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Medication Safety Issues

Sound-alike/look-alike issues:

Myambutol® may be confused with Nembutal®

Pronunciation

(e THAM byoo tole)

U.S. Brand Names

• Myambutol®

Index Terms

• Ethambutol Hydrochloride

Generic Available

Yes

Canadian Brand Names

• Etibi®

Pharmacologic Category

• Antitubercular Agent

Pharmacologic Category Synonyms

• Tuberculosis Treatment Agent

Use: Labeled Indications

Treatment of tuberculosis and other mycobacterial diseases in conjunction with other antituberculosis agents

Pregnancy Risk Factor

C

Pregnancy Considerations

There are no adequate and well-controlled studies in pregnant women; teratogenic effects have been seen in animals. Ethambutol has been used safely during pregnancy.

Lactation

Enters breast milk/use caution (AAP considers “compatible”)

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; use in 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.

• Optic neuritis: May cause optic neuritis, 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).

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage modification recommended.

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: Headache, confusion, disorientation, malaise, mental confusion, fever, dizziness, hallucinations

Dermatologic: Rash, pruritus, dermatitis, exfoliative dermatitis

Endocrine & metabolic: Acute gout or hyperuricemia

Gastrointestinal: Abdominal pain, anorexia, nausea, vomiting

Hematologic: Leukopenia, thrombocytopenia, eosinophilia, neutropenia, lymphadenopathy

Hepatic: Abnormal LFTs, hepatotoxicity (possibly related to concurrent therapy), hepatitis

Neuromuscular & skeletal: Peripheral neuritis, arthralgia

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 (rash, eosinophilia, and organ-specific inflammation)

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

Suppresses mycobacteria multiplication by interfering with RNA 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%) and 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: 4 g/dose)

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

Indication-specific dosing: Oral:

Disseminated Mycobacterium avium complex (MAC) in patients with advanced HIV infection: Adults: 15 mg/kg ethambutol in combination with azithromycin 600 mg daily

Nontuberculous mycobacterium ( M. kansasii ) (unlabeled use; IDSA guidelines): Adults: 15 mg/kg/day 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.

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)

Dosing interval in renal impairment:

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

Continuous arteriovenous or venovenous hemofiltration: 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 as scheduled, with meals. Avoid missing doses and do not discontinue without consulting prescriber. Avoid aluminum-containing antacids for at least 4 hours following ethambutol. May cause GI distress (small, frequent meals and good oral care may help), dizziness, disorientation, drowsiness (avoid driving or engaging in tasks that require alertness until response to drug is known). 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. Pregnancy precaution: Inform prescriber if you are or intend to become pregnant.

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 baseline and periodic laboratory tests, therapeutic effectiveness, and adverse response (eg, CNS changes, neuritis, and ocular changes) on a regular basis during therapy. Teach patient appropriate use (need to adhere to dosing program), possible side effects/appropriate interventions (regular ophthalmic evaluations), and adverse symptoms to report.

Dosage Forms

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

Tablet, as hydrochloride: 100 mg, 400 mg

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

Tablets (Ethambutol HCl)

400 mg (30): $55.99

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, “The 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.

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 (CDC) and American Thoracic Society, “Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection - United States, 2003,” MMWR, 2003, 52(31):735-9. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm. Last accessed February 16, 2005.

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);62-3.

Citron KM and Thomas GO, “Ocular Toxicity From Ethambutol,” Thorax, 1986, 41(10):737-9.

Davidson PT and Le HQ, “Drug Treatment of Tuberculosis - 1992,” Drugs, 1992, 43(5):651-73.

“Drugs for Tuberculosis,” Med Lett Drugs Ther, 1993, 35(908):99-101.

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.

Iseman MD, “Treatment of Multidrug-Resistant Tuberculosis,” N Engl J Med, 1993, 329(11):784-91.

Karnik AM, Al-Shamali MA, and Fenech FF, “A Case of Ocular Toxicity to Ethambutol - An Idiosyncratic Reaction?” Postgrad Med J, 1985, 61(719):811-3.

“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.

Van Scoy RE and Wilkowske CJ, “Antituberculous Agents,” Mayo Clin Proc, 1992, 67(2):179-87.

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

International Brand Names

• Althocin (GR)
• Ambutol (MY)
• Arbutol (ID)
• Bacbutol (ID)
• Blomison (GR)
• Clobutol (PT)
• Combutol (IN)
• Corsabutol (ID)
• Dexambutol (FR)
• Ebutol (TW)
• 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, PK, PT, SC, SD, SE, SL, SN, TH, TN, TW, TZ, UG, ZA, 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, ZA, ZM, ZW)
• Odetol (PH)
• Oributol (FI)
• Purderal (ZA)
• Servambutol (PE)
• Stambutol (FI)
• Sural (CZ, HN, HU)
• Tibigon (ID)
• Tibitol (ID, IN)
• Tibutol (PE)
• Tobutol (TH)

Lexi-Comp.com

Last full review/revision August 2008

Content last modified August 2008