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Pronunciation

(e THAM byoo tole)

Generic Available (U.S.)

Yes

Index Terms

• Ethambutol Hydrochloride

Brand Names: U.S.

• Myambutol®

Brand Names: Canada

• Etibi®

Pharmacologic Category

• Antitubercular Agent

Pharmacologic Category Synonyms

• Tuberculosis Treatment Agent

Use: Labeled Indications

Treatment of pulmonary tuberculosis in conjunction with other antituberculosis agents

Use: Unlabeled

Other mycobacterial diseases in conjunction with other antimycobacterial agents

Pregnancy Risk Factor

C

Pregnancy Considerations

Teratogenic effects have been seen in animals. There are no adequate and well-controlled studies in pregnant women; there have been reports of ophthalmic abnormalities in infants born to women receiving ethambutol as a component of antituberculous therapy. Use only during pregnancy if benefits outweigh risks.

Lactation

Enters breast milk/use caution (AAP considers “compatible”; AAP 2001 update pending)

Breast-Feeding Considerations

The manufacturer suggests use during breast-feeding only if benefits to the mother outweigh the possible risk to the infant. Some references suggest that exposure to the infant is low and does not produce toxicity, and breast-feeding should not be discouraged. Other references recommend if breast-feeding, monitor the infant for rash, malaise, nausea, or vomiting.

Contraindications

Hypersensitivity to ethambutol or any component of the formulation; optic neuritis (risk vs benefit decision); use in young children, unconscious patients, or any other patient who may be unable to discern and report visual changes

Warnings/Precautions

Concerns related to adverse effects:

• Hepatic toxicity: Has been reported, possibly due to concurrent therapy. Monitor liver function prior to and during treatment.

• Optic neuritis: May cause optic neuritis (unilateral or bilateral), resulting in decreased visual acuity or other vision changes. Discontinue promptly in patients with changes in vision, color blindness, or visual defects (effects normally reversible, but reversal may require up to a year). Irreversible blindness has been reported. Monitor visual acuity prior to and during therapy.

Disease-related concerns:

• Ocular disease: Evaluation of visual acuity changes may be more difficult in patients with cataracts, optic neuritis, diabetic retinopathy, and inflammatory conditions of the eye; consideration should be given to whether or not visual changes are related to disease progression or effects of therapy.

• Renal impairment: Use with caution in patients with renal impairment; dosage modification recommended. Monitor renal function prior to and during treatment.

Special populations:

• Pediatrics: Use only in children whose visual acuity can accurately be determined and monitored (not recommended for use in children <13 years of age unless the benefit outweighs the risk).

Adverse Reactions

Frequency not defined.

Cardiovascular: Myocarditis, pericarditis

Central nervous system: Confusion, disorientation, dizziness, fever, hallucinations, headache, malaise

Dermatologic: Dermatitis, erythema multiforme, exfoliative dermatitis, pruritus, rash

Endocrine & metabolic: Acute gout or hyperuricemia

Gastrointestinal: Abdominal pain, anorexia, GI upset, nausea, vomiting

Hematologic: Eosinophilia, leukopenia, lymphadenopathy, neutropenia, thrombocytopenia

Hepatic: Hepatitis, hepatotoxicity (possibly related to concurrent therapy), LFTs abnormal

Neuromuscular & skeletal: Arthralgia, peripheral neuritis

Ocular: Optic neuritis; symptoms may include decreased acuity, scotoma, color blindness, or visual defects (usually reversible with discontinuation, irreversible blindness has been described)

Renal: Nephritis

Respiratory: Infiltrates (with or without eosinophilia), pneumonitis

Miscellaneous: Anaphylaxis, anaphylactoid reaction; hypersensitivity syndrome (cutaneous reactions, eosinophilia, and organ-specific inflammation)

Metabolism/Transport Effects

None known.

Drug Interactions

Aluminum Hydroxide: May decrease the absorption of Ethambutol. Risk D: Consider therapy modification

Storage

Store at controlled room temperature of 20°C to 25°C (68°F to 77°F).

