Ethambutol is used in the treatment of mycobacterial infections including tuberculosis and atypical mycobacterial infections. It is considered a first-line antituberculosis agent and is used in combination with isoniazid, pyrazinamide, rifampin, and/or streptomycin for treating isoniazid-susceptible organisms and when resistance to isoniazid or rifampin has been confirmed. Ethambutol appears to be more effective and less toxic than other antitubercular agents. Ethambutol was approved by the FDA in 1967.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
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.
Route-Specific Administration
Oral Administration
-May administer with food.
-Tablets may be crushed and mixed with apple juice or applesauce.
Since ethambutol is recommended for use with other antituberculous agents, these adverse reactions may be related to concomitant therapy.
Optic neuritis, manifested by decreased visual acuity (visual impairment / blurred vision), loss of color discrimination (color blindness), constriction of visual fields, and central and peripheral scotomata, is the most significant adverse reaction to ethambutol therapy. Visual changes may be unilateral or bilateral. These visual changes are dose-related and usually reversible over a period of weeks to months following discontinuation of ethambutol therapy. Optic neuritis is most frequently encountered with doses of 25 mg/kg/day and after 2 months of treatment. Patients with cataracts, inflammatory eye conditions, diabetic retinopathy, and optic neuritis should be closely monitored for changes in visual acuity. Some patients have received ethambutol again after such recovery without recurrence of loss of visual acuity. A pretreatment ophthalmologic exam should be performed on these patients, in addition to monthly testing in patients receiving doses greater than 15 mg/kg/day. Irreversible blindness has been reported.
Hepatitis and hepatotoxicity, including fatalities, have been reported with ethambutol. Hepatitis may be part of a hypersensitivity syndrome. Assess hepatic function at baseline and periodically. Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.
Gastrointestinal complaints during ethambutol therapy may include anorexia, nausea, vomiting, gastrointestinal upset, and abdominal pain.
Arthralgia (joint pain) and peripheral neuropathy (peripheral neuritis) with numbness and tingling of the extremities have been reported with ethambutol therapy.
Adverse reactions that have been reported with ethambutol therapy include confusion, disorientation, possible hallucinations, dizziness, and headache.
Fever and malaise can occur with ethambutol therapy.
Leukopenia, neutropenia, and thrombocytopenia have all been reported with ethambutol therapy.
Erythema multiforme has been reported with ethambutol therapy. Dermatitis and pruritus have also occurred.
Hypersensitivity reactions have been reported with ethambutol. Signs and symptoms include rash (unspecified), exfoliative dermatitis, eosinophilia, and one or more of the following: hepatitis, myocarditis, nephritis, pericarditis, pneumonitis. Fever and lymphadenopathy may be present. Anaphylactic/anaphylactoid reactions have also been reported.
Pulmonary infiltrates, with or without eosinophilia (eosinophilic pneumonia), have also been reported with ethambutol therapy.
Hyperuricemia, with or without precipitation of gout, can occur with ethambutol therapy.
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.
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 including fatalities has been reported with ethambutol. Assess hepatic function at baseline and periodically. Most combination therapy for active TB disease includes more than 1 agent that may contribute to hepatotoxicity.
Optimal ethambutol dosing for obesity is not established. Ethambutol dosing is based on lean body weight, in general.
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.
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. Previous American Academy of Pediatrics recommendations considered ethambutol to be usually compatible with breast-feeding. 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.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Mycobacterium sp., Mycobacterium tuberculosis
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
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. Ethambutol is generally recommended as part of the initial 2-month intensive phase of treatment as first-line therapy.
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. Alternatively, 15 to 25 mg/kg/dose PO once daily or 25 to 40 mg/kg/dose PO 3 days/week. The FDA-approved dosage 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 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.
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. Alternatively, 15 to 25 mg/kg/dose PO once daily or 25 to 40 mg/kg/dose PO 3 days/week. The FDA-approved dosage 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 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.
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. Alternatively, 15 to 25 mg/kg/dose PO once daily or 25 to 40 mg/kg/dose PO 3 days/week. The FDA-approved dosage 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 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.
Adolescents: 15 to 25 mg/kg/dose (lean body weight) (Max: 1.6 g/dose) PO once daily or 5 days/week, or alternatively, 25 to 50 mg/kg/dose (lean body weight) (Max: 2.4 g/dose) PO 3 days/week or 50 mg/kg/dose (lean body weight) (Max: 4 g/dose) PO twice weekly. The FDA-approved dosage 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, 30 to 50 mg/kg/dose (lean body weight) (Max: 2.4 g/dose) PO 3 days/week or 50 mg/kg/dose (lean body weight) (Max: 4 g/dose) PO twice weekly. 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.
-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 dosage 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. The FDA-approved dosage 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 56 to 75 kg (lean body weight): 1.2 g PO once daily or 5 days/week. The FDA-approved dosage 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. The FDA-approved dosage 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. The FDA-approved dosage 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. 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.
-for the treatment of CNS-related tuberculosis as part of shortened intensive combination therapy*:
Oral dosage:
Infants, Children, and Adolescents: 17.5 to 22.5 mg/kg/dose PO once daily.
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 dosage 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 dosage 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.
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.
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.
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.
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.
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.
Maximum Dosage Limits:
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.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Reduce ethambutol dose in patients with renal impairment, since the main path of excretion of this drug is by the kidneys.
Adult patients*
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*
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*
15 to 25 mg/kg/dose PO 3 days/week after hemodialysis. Consider therapeutic drug monitoring to guide optimal dosing.
Pediatric patients*
15 to 25 mg/kg/dose PO every 48 hours.
Peritoneal dialysis*
Adult patients*
15 to 25 mg/kg/dose PO every 48 hours.
Pediatric patients*
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.
Adult patients*
15 to 25 mg/kg/dose PO every 24 to 36 hours.
Pediatric patients*
No dosage adjustment needed.
*non-FDA-approved indication
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.
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.
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.
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.
-Route-Specific Pharmacokinetics
Oral Route
Approximately 75-80% of an ethambutol oral dose is absorbed. Peak serum levels are attained within 2-4 hours.