ETHAMBUTOL

CASRN: 74-55-5

For other data, click on the Table of Contents

Human Health Effects:

Toxicity Summary: IDENTIFICATION: Ethambutol is used to treat tuberculosis. Ethambutol is an odorless crystalline hygroscopic powder. It is soluble in water, alcohol, chloroform, methyl alcohol, and very slightly soluble in ether. HUMAN EXPOSURE: Summary: Main risks and target organs: During chronic treatment ethambutol may produce visual and neurological disturbances, allergic reactions, gastrointestinal symptoms, psychiatric symptoms and transient impairment of liver function. This last event has a very low incidence. Increased serum uric acid levels and acute gouty arthritis have been reported. Summary of clinical effects: Acute overdosage may cause gastrointestinal symptoms, hallucinations and optic neuritis. Acute overdosage symptoms include nausea, abdominal pain, fever, mental confusion, visual hallucinations, and optic neuropathy (retrobulbar neuritis) with doses over 10 g. The effects of overdosage are not well established. During chronic treatment the following have been reported: Visual disturbances: Ethambutol may produce a reduction of visual acuity which appear to be due to optic neuritis. Central scotoma and green-red colour blindness may also occur. Allergic reactions: Rash, anaphylactoid reactions, dermatitis and pruritus. Gastrointestinal symptoms: Abdominal pain, anorexia, nausea, vomiting. Neurological disturbances and psychiatric symptoms: Headache, peripheral neuritis, dizziness, mental confusion, disorientation and hallucinations. Other side effects: Jaundice, transient impairment of liver function, fever, increase of serum uric acid levels, joint pain, acute gouty arthritis, malaise. Ethambutol may diffuse into milk. Ethambutol is a synthetic oral antibiotic derivative of ethylenediamine. Contraindications: Ethambutol hydrochloride is contraindicated in patients who are known to be hypersensitive to this drug. Renal impairment, old age and optic neuritis are relative contraindications. Routes of entry: Oral: Ethambutol is only available for oral use. Absorption by route of exposure: About 80% of an oral dose of ethambutol is absorbed from the gastro-intestinal tract, and the remainder appears in the feces unchanged. Absorption is not significantly impaired by food. Distribution by route of exposure: Ethambutol diffuses readily into red blood cells and into the cerebrospinal fluid when the meninges are inflamed. The concentration in erythrocytes at steady state is approximately twice the plasma concentration. It has been reported to cross the placenta and is excreted in breast milk. Biological half-life by route of exposure: The serum half-life in therapeutic doses is 3 hours, increasing in renal failure, as 80% is excreted renally. Metabolism: The main path of metabolism appears to be an initial oxidation of the alcohol to an aldehydic intermediate, followed by conversion to a dicarboxylic acid. Elimination by route of exposure: During the 24 hour period following oral administration of ethambutol, approximately 50% of the initial dose is excreted unchanged in the urine, while an additional 8% to 15% appears in the form of metabolites. From 20 to 22% of the initial dose is excreted in the feces as unchanged drug. Mode of action: Toxicodynamics: The underlying cause of visual alterations appears to be a disturbance of metabolism due to depletion of copper and zinc which

serve as prosthetic groups for many enzymes. The eye normally contains a considerable store of zinc. Much of the zinc is in the pigmented cells of the outer zone of the retina, where it serves as a metal prosthetic group for retinol (alcohol) dehydrogenase. Pharmacodynamics: Ethambutol is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis. Ethambutol is bacteriostatic and appears to inhibit the synthesis of one or more metabolites, thus causing impairment of cell metabolism, arrest of multiplication, and cell death. No cross resistance with other available antimycobacterial agents has been demonstrated. Ethambutol has been shown to be effective against strains of mycobacterium tuberculosis but does not seem to be active against fungi, viruses, or other bacteria. Ethambutol is also active against some atypical mycobacteria including M. kansasii. Primary resistance to ethambutol is uncommon in developed countries but resistant strains of M. tuberculosis are readily produced if the drug is used alone. Human data: Adults: Subclinical impairment of colour discrimination was reported to be relatively common in patients receiving ethambutol daily as part of antituberculous chemotherapy when compared with 50 patients receiving other antituberculous agents. Peripheral neuropathy has been reported in tubercular patients who had received ethambutol among other drugs. Interactions: Results of a crossover study involving 13 tuberculous patients suggest that concomitant administration of aluminium hydroxide may delay and reduce absorption of ethambutol in some patients. Untoward effects may be enhanced when ethambutol is combined with isoniazid or rifampicin. Main adverse effects: Ethambutol may produce decreased visual acuity which appear to be due to optic neuritis and to be related to dose and duration of treatment. The effects are generally reversible when administration of the drug is discontinued promptly. Ethambutol may produce constriction of visual field, central and peripheral scotoma, and green-red color blindness which may be associated with retrobulbar neuritis. Renal clearance of urate may be reduced in about 50% of patients receiving ethambutol and acute gout has been precipitated in patients with gout or impaired renal function. Cholestatic jaundice has been reported. ANIMAL/PLANT STUDIES: Relevant animal data: Toxicological studies in dogs on high prolonged doses, produced evidence of myocardial damage and failure, and depigmentation of the tapetum lucidum of the eyes, the significance of which is not known. Degenerative changes in the central nervous system, apparently not dose-related, have also been noted in dogs receiving ethambutol hydrochloride over a prolonged period. In the rhesus monkey, neurological signs appeared after treatment with high doses given daily over a period of several months. These correlated with specific serum levels of ethambutol hydrochloride and with definite neuro-anatomical changes in the central nervous system. Focal interstitial carditis was also noted in monkeys which received ethambutol hydrochloride in high doses for a prolonged period.
[International Programme on Chemical Safety; Poisons Information Monograph: Ethambutol (PIM 218) (1990) Available from, as of May 19, 2005: http://www.inchem.org/pages/pims.html **PEER REVIEWED**

