line therapy.

    Infants† and Children†

    15 to 25 mg/kg/dose (lean body weight) (Max: 1.6 g/dose) PO once daily or 5 days/week. [61094] Daily dosing is defined as 5- or 7 days/week. Ethambutol is generally recommended as part of the initial 2-month intensive phase as first-line therapy.

    Neonates†

    15 to 25 mg/kg/dose PO once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Ethambutol is rarely recommended as part of the initial 2-month intensive phase due to the potential for optic neuritis and red-green color blindness.[53484]

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy.
    Oral dosage
    Adults

    15 to 25 mg/kg/dose (lean body weight) PO once daily. The FDA-approved dose is 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (lean body weight) (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy.

    Adolescents

    15 to 25 mg/kg/dose (lean body weight) PO once daily.   The FDA-approved dose is 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in treatment-naive patients and 25 mg/kg/dose (lean body weight) (Max: 2.5 g/dose) PO once daily for 60 days, then 15 mg/kg/dose (lean body weight) (Max: 1.5 g/dose) PO once daily in patients who have previously received therapy.

    Infants† and Children†

    15 to 25 mg/kg/dose (lean body weight) PO once daily.

    For the treatment of Mycobacterium avium complex infection† (MAC) in persons with HIV.
    Oral dosage
    Adults

    15 mg/kg/dose PO once daily plus clarithromycin or azithromycin. May consider addition of third or fourth drug (rifabutin, amikacin, streptomycin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Adolescents

    15 mg/kg/dose PO once daily plus clarithromycin or azithromycin. May consider addition of third or fourth drug (rifabutin, amikacin, streptomycin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Infants and Children

    15 to 25 mg/kg/dose PO once daily (Max: 2.5 g/day) plus clarithromycin or azithromycin. For severe disease, consider adding rifabutin. If rifabutin cannot be administered or if a fourth drug is needed for patients with more severe symptoms or disseminated disease, consider adding ciprofloxacin, levofloxacin, or amikacin. Duration of treatment depends on clinical response but should continue for at least 12 months.[34361]

    For secondary Mycobacterium avium complex (MAC) prophylaxis† in persons with HIV with disseminated disease after treatment of the acute illness.
    Oral dosage
    Adults

    15 mg/kg/dose PO once daily plus clarithromycin or azithromycin. May consider addition of third or fourth drug (rifabutin, amikacin, streptomycin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Consider discontinuing secondary prophylaxis in patients who have completed at least 12 months of MAC treatment, have no signs or symptoms of MAC, and have a sustained (more than 6 months) CD4 count more than 100 cells/mm3 in response to ART. Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34362]

    Adolescents

    15 mg/kg/dose PO once daily plus clarithromycin or azithromycin. May consider addition of third or fourth drug (rifabutin, amikacin, streptomycin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Consider discontinuing secondary prophylaxis in patients who have completed at least 12 months of MAC treatment, have no signs or symptoms of MAC, and have a sustained (more than 6 months) CD4 count more than 100 cells/mm3 in response to ART. Restart secondary prophylaxis if the CD4 count decreases to less than 100 cells/mm3.[34362]

    Infants and Children

    15 to 25 mg/kg/dose PO once daily (Max: 2.5 g/day) plus clarithromycin or azithromycin with rifabutin for children older than 5 years who received rifabutin as part of initial treatment. Do not discontinue secondary prophylaxis for children younger than 2 years. Consider discontinuing secondary prophylaxis in children older than 2 years who have received at least 12 months of MAC treatment, have no signs or symptoms of MAC, have been receiving stable antiretroviral therapy, and have a sustained (more than 6 months) CD4 count more than 200 cells/mm3 for children 2 to 5 years and more than 100 cells/mm3 for children 6 years and older. Restart secondary prophylaxis if the CD4 count falls below these thresholds.[34361]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Dosing is based on lean body weight.

