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Ethambutol


General


Pronunciation

(e THAM byoo tole)


Brand Names: U.S.

  • Myambutol

Indications


Use: Labeled Indications

Treatment of pulmonary tuberculosis in conjunction with other antituberculosis agents


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


Dosing and Administration


Dosing: Adult

DisseminatedMycobacterium avium(MAC) treatment in patients with advanced HIV infection (off-label use; ATS/IDSA guidelines, 2007): Oral: 15 mg/kg ethambutol in combination with clarithromycin or azithromycin with/without rifabutin

Tuberculosis, active: Oral: FDA-approved labeling: Adolescents ≥13 years and Adults: Initial: 15 mg/kg once daily (maximum dose: 1.5 g); Re-treatment (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

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.

Nontuberculous mycobacterium (M. kansasii) (off-label use; ATS/IDSA guidelines, 2007): Oral: 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.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

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

Tuberculosis, active: Oral: 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:

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: Refer to adult dosing.


Dosing: Renal Impairment

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

Aronoff, 2007

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

CrCl <10 mL/minute: Administer every 48 hours

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

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

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


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturers labeling; use with caution.


Dietary Considerations

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


Storage

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


Dosage Forms/Strengths


Dosage Forms

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

Tablet, Oral, as hydrochloride:

Myambutol: 100 mg

Myambutol: 400 mg [scored]

Generic: 100 mg, 400 mg


Drug Interactions

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


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


Adverse Reactions


Frequency not defined.

Cardiovascular: Myocarditis, pericarditis

Central nervous system: Confusion, disorientation, dizziness, hallucination, headache, malaise, peripheral neuritis

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

Endocrine & metabolic: Acute gout attack, hyperuricemia

Gastrointestinal: Abdominal pain, anorexia, gastric distress, nausea, vomiting

Hematologic & oncologic: Eosinophilia, leukopenia, lymphadenopathy, neutropenia, thrombocytopenia

Hepatic: Abnormal hepatic function tests, hepatitis, hepatotoxicity (possibly related to concurrent therapy)

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

Neuromuscular & skeletal: Arthralgia

Ophthalmic: Color blindness, decreased visual acuity, optic neuritis, scotoma, visual disturbance (usually reversible with discontinuation; irreversible blindness has been described)

Renal: Nephritis

Respiratory: Pneumonitis, pulmonary infiltrates (with or without eosinophilia)

Miscellaneous: Fever


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:

- Pediatric: 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).


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.


Actions


Pharmacology

Inhibits arabinosyl transferase resulting in impaired mycobacterial cell wall synthesis


Absorption

~80%


Distribution

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

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


Metabolism

Hepatic (20%) to inactive metabolite


Excretion

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


Time to Peak

Serum: 2-4 hours


Half-Life Elimination

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


Protein Binding

20% to 30%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience nausea, vomiting, lack of appetite, dizziness, headache, or abdominal pain. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), confusion, hallucinations, joint pain, joint edema, numbness or tingling of hands or feet, bruising, bleeding, or vision changes (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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