Human Toxicity Excerpts: /HUMAN EXPOSURE STUDIES/ The aim of the present study was to describe the side effects related to combined Pyrazinamide (PZA) and ethambutol (EMB) treatment given for LTBI, in contacts previously exposed to MDR-TB. In total, 12 consecutive contacts, all of African origin and aged 38+/-5 yrs, were treated with daily PZA (23+/-4 mg.kg(-1)) and EMB (17+/-4 mg.kg(-1)) at Geneva University Hospital outpatient clinic (Switzerland), as a result of contact-tracing procedures for two patients with contagious MDR-TB. Clinical status and liver function tests (aspartate aminotransferase (ALAT) and alanine aminotransferase (ASAT)) were monitored monthly. In seven cases (58%) treatment was discontinued after a median of 119 days, due to hepatic toxicity in six cases (ALAT or ASAT elevation more than four times the upper normal limit), and gastrointestinal symptoms in one case.
[Younossian A et al; Eur Respir J 26 (3): 462-4 (2005)] **PEER REVIEWED** PubMed Abstract

/HUMAN EXPOSURE STUDIES/ Seventy patients with pulmonary tuberculosis and 12 healthy controls were included in a study to observe the effect of ethambutol on serum uric acid level. In ethambutol-treated cases a statistically significant increase in mean serum uric acid levels was

observed in the second, third and fourth week of treatment. This increase was independent of dosage of ethambutol. However, 22 of the 52 (42%) ethambutol-treated cases showed no increase. ... Hyperuricemia due to ethambutol was reversed with probenecid but not by salicylates. No patient developed acute gouty arthritis although two developed arthralgia.
[Narang RK et al; Br J Dis Chest 77 (4): 403-6 (1983)] **PEER REVIEWED** PubMed Abstract

/EPIDEMIOLOGY STUDIES/ A retrospective observational case series from a single neuroophthalmology practice. 8 patients with a history of ethambutol-induced optic neuropathy were examined within 3 months after stopping ethambutol treatment. All patients underwent a neuroophthalmologic examination, including visual acuity, color vision, visual fields and funduscopy. Optical coherence tomography (OCT) was performed on both eyes of each patient using the retinal nerve fibre layer analysis protocol. The interval between cessation of ethambutol treatment and the initial visit ranged from 1 week to 3 months. All patients had visual deficits characteristic of ethambutol-induced optic neuropathy at their initial visit, and the follow-up examination was performed within 12 months. Compared with the initial retinal nerve fibre layer thickness (RNFLT), there was a statistically significant decrease in the mean RNFLT of the temporal, superior and nasal quadrants (p = 0.009, 0.019 and 0.025, respectively), with the greatest decrease in the temporal quadrant (mean decrease 26.5 mum). A decrease in RNFLT is observed in all quadrants in patients with ethambutol-induced optic neuropathy who have recently discontinued the medication. This decrease is most pronounced in the temporal quadrant of the optic disc.
[Chai S, Foroozan R; Br J Ophthalmol 91 (7): 895-7 (2007)] **PEER REVIEWED** PubMed Abstract

/HUMAN EXPOSURE STUDIES/ From January 1984-December 1987, 1783 patients received combination therapy of isoniazid, rifampin, and ethambutol for the control of tuberculosis. Fortytwo developed symptomatic hepatitis during the period of treatment. Fifteen were hepatitis B virus carriers, and the remaining 27 were noncarriers. The peak serum transaminase and bilirubin levels were higher in carriers. Seven carriers died of fulminant or subacute hepatic failure, and only 1 noncarrier died. Eleven carriers had detectable serum hepatitis B virus deoxyribonucleic acid during the acute stage of hepatitis.
[Wu JC et al; Gastroenterology 98 (2): 502-4 (1990)] **PEER REVIEWED** PubMed Abstract