    Adults

    25 mg/kg/dose (Max: 2.5 g/dose) PO once daily is the FDA-approved maximum dosage. Other regimens and maximum dosages have been used off-label.
    Weighing more than 90 kg: 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily.
    Weighing 76 to 90 kg: 1.6 g PO once daily or 5 days/week, 2.4 g PO 3 days/week, or 4 g PO twice weekly.
    Weighing 56 to 75 kg: 1.2 g PO once daily or 5 days/week, 2 g PO 3 days/week, or 2.8 g PO twice weekly.
    Weighing 40 to 55 kg: 800 mg PO once daily or 5 days/week, 1.2 g PO 3 days/week, or 2 g PO twice weekly.

    Geriatric

    25 mg/kg/dose (Max: 2.5 g/dose) PO once daily is the FDA-approved maximum dosage. Other regimens and maximum dosages have been used off-label.
    Weighing more than 90 kg: 25 mg/kg/dose (Max: 2.5 g/dose) PO once daily.
    Weighing 76 to 90 kg: 1.6 g PO once daily or 5 days/week, 2.4 g PO 3 days/week, or 4 g PO twice weekly.
    Weighing 56 to 75 kg: 1.2 g PO once daily or 5 days/week, 2 g PO 3 days/week, or 2.8 g PO twice weekly.
    Weighing 40 to 55 kg: 800 mg PO once daily or 5 days/week, 1.2 g PO 3 days/week, or 2 g PO twice weekly.

    Adolescents

    25 mg/kg/dose (Max: 2.5 g/dose) PO once daily is the FDA-approved maximum dose. 25 mg/kg/dose (Max: 1.6 g/dose) PO once daily or 5 days/week or 50 mg/kg/dose PO 3 days/week (Max: 2.4 g/dose) or twice weekly (Max: 4 g/dose) has been used off-label.

    Children

    Safety and efficacy have not been established. 25 mg/kg/dose (Max: 1.6 g) PO once daily or 5 days/week or 50 mg/kg/dose PO 3 days/week (Max: 2.4 g/dose) or twice weekly (Max: 4 g/dose) has been used off-label.

    Infants

    Safety and efficacy have not been established. 25 mg/kg/dose PO once daily or 5 days/week or 50 mg/kg/dose PO 3 days/week or twice weekly has been used off-label.

    Neonates

    Safety and efficacy have not been established. 25 mg/kg/dose PO once daily has been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Reduce ethambutol dose in patients with renal impairment, since the main path of excretion of this drug is by the kidneys.[28263]
     
    Adult patients† [34362] [61094] [65465]
    CrCl 30 mL/minute or more: No dosage adjustment needed.
    CrCl less than 30 mL/minute: 15 to 25 mg/kg/dose PO 3 days/week. Consider therapeutic drug monitoring to guide optimal dosing.
     
    Pediatric patients† [32569]
    GFR 30 mL/minute/1.73 m3 or more: No dosage adjustment needed
    GFR 10 to 29 mL/minute/1.73 m3: 15 to 25 mg/kg/dose PO every 36 hours.
    GFR less than 10 mL/minute/1.73 m3: 15 to 25 mg/kg/dose PO every 48 hours.
     
    Intermittent hemodialysis†
    Adult patients† [34362] [61094]
    15 to 25 mg/kg/dose PO 3 days/week after hemodialysis. Consider therapeutic drug monitoring to guide optimal dosing.
     
    Pediatric patients† [32569]
    15 to 25 mg/kg/dose PO every 48 hours.
     
    Peritoneal dialysis†
    Adult patients† [32569]
    15 to 25 mg/kg/dose PO every 48 hours.
     
    Pediatric patients† [32569]
    15 to 25 mg/kg/dose PO every 48 hours.
     
    Continuous renal replacement therapy (CRRT)†NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303]
     
    Adult patients† [32569]
    15 to 25 mg/kg/dose PO every 24 to 36 hours.
     
    Pediatric patients† [32569]
    No dosage adjustment needed.

    ADMINISTRATION

     
    Tuberculosis
    Directly observed therapy (DOT) is recommended for all children as well as adolescents and adults living with HIV and any regimen consisting of intermittent therapy.[34361] [34362] [61094]

    Oral Administration

    May administer with food.
    Tablets may be crushed and mixed with apple juice or applesauce.