Mechanism of Action

Inhibits arabinosyl transferase resulting in impaired mycobacterial cell wall synthesis

Pharmacodynamics/Kinetics

Absorption: ~80%

Distribution: Widely throughout body; concentrated in kidneys, lungs, saliva, and red blood cells

Relative diffusion from blood into CSF: Adequate with or without inflammation (exceeds usual MICs)

CSF:blood level ratio: Normal meninges: 0%; Inflamed meninges: 25%

Protein binding: 20% to 30%

Metabolism: Hepatic (20%) to inactive metabolite

Half-life elimination: 2.5-3.6 hours; End-stage renal disease: 7-15 hours

Time to peak, serum: 2-4 hours

Excretion: Urine (~50% as unchanged drug, 8% to 15% as metabolites); feces (~20% as unchanged drug)

Dosage

Usual dosage range: Oral:

Children: 15-20 mg/kg/day (maximum: 1 g/day) or 50 mg/kg/dose twice weekly (maximum: 2.5 g/dose)

Adults: 15-25 mg/kg daily (maximum dose: 1.5-2.5 g) or 25-30 mg/kg/dose 3 times/week (maximum: 2.4 g/dose) or 50 mg/kg/dose twice weekly (maximum: 4 g/dose)

Indication-specific dosing: Oral:

Infants and Children:

Mycobacterium avium (MAC), secondary prophylaxis or treatment: HIV-exposed/-infected: 15-25 mg/kg/day once daily (maximum: 2.5 g/day) with clarithromycin (or azithromycin) with or without rifabutin (CDC, 2009)

Children:

Tuberculosis, active: 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.

HIV negative: Daily therapy: 15-20 mg/kg/day (maximum: 1 g/day); Twice weekly directly observed therapy (DOT): 50 mg/kg (maximum: 2.5 g/dose) (MMWR, 2003)

HIV-exposed/-infected: Daily therapy: 15-25 mg/kg/day (maximum: 2.5 g/day) (CDC, 2009)

Adolescents ≥13 years:

Tuberculosis, active: Refer to adult dosing.

Adults:

Disseminated Mycobacterium avium (MAC) treatment in patients with advanced HIV infection (unlabeled use; ATS/IDSA guidelines, 2007): 15 mg/kg ethambutol in combination with clarithromycin or azithromycin with/without rifabutin

Nontuberculous mycobacterium (M. kansasii) (unlabeled use; ATS/IDSA guidelines, 2007): 15 mg/kg/day ethambutol for duration to include 12 months of culture-negative sputum; typically used in combination with rifampin and isoniazid; Note: Previous recommendations stated to use 25 mg/kg/day for the initial 2 months of therapy; however, IDSA guidelines state this may be unnecessary given the success of rifampin-based regimens with ethambutol 15 mg/kg/day or omitted altogether.

Tuberculosis, active: 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.

FDA-approved labeling: Adolescents ≥13 years and Adults: Initial: 15 mg/kg once daily (maximum dose: 1.5 g); Retreatment (previous antituberculosis therapy): 25 mg/kg once daily (maximum dose: 2.5 g) for 60 days or until bacteriologic smears and cultures become negative, followed by 15 mg/kg daily.

Suggested doses by lean body weight (CDC, 2003)

Daily therapy: 15-25 mg/kg (maximum dose: 1.6 g)

40-55 kg: 800 mg

56-75 kg: 1200 mg

76-90 kg: 1600 mg

Twice weekly directly observed therapy (DOT): 50 mg/kg (maximum dose: 4 g)

40-55 kg: 2000 mg

56-75 kg: 2800 mg

76-90 kg: 4000 mg

Three times/week DOT: 25-30 mg/kg (maximum dose: 2.4 g)

40-55 kg: 1200 mg

56-75 kg: 2000 mg

76-90 kg: 2400 mg

Dosing interval in renal impairment:

MMWR, 2003: Cl_cr <30 mL/minute and hemodialysis: 15-25 mg/kg/dose 3 times weekly

Aronoff, 2007

Cl_cr 10-50 mL/minute: Administer every 24-36 hours

Cl_cr <10 mL/minute: Administer every 48 hours

Hemodialysis: Slightly dialyzable (5% to 20%); Administer dose postdialysis

Peritoneal dialysis: Dose for Cl_cr <10 mL/minute: Administer every 48 hours

Continuous arteriovenous or venovenous hemofiltration: Dose for Cl_cr 10-50 mL/minute: Administer every 24-36 hours

Monitoring Parameters

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

Dietary Considerations

May be taken with food as absorption is not affected, may cause gastric irritation.

Patient Education

Take with meals. May cause GI distress, dizziness, disorientation, and drowsiness. You will need to have frequent ophthalmic exams and periodic medical check-ups to evaluate drug effects. Report vision changes, numbness or tingling of extremities, or persistent loss of appetite.

Geriatric Considerations

Since most elderly patients acquired their tuberculosis before current antituberculin regimens were available, ethambutol is only indicated when patients are from areas where drug resistant M. tuberculosis is endemic, in HIV-infected elderly patients, and when drug resistant M. tuberculosis is suspected (see dose adjustments for renal impairment).