/SIGNS AND SYMPTOMS/ The most important adverse effect of ethambutol is optic neuritis with decreases in visual acuity, constriction of visual fields, central and peripheral scotomas, and loss of red-green color discrimination. The extent of ocular toxicity appears to be related to the dose and duration of ethambutol therapy. However, such toxicity also has been reported rarely after only a few days of therapy with the drug, and may represent an idiosyncratic reaction.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

/CASE REPORTS/ /Investigators/ report a case of an elderly male whose pulmonary reaction with skin eruption occurred in the initial phase of chemotherapy composed of isoniazid, rifampicin, and ethambutol (EB). A peripheral lymphocyte stimulation test (LST) showed a positive reaction only to EB. The blood serum analysis of the patient when this reaction occurred revealed an elevated titer of antinuclear antibody. Computed tomography (CT) scan films of the chest when the pulmonary reaction occurred showed multifocal subpleural consolidations. There has been only one reported case of EB-induced pulmonary reaction and its clinical course was very similar to /the one described herein/.
[Hiraoka K et al; J UOEH 20 (2): 145-51 (1998)] **PEER REVIEWED** PubMed Abstract

/CASE REPORTS/ A 67 year old woman presented with miliary tuberculosis. She was treated with streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide. However, she developed rifampicin-induced thrombocytopenia after 6 weeks of treatment, and skin rash, blood eosinophilia and pulmonary infiltrates after 8 weeks of therapy. The latter was found to be ethambutol related. Additional evidence, including blood and sputum eosinophilia and the rapidity of its response to corticosteroid, suggested that the pulmonary infiltrates might also be eosinophilic in nature.
[Wong P et al; Eur Respir J 8 (5): 866-8 (1995)] **PEER REVIEWED** PubMed Abstract

/CASE REPORTS/ A 55-year-old man presented with the suspicion of pulmonary tuberculosis. He was treated with isoniazid, ethambutol, rifampicin and pyrazinamide. However, he developed high fever, skin rash and pulmonary infiltrates following 10 days of treatment. The above-mentioned conditions subsided promptly after stopping ethambutol therapy and reappeared after rechallenge, marking ethambutol as the offender.
[Chien H et al; Zhonghua Yi Xue Za Zhi (Taipei) 61 (6): 371-4 (1998)] **PEER REVIEWED** PubMed Abstract

/CASE REPORTS/ A woman developed peripheral neuropathy and optic neuritis while receiving ethambutol in the retreatment of drug-resistant pulmonary tuberculosis. There was prompt improvement in peripheral neuropathy and the ocular symptoms following the withdrawal of the drug.
[Nair V et al; Chest 77 (1): 98-100 (1980)] **PEER REVIEWED** PubMed Abstract

/CASE REPORTS/ A 10-year-old girl with cervical tuberculosis was treated with Isoniazid, Rimfampicin and Ethambutol. After 2 weeks of treatment a hepatotoxic reaction developed. Withdrawal of therapy resulted in complete clinical improvement and in normalization of all laboratory measurements. Treatment was restarted with Rifampicin, Pyrazinamid and Ethambutol. Liver enzyme levels were monitored weekly. Seven weeks after this three-drug regiment was started, all therapy was discontinued because of elevated liver enzyme levels. However, the patient died 2 weeks later of progressive fulminant hepatitis.
[van Aalderen WM et al; Eur J Pediatr 146 (3): 290-1(1987)] **PEER REVIEWED** PubMed Abstract

/CASE REPORTS/ /The authors/ report the case of a 51-year-old man with suspected tuberculosis (TB) pleurisy. An anti-TB trial with INH, rifampicin and ethambutol (EMB) was given initially. Dizziness, disorientation, and auditory and visual hallucinations developed after seven days of therapy. Laboratory examinations, including routine biochemistry tests, serum titer of antinuclear antibodies, cerebrospinal fluid analysis and computerized tomography of the head showed no abnormal findings. Following discontinuation of anti-TB agents, the psychiatric symptoms subsided. When the patient was challenged with EMB, the same psychiatric symptoms recurred, but resolved again after discontinuation of EMB.
[Hsu CW et al; Zhonghua Yi Xue Za Zhi (Taipei) 62 (10): 724-7 (1999)] **PEER REVIEWED** PubMed Abstract

/CASE REPORTS/ Two patients with bilateral visual loss due to ethambutol toxicity underwent mfERG testing that disclosed both diffuse and central field loss compatible with retinal dysfunction as a contributing mechanism to the visual field loss. Ethambutol toxicity affects not only the optic nerve but probably other retinal elements based upon abnormal mfERG findings.
[Kardon R et al; Semin Ophthalmol 21 (4): 215-22 (2006)] **PEER REVIEWED** PubMed Abstract