    STORAGE

    Myambutol:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Renal impairment

    Reduce ethambutol dose in patients with renal impairment, since the main path of excretion of this drug is by the kidneys. Assess renal function at baseline and periodically.[28263]

    Cataracts, children, diabetic retinopathy, infants, loss of consciousness, neonates, optic neuritis

    Ethambutol is contraindicated in patients with known optic neuritis unless clinical judgment determines that it may be used. Ethambutol is also contraindicated in patients who are unable to appreciate and report visual side effects or changes in vision (e.g., young children, infants, neonates, loss of consciousness). Because this drug may have adverse effects on vision, physical examination should include ophthalmoscopy, finger perimetry, and testing of color discrimination. Perform visual acuity testing before beginning ethambutol therapy and periodically during drug administration; it should be done monthly when a patient is receiving more than 15 mg/kg/day. In patients with visual defects such as cataracts, recurrent inflammatory conditions of the eye, optic neuritis, and diabetic retinopathy, the evaluation of changes in visual acuity is more difficult; take care to be sure the variations in vision are not due to the underlying disease conditions. In such patients, consider the relationship between benefits expected and possible visual deterioration since evaluation of visual changes is difficult.

    Hepatotoxicity

    Hepatotoxicity including fatalities has been reported with ethambutol. Assess hepatic function at baseline and periodically.[28263] Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.[61094]

    Obesity

    Optimal ethambutol dosing for obesity is not established. Ethambutol dosing is based on lean body weight, in general.

    Acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection

    Do not treat persons with tuberculosis (TB) and human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS) with intermittent (i.e., twice weekly or 3 days/week) TB treatment regimens to avoid recurrent disease and the emergence of drug resistance.[34361] [34362] [61094]

    Pregnancy

    Use ethambutol during pregnancy only if the benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of ethambutol use in pregnant women. There are reports of ophthalmic abnormalities occurring in infants born to women on antituberculosis therapy that included ethambutol. Ethambutol has been shown to be teratogenic in animal studies when given in high doses. Tuberculosis guidelines support treatment initiation in pregnancy whenever the probability of maternal disease is moderate to high due to the risk of untreated tuberculosis to a pregnant woman and her fetus.

    Breast-feeding

    Use ethambutol during breast-feeding only if the expected benefit to the mother outweighs the potential risk to the fetus. Ethambutol is distributed into human breast milk.[28263] Previous American Academy of Pediatrics recommendations considered ethambutol to be usually compatible with breast-feeding.[27500] Tuberculosis guidelines encourage breast-feeding for women who are noninfectious and being treated with first-line agents, such as ethambutol, as the small concentrations of these drugs measured in breast milk have not been reported to produce toxic effects in the nursing infant.[61094]

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / 0-1.0
    optic neuritis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    myocarditis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    eosinophilic pneumonia / Delayed / Incidence not known

    Moderate

    scotomata / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    hepatitis / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hallucinations / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    gout / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known