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause confusion and disorientation

Mental Health: Effects on Psychiatric Treatment

None reported

Nursing: Physical Assessment/Monitoring

Use caution in presence of renal insufficiency. Assess results of visual tests at baseline and periodically throughout therapy. Monitor for CNS changes, neuritis, and ocular changes on a regular basis during therapy. Teach patient need to adhere to dosing program and importance of regular laboratory tests and ophthalmic evaluations.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral, as hydrochloride: 100 mg, 400 mg

Myambutol®: 100 mg

Myambutol®: 400 mg [scored]

Pricing: U.S. (www.drugstore.com)

Tablets (Ethambutol HCl)

400 mg (30): $52.99

References

Addis A, Blowey D, and Koren G, “Tuberculosis During Pregnancy,” Can Fam Physician, 1996, 42:1461-2.

American Academy of Pediatrics, Committee on Drugs, “Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.

American Academy of Pediatrics, Committee on Infectious Diseases, “Chemotherapy for Tuberculosis in Infants and Children,” Pediatrics, 1992, 89(1):161-5.

American Thoracic Society, “Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection,” MMWR Recomm Rep, 2000, 49(RR-6):1-51.

Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children, 5th ed. Philadelphia, PA: American College of Physicians; 2007.

Blumberg HM, Burman WJ, Chaisson RE, et al, “American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis,” Am J Respir Crit Care Med, 2003, 167(4):603-62.

Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf

Centers for Disease Control and Prevention, “Treatment of Tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society of America,” 2003,” MMWR Recomm Rep, 52(RR11):3-5.

Ducobu J, DuPont P, Laurent M, et al, “Acute Isoniazid/Ethambutol/Rifampicin Overdosage,” Lancet, 1982, 1(8272):632.

Griffith DE, Aksamit T, Brown-Elliott BA, et al, “An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases,” Am J Respir Crit Care Med, 2007, 175(4):367-416.

Havlir DV and Barnes PF, “Tuberculosis in Patients With Human Immunodeficiency Virus Infection,” N Engl J Med, 1999, 340(5):367-73.

“Prevention and Treatment of Tuberculosis Among Patients Infected With Human Immunodeficiency Virus: Principles of Therapy and Revised Recommendations. Centers for Disease Control and Prevention,” MMWR Recomm Rep, 1998, 47(RR-20):1-58.

Starke JR, “Multidrug Therapy for Tuberculosis in Children,” Pediatr Infect Dis J, 1990, 9(11):785-93.

Starke JR and Correa AG, “Management of Mycobacterial Infection and Disease in Children,” Pediatr Infect Dis J, 1995, 14(6):455-70.

Tran JH and Montakantikul P, “The Safety of Antituberculosis Medications During Breastfeeding,” J Hum Lact, 1998, 14(4):337-40.

“Treatment of Latent Tuberculosis Infection (LTBI), Last Updated: April 8, 2004.” Available at http://www.cdc.gov/nchstp/tb/pubs/tbfactsheets/250110.htm. Last accessed February 16, 2005.

Yoshikawa TT, “Tuberculosis in Aging Adults,” J Am Geriatr Soc, 1992, 40(2):178-87.

International Brand Names

• Ambutol (MY)
• Arbutol (ID)
• Bacbutol (ID)
• Clobutol (PT)
• Combutol (IN)
• Corsabutol (ID)
• Dexambutol (FR)
• Ebutol (TW)
• Ecox (CO)
• EMB (DE)
• EMB-Fatol (HK)
• Etambutol (BG, BR, HR)
• Etambutol Northia (AR)
• Etambutol Richet (AR)
• Etambutol Richmond (AR)
• Etapiam (IT)
• ETH Ciba 400 (ID)
• Etham (TH)
• Ethambin-PIN (PH)
• Ethambutol (PL)
• Ethbutol (TH)
• Etibi (AT, ID, IT)
• Interbutol (PH)
• Lambutol (TH)
• Manzida (MX)
• Myambutol (AT, AU, BE, BF, BJ, CH, CI, DE, DK, ES, ET, FR, GB, GH, GM, GN, GR, IE, IN, KE, KP, LR, LU, MA, ML, MR, MU, MW, MY, NE, NG, NL, NZ, PK, PT, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, ZM, ZW)
• Mycobutol (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW)
• Oributol (FI)
• Purderal (ZA)
• Servambutol (PE)
• Stambutol (FI)
• Sural (CZ, HN, HU)
• Tibigon (ID)
• Tibitol (ID, IN)
• Tibutol (PE)
• Tobutol (TH)

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Last full review/revision January 2012

Content last modified January 2012