Drug Warnings: Appropriate studies on the relationship of age to the effects of ethambutol have not been performed in children up to 13 years of age. Ethambutol is generally not recommended in children whose visual acuity cannot be monitored (younger than 6 years of age). However, ethambutol should be considered for all children with organisms resistant to other medications, and in whom susceptibility to ethambutol has been demonstrated or is likely.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1335] **PEER REVIEWED**

The most important adverse effect of ethambutol is optic neuritis with decreases in visual acuity, constriction of visual fields, central and peripheral scotomas, and loss of red-green color discrimination. The extent of ocular toxicity appears to be related to the dose and duration of ethambutol therapy. However, such toxicity also has been reported rarely after only a few days of therapy with the drug, and may represent an idiosyncratic reaction.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of

Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

Other adverse effects of ethambutol include dermatitis, pruritus, headache, malaise, dizziness, fever, mental confusion, disorientation, possible hallucinations, joint pain, and rarely anaphylactoid reactions. GI upset, abdominal pain, nausea, vomiting, and anorexia have also occurred occasionally with ethambutol. Peripheral neuritis, with numbness and tingling of the extremities, has been reported infrequently. Increased serum uric acid concentrations and precipitation of acute gout have occurred occasionally in patients receiving ethambutol and are probably the result of decreased renal clearance of urate. Transient impairment of liver function, as indicated by abnormal liver function test results, has also occurred. Cholestatic jaundice, which appeared to be caused by ethambutol, has been reported in at least one patient who received the drug both alone and in conjunction with streptomycin.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

Visual testing should be performed prior to initiating ethambutol therapy and then periodically during therapy with the drug. Testing should be done monthly in patients receiving more than 15 mg/kg daily. Examinations should include ophthalmoscopy, finger perimetry, and testing of color discrimination. Patients developing adverse ocular effects during ethambutol therapy may show subjective visual symptoms either before or simultaneously with decreases in visual acuity. All patients receiving the drug should be questioned periodically about blurred vision and other subjective visual symptoms and should be instructed to report to their physicians any such changes as soon as they are noticed. If substantial changes in visual acuity occur, ethambutol should be discontinued immediately.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

The manufacturer states that ethambutol should not be used in children younger than 13 years of age. The American Thoracic Society (ATS), US Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) state that ethambutol should be used with caution in children in whom it may be difficult to monitor visual acuity (e.g., those younger than 5 years of age). These experts state that ethambutol usually is recommended for use in such children only when the strain of Mycobacterium tuberculosis involved is known or suspected to be resistant to isoniazid or rifampin or when the child has adult-type (upper lobe infiltration, cavity formation) tuberculosis.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

Renal, hepatic, and hematopoietic tests should be performed periodically during long-term ethambutol therapy.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

Ethambutol is contraindicated in patients with optic neuritis unless clinical judgment deems it necessary that the drug be used. Ethambutol is also contraindicated in patients with known hypersensitivity to the drug.
[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 551] **PEER REVIEWED**

Serum uric acid concentrations may be required during treatment since elevated serum uric acid concentrations frequently occur, possibly precipitating acute gout. Chills, pain and swelling of joints-especially big toe, ankle or knee; tense, hot skin over affected joints indicate need for medical attention.
[Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 1336] **PEER REVIEWED**

Maternal Medication usually Compatible with Breast-Feeding: Ethambutol: Reported Sign or

Symptom in Infant or Effect on Lactation: None. /from Table 6/

[Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1): 141 (1994)] **PEER REVIEWED**

Tuberculosis is neither more frequent, nor more serious in pregnant than non-pregnant women. The risks for the child are threefold: a doubling in the mortality level on account of the illness in the mother if she is not treated; a risk of toxicity linked to the anti-tuberculous drugs and a risk of tuberculous infection at birth. Isoniazid and ethambutol have a weak toxicity. These two antibiotics can be prescribed during pregnancy (after confirming the absence of Vitamin B6 deficiency in the mother). The treatment of tuberculosis in pregnancy will be rifampicin + isoniazid + ethambutol (the ethambutol being stopped after two months and the isoniazid and rifampicin after 9 mo of treatment). At the moment of confinement, if maternal tuberculosis is confirmed bacteriologically at the time of microscopy, chemoprophylaxis will be started in the new born with isoniazid, until the mother is bacteriologically negative on microscopic examination, the new born should then be vaccinated with BCG. If the treatment of the mother is correctly prescribed and followed breast feeding is possible and no isolation of either mother or child is necessary. The amt of antibiotic that passes in the mothers milk is minimal and such specific nourishment should not be dispensed with if the treatment is necessary.
[Dautzenberg B, Grosset J; Rev Mal Respir 5 (3): 279-83 (1988)] **PEER REVIEWED** PubMed Abstract