    Mild

    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    headache / Early / Incidence not known
    dizziness / Early / Incidence not known
    fever / Early / Incidence not known
    malaise / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Aluminum Hydroxide: (Moderate) Aluminum hydroxide can reduce the rate or extent of ethambutol absorption. At least 4 hours should elapse between doses of aluminum hydroxide-containing antacids and ethambutol.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Aluminum hydroxide can reduce the rate or extent of ethambutol absorption. At least 4 hours should elapse between doses of aluminum hydroxide-containing antacids and ethambutol.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Aluminum hydroxide can reduce the rate or extent of ethambutol absorption. At least 4 hours should elapse between doses of aluminum hydroxide-containing antacids and ethambutol.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Aluminum hydroxide can reduce the rate or extent of ethambutol absorption. At least 4 hours should elapse between doses of aluminum hydroxide-containing antacids and ethambutol.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Aluminum hydroxide can reduce the rate or extent of ethambutol absorption. At least 4 hours should elapse between doses of aluminum hydroxide-containing antacids and ethambutol.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of aminosalicylate sodium, aminosalicylic acid and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Urinary concentrations of ethambutol could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Capreomycin: (Moderate) Adverse hepatic effects have been associated with capreomycin, especially with concurrent use of other antituberculosis drugs known to alter hepatic function. Theoretically, coadministration of capreomycin and ethambutol could increase the risk of hepatotoxicity. Monitor patients for changes in liver function if these drugs are coadministered.
    Ethionamide: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of ethionamide and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs may be used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Isoniazid, INH: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of ethambutol and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of ethambutol and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of pyrazinamide, PZA and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.[. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Isoniazid, INH; Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of ethambutol and isoniazid, INH. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program. (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifabutin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Probenecid: (Moderate) Probenecid has uricosuric actions. Ethambutol can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethambutol is administered to patients being treated with probenecid.
    Probenecid; Colchicine: (Moderate) Probenecid has uricosuric actions. Ethambutol can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethambutol is administered to patients being treated with probenecid.
    Pyrazinamide, PZA: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of pyrazinamide, PZA and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.[.
    Rifabutin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifabutin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Rifampin: (Moderate) Careful monitoring of hepatic function is recommended with the concurrent use of rifampin and ethambutol. Each drug has the potential to cause hepatotoxicity, and hepatotoxicity risk may be increased with concomitant use. These drugs are often used together for the treatment of active tuberculosis (TB) infection, and patients should also be assessed for additional risk factors for hepatotoxicity, such as other hepatotoxic drugs, alcohol use, and underlying hepatic disease. Any adverse event leading to hospitalization or death should be reported to local or state health departments as well as the FDA MedWatch program.
    Sulfinpyrazone: (Minor) Because ethambutol can cause hyperuricemia, it may counteract the uricosuric effects of sulfinpyrazone. Dosage adjustments of sulfinpyrazone may be necessary if these agents are administered concurrently to patients with gout.
    Vigabatrin: (Major) Vigabatrin should not be used with ethambutol, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.

    PREGNANCY AND LACTATION

    Pregnancy

    Use ethambutol during pregnancy only if the benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies of ethambutol use in pregnant women. There are reports of ophthalmic abnormalities occurring in infants born to women on antituberculosis therapy that included ethambutol. Ethambutol has been shown to be teratogenic in animal studies when given in high doses. Tuberculosis guidelines support treatment initiation in pregnancy whenever the probability of maternal disease is moderate to high due to the risk of untreated tuberculosis to a pregnant woman and her fetus.

    Use ethambutol during breast-feeding only if the expected benefit to the mother outweighs the potential risk to the fetus. Ethambutol is distributed into human breast milk.[28263] Previous American Academy of Pediatrics recommendations considered ethambutol to be usually compatible with breast-feeding.[27500] Tuberculosis guidelines encourage breast-feeding for women who are noninfectious and being treated with first-line agents, such as ethambutol, as the small concentrations of these drugs measured in breast milk have not been reported to produce toxic effects in the nursing infant.[61094]

    MECHANISM OF ACTION

    Ethambutol is primarily bacteriostatic, although in higher doses it also exhibits bactericidal properties. The exact mechanism is not known; however, it appears to inhibit RNA synthesis, resulting in impaired cellular metabolism and multiplication. Ethambutol is effective only against bacilli that are actively dividing. Cross-resistance between ethambutol and other antitubercular agents has not been demonstrated.
     
    In general, the following organisms are susceptible to ethambutol: M. tuberculosis; M. bovis; M. marinum; and some strains of M. kansasii, M. avium, M. fortuitum, and M. intracellulare.

    PHARMACOKINETICS

    Ethambutol is administered orally. Ethambutol is widely distributed, with high concentrations in the kidneys, lungs, and saliva. It penetrates inflamed meninges (10—50%) to reach therapeutic levels in the CSF. The drug crosses the placenta, resulting in plasma fetal concentrations that are 30% of maternal concentrations, and is distributed into breast milk in amounts similar to maternal plasma levels. Ethambutol is partially metabolized in the liver. The parent drug and its metabolites are excreted primarily in the urine (65%), with the remaining 20—25% excreted unchanged in the feces. The elimination half-life is 3.5 hours and can be up to 15 hours in renal disease.

    Oral Route

    Approximately 75—80% of an ethambutol oral dose is absorbed. Peak serum levels are attained within 2—4 hours.