Etambutol CASRN: 74-55-5

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Efek Kesehatan Manusia:

Toksisitas Ringkasan: IDENTIFIKASI: Etambutol digunakan untuk mengobati tuberkulosis. Etambutol merupakan bubuk higroskopis berbau kristal. Hal ini larut dalam air, alkohol, kloroform, metil alkohol, dan sangat sedikit larut dalam eter. MANUSIA SAMBUNGAN: Ringkasan: risiko utama dan organ sasaran: Selama etambutol pengobatan kronis dapat menghasilkan gangguan visual dan neurologis, reaksi alergi, gejala gastrointestinal, gejala kejiwaan dan gangguan sementara fungsi hati. Acara terakhir ini memiliki insiden yang sangat rendah. Peningkatan kadar asam urat serum dan arthritis gout akut telah dilaporkan. Ringkasan efek klinis: overdosis akut dapat menyebabkan gejala gastrointestinal, halusinasi dan neuritis optik. Gejala overdosis akut termasuk mual, sakit perut, demam, kebingungan mental, halusinasi visual, dan neuropati optik (neuritis retrobulbar) dengan dosis lebih dari 10 g. Efek dari overdosis tidak mapan. Selama perawatan kronis berikut telah dilaporkan: Gangguan visual: Etambutol dapat menghasilkan pengurangan ketajaman visual yang tampaknya karena neuritis optik. Central scotoma dan buta warna hijau-merah juga dapat terjadi. Reaksi alergi: Ruam, anaphylactoid, dermatitis dan pruritus. Gejala gastrointestinal: nyeri perut, anoreksia, mual, muntah. Gangguan neurologis dan gejala kejiwaan: Sakit kepala, neuritis perifer, pusing, kebingungan mental, disorientasi dan halusinasi. Efek samping lain: Kuning, penurunan sementara fungsi hati, demam, peningkatan kadar serum asam urat, nyeri sendi, arthritis gout akut, malaise. Etambutol dapat berdifusi ke dalam susu. Etambutol merupakan turunan antibiotik oral sintetis etilendiamin. Kontraindikasi: hidroklorida Etambutol merupakan kontraindikasi pada pasien yang diketahui hipersensitif terhadap obat ini. Gangguan ginjal, usia tua dan optik neuritis merupakan kontraindikasi relatif. Rute masuk: Oral: Etambutol hanya tersedia untuk penggunaan oral. Penyerapan oleh jalur pemaparan: Sekitar 80% dari dosis oral etambutol diserap dari saluran pencernaan, dan

sisanya muncul dalam tinja berubah. Penyerapan tidak signifikan terganggu oleh makanan. Distribusi oleh jalur pemaparan: berdifusi Etambutol mudah ke dalam sel darah merah dan ke dalam cairan cerebrospinal ketika meninges meradang. Konsentrasi eritrosit pada steady state adalah sekitar dua kali konsentrasi plasma. Telah dilaporkan melewati plasenta dan diekskresikan dalam ASI. Biologi paruh oleh jalur pemaparan: paruh serum dalam dosis terapi adalah 3 jam, meningkat pada gagal ginjal, 80% diekskresikan melalui ginjal. Metabolisme: Jalur utama metabolisme tampaknya menjadi oksidasi awal alkohol ke aldehydic menengah, diikuti oleh konversi ke asam dikarboksilat. Eliminasi oleh jalur pemaparan: Selama periode 24 jam setelah pemberian oral etambutol, sekitar 50% dari dosis awal diekskresikan tidak berubah dalam urin, sementara tambahan 8% sampai 15% muncul dalam bentuk metabolit. Dari 20 sampai 22% dari dosis awal diekskresikan dalam tinja sebagai obat tidak berubah. Modus tindakan: Toxicodynamics: Penyebab yang mendasari perubahan visual yang tampaknya menjadi gangguan metabolisme akibat penipisan tembaga dan seng yang berfungsi sebagai kelompok prostetik bagi banyak enzim. Mata biasanya mengandung sebuah toko besar seng. Sebagian besar seng berada dalam sel-sel berpigmen dari zona luar retina, di mana ia berfungsi sebagai kelompok prostetik logam untuk retinol (alkohol) dehidrogenase. Farmakodinamik: Etambutol adalah agen kemoterapi lisan yang secara khusus efektif terhadap aktif tumbuh mikroorganisme dari genus Mycobacterium, termasuk M. tuberculosis. Etambutol adalah bakteriostatik dan tampaknya menghambat sintesis satu atau lebih metabolit, sehingga menyebabkan gangguan metabolisme sel, penangkapan perkalian, dan kematian sel. Tidak ada resistensi silang dengan agen antimikroba lain yang tersedia telah dibuktikan. Etambutol telah terbukti efektif terhadap strain tuberkulosis mycobacterium tapi sepertinya tidak untuk menjadi aktif terhadap jamur, virus, atau bakteri lainnya. Etambutol juga aktif terhadap beberapa mikobakteri atipikal termasuk M. kansasii. Resistensi utama untuk etambutol jarang di negara maju, tetapi strain yang resisten terhadap M. tuberculosis dapat segera diproduksi jika obat digunakan sendiri. Data Manusia: Dewasa: gangguan subklinis diskriminasi warna dilaporkan relatif umum pada pasien yang menerima etambutol setiap hari sebagai bagian dari kemoterapi antituberkulosis bila dibandingkan dengan 50 pasien yang menerima agen antituberkulosis lainnya. Neuropati perifer telah dilaporkan pada pasien TBC yang telah menerima etambutol antara obat lain. Interaksi: Hasil dari studi crossover yang melibatkan 13 pasien TB menunjukkan bahwa pemberian bersamaan aluminium hidroksida dapat menunda dan mengurangi penyerapan etambutol pada beberapa pasien. Efek yang tak diinginkan dapat ditingkatkan ketika etambutol dikombinasikan dengan isoniazid atau rifampicin. Main efek samping: Etambutol dapat menghasilkan penurunan ketajaman visual yang tampaknya karena neuritis optik dan berhubungan dengan dosis dan durasi pengobatan. Efek umumnya reversibel bila pemberian obat dihentikan segera. Etambutol dapat menghasilkan penyempitan bidang visual, skotoma sentral dan perifer, dan buta warna hijau-merah yang mungkin berhubungan dengan neuritis retrobulbar. Pembersihan ginjal urat dapat dikurangi dalam sekitar 50% dari pasien yang menerima etambutol dan akut gout telah diendapkan pada pasien dengan gout atau gangguan fungsi ginjal. Kolestasis jaundice telah dilaporkan. HEWAN / TANAMAN STUDI: data hewan yang relevan: studi Toksikologi pada anjing pada dosis tinggi berkepanjangan, bukti yang dihasilkan dari kerusakan miokard dan kegagalan, dan depigmentasi tapetum lucidum dari dari mata, signifikansi yang tidak diketahui. Perubahan degeneratif pada sistem saraf pusat, ternyata tidak berhubungan dengan dosis, juga telah dicatat pada anjing menerima hidroklorida etambutol selama jangka waktu lama. Dalam monyet rhesus, tanda-tanda neurologis muncul setelah pengobatan dengan dosis tinggi diberikan setiap hari selama beberapa bulan. Ini berkorelasi dengan tingkat serum spesifik hidroklorida ethambutol dan dengan pasti perubahan neuro-anatomi dalam sistem saraf pusat. Carditis interstitial focal juga dicatat pada monyet yang menerima etambutol hidroklorida dalam dosis tinggi dalam waktu lama. [International Programme on Chemical Safety, Racun Informasi Monografi: Etambutol (PIM 218) (1990) Tersedia dari, 19 Mei 2005: http://www.inchem.org/pages/pims.html ** PEER DITINJAU **

Toksisitas Kutipan Manusia: / MANUSIA SAMBUNGAN STUDIES / Tujuan dari penelitian ini adalah untuk menggambarkan efek samping yang berkaitan dengan gabungan Pyrazinamide (PZA) dan etambutol (EMB) pengobatan yang diberikan untuk LTBI, dalam kontak sebelumnya terkena MDR-TB. Secara total, 12 kontak berturut-turut, semua asal Afrika dan berusia 38 + / -5 thn, diobati dengan harian PZA (23 + mg.kg / -4 (-1)) dan EMB (17 + / -4 mg.kg (-1)) di Jenewa University Hospital klinik rawat jalan (Swiss), sebagai hasil dari prosedur melacak kontak untuk dua pasien dengan menular TB-MDR. Status klinis dan tes fungsi hati (aspartat aminotransferase (ALAT) dan alanine aminotransferase (ASAT)) dimonitor setiap bulan. Dalam tujuh kasus (58%) pengobatan dihentikan setelah median 119 hari, karena toksisitas hati dalam enam kasus (ALAT atau elevasi ASAT lebih dari empat kali batas normal atas), dan gejala gastrointestinal dalam satu kasus. [Younossian A et al, Eur Pernafasan J 26 (3): 462-4 (2005)] ** peer review ** PubMed Abstrak

/ SAMBUNGAN MANUSIA STUDI / Tujuh puluh pasien dengan TB paru dan 12 kontrol yang sehat dilibatkan dalam penelitian untuk mengamati pengaruh etambutol pada kadar asam urat serum. Dalam kasus etambutol diobati peningkatan signifikan secara statistik pada kadar asam urat serum rata-rata diamati pada minggu kedua, ketiga dan keempat pengobatan. Peningkatan ini tidak tergantung dosis ethambutol. Namun, 22 kasus etambutol yang diobati 52 (42%) tidak menunjukkan peningkatan. ... Hiperurisemia karena etambutol terbalik dengan probenesid tetapi tidak oleh salisilat. Tidak ada pasien mengalami arthritis gout akut meskipun dua dikembangkan arthralgia. [Narang RK et al, Br J Dis Dada 77 (4): 403-6 (1983)] ** peer review ** PubMed Abstrak

/ EPIDEMIOLOGI STUDI / Serangkaian kasus observasional retrospektif dari satu praktek neuro-oftalmologi. 8 pasien dengan riwayat neuropati optik etambutol-induced diperiksa dalam waktu 3 bulan setelah menghentikan pengobatan ethambutol. Semua pasien menjalani pemeriksaan neuro-oftalmologi, termasuk ketajaman visual, penglihatan warna, bidang visual dan funduscopy. Tomografi koherensi optik (Oktober) dilakukan pada kedua mata setiap pasien menggunakan lapisan serabut saraf protokol analisis retina. Interval antara penghentian pengobatan ethambutol dan kunjungan awal berkisar antara 1 minggu sampai 3 bulan. Semua pasien memiliki defisit visual karakteristik neuropati optik etambutol-induced pada kunjungan awal mereka, dan pemeriksaan tindak lanjut dilakukan dalam waktu 12 bulan. Dibandingkan dengan retina serat saraf ketebalan lapisan awal (RNFLT), terjadi penurunan signifikan secara statistik pada RNFLT rata-rata temporal, superior dan hidung kuadran (p = 0,009, 0,019 dan 0,025 masing-masing), dengan penurunan terbesar dalam temporal kuadran (rata-rata penurunan 26,5 mum). Penurunan RNFLT yang diamati di semua kuadran pada pasien dengan neuropati etambutol-induced optik yang baru dihentikan obat. Penurunan ini paling menonjol di kuadran temporal dari disk optik. [Chai S, Foroozan R, Br J Ophthalmol 91 (7): 895-7 (2007)] ** peer review ** PubMed Abstrak

/ STUDI SAMBUNGAN MANUSIA / Dari Januari 1984-Desember 1987, 1783 pasien menerima terapi kombinasi isoniazid, rifampisin, dan etambutol untuk pengendalian tuberkulosis. Empat puluh dua dikembangkan hepatitis gejala selama periode pengobatan. Lima belas adalah pembawa virus hepatitis B, dan sisanya 27 orang noncarriers. Puncak serum transaminase dan kadar bilirubin lebih tinggi pada operator. Tujuh operator meninggal fulminan atau subakut kegagalan hati, dan hanya 1 noncarrier meninggal. Sebelas operator memiliki terdeteksi virus asam deoksiribonukleat serum hepatitis B selama tahap akut hepatitis. [Wu JC dkk, Gastroenterologi 98 (2): 502-4 (1990)] ** peer review ** PubMed Abstrak

/ TANDA DAN GEJALA / Efek samping yang paling penting dari etambutol adalah neuritis optik dengan penurunan ketajaman visual, penyempitan bidang visual, scotomas pusat dan perifer, dan hilangnya diskriminasi warna merah-hijau. Tingkat toksisitas okular tampaknya berhubungan dengan dosis dan durasi terapi etambutol. Namun, keracunan seperti itu juga telah dilaporkan jarang setelah hanya beberapa hari terapi dengan obat, dan dapat mewakili reaksi istimewa. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

/ KASUS LAPORAN / / Penyidik / melaporkan kasus seorang laki-laki tua yang reaksi dengan erupsi kulit paru terjadi pada tahap awal kemoterapi terdiri dari isoniazid, rifampisin, dan etambutol (EB). Sebuah tes stimulasi limfosit perifer (LST) menunjukkan reaksi positif hanya untuk EB. Darah analisis serum pasien ketika reaksi ini terjadi mengungkapkan peningkatan titer antibodi antinuklear. Computed tomography (CT) scan film dada ketika reaksi paru terjadi menunjukkan konsolidasi subpleural multifokal. Ada hanya satu melaporkan kasus EB-induced reaksi paru dan tentu saja klinis sangat mirip dengan / satu dijelaskan di sini /. [Hiraoka K et al, J UOEH 20 (2): 145-51 (1998)] ** peer review ** PubMed Abstrak

/ KASUS LAPORAN / Seorang wanita berusia 67 tahun yang disajikan dengan tuberkulosis miliaria. Dia diperlakukan dengan streptomisin, isoniazid, rifampisin, etambutol dan pirazinamid. Namun, dia mengembangkan rifampisin-induced trombositopenia setelah 6 minggu pengobatan, dan ruam kulit, eosinofilia darah dan infiltrat paru setelah 8 minggu terapi. Yang terakhir ditemukan etambutol terkait. Bukti tambahan, termasuk darah dan dahak eosinofilia dan kecepatan dari respon terhadap kortikosteroid, menyarankan bahwa infiltrat paru juga mungkin eosinofilik di alam. [Wong P et al, Eur Pernafasan J 8 (5): 866-8 (1995)] ** peer review ** PubMed Abstrak

/ KASUS LAPORAN / Seorang pria 55-tahun datang dengan kecurigaan TB paru. Dia diperlakukan dengan isoniazid, etambutol, rifampisin dan pirazinamid. Namun, ia mengalami demam tinggi, ruam kulit dan infiltrat paru setelah 10 hari pengobatan. Kondisi di atas mereda segera setelah menghentikan terapi etambutol dan muncul kembali setelah rechallenge, menandai etambutol sebagai pelaku. [Chien H et al, Zhonghua Yi Xue Za Zhi (Taipei) 61 (6): 371-4 (1998)] ** peer review ** PubMed Abstrak

/ KASUS LAPORAN / Seorang wanita mengembangkan neuropati perifer dan neuritis optik saat menerima etambutol dalam penafsiran tuberkulosis paru yang resistan terhadap obat. Ada peningkatan cepat dalam neuropati perifer dan gejala okular setelah penghentian obat. [Nair V dkk, Dada 77 (1): 98-100 (1980)] ** peer review ** PubMed Abstrak

/ KASUS LAPORAN / Seorang gadis 10 tahun dengan TB serviks diobati dengan Isoniazid, Rimfampicin dan Etambutol. Setelah 2 minggu pengobatan reaksi hepatotoksik dikembangkan. Penarikan terapi menghasilkan perbaikan klinis yang lengkap dan normalisasi semua pengukuran laboratorium. Pengobatan dimulai kembali dengan Rifampisin, Etambutol dan Pyrazinamid. Tingkat enzim hati dipantau mingguan. Tujuh minggu setelah resimen ini tiga jenis obat dimulai, semua terapi dihentikan karena tingkat enzim hati yang tinggi. Namun, pasien meninggal 2 minggu kemudian hepatitis fulminan progresif. [Van Aalderen WM dkk, Eur J Pediatr 146 (3): 290-1 (1987)] ** peer review ** PubMed Abstrak

/ KASUS LAPORAN / / Penulis / melaporkan kasus seorang pria 51 tahun yang diduga tuberkulosis (TB) pleuritis. Sebuah percobaan anti-TB dengan INH, rifampisin dan etambutol (EMB) diberikan pada awalnya. Pening, disorientasi, dan halusinasi auditori dan visual yang dikembangkan setelah tujuh hari terapi. Pemeriksaan laboratorium, termasuk tes rutin biokimia, titer serum antibodi antinuklear, analisis cairan serebrospinal dan computerized tomography kepala tidak menunjukkan temuan abnormal. Setelah penghentian agen anti-TB, gejala kejiwaan mereda. Ketika pasien ditantang dengan EMB, gejala kejiwaan yang sama terulang, tapi diselesaikan lagi setelah penghentian EMB. [Hsu CW et al, Zhonghua Yi Xue Za Zhi (Taipei) 62 (10): 724-7 (1999)] ** peer review ** PubMed Abstrak

/ KASUS LAPORAN / Dua pasien dengan kehilangan penglihatan bilateral karena toksisitas etambutol menjalani mfERG pengujian yang diungkapkan baik menyebar dan tengah kerugian bidang kompatibel dengan disfungsi retina sebagai mekanisme berkontribusi terhadap hilangnya bidang visual. Toksisitas etambutol tidak hanya mempengaruhi saraf optik tapi elemen retina mungkin lain berdasarkan temuan mfERG abnormal. [Kardon R et al, Semin Ophthalmol 21 (4): 215-22 (2006)] ** peer review ** PubMed Abstrak

Peringatan Obat:

Studi yang tepat tentang hubungan usia terhadap efek etambutol belum dilakukan pada anak-anak sampai usia 13 tahun. Etambutol umumnya tidak dianjurkan pada anak-anak yang ketajaman visual tidak dapat dipantau (lebih muda dari usia 6 tahun). Namun, etambutol harus dipertimbangkan untuk semua anak dengan organisme yang resisten terhadap obat lain, dan siapa kerentanan terhadap etambutol telah dibuktikan atau mungkin. [Thomson / Micromedex. Informasi Obat untuk Perawatan Kesehatan Profesional. Volume 1, Greenwood Village, CO 2007., P. 1335] ** peer review **

Efek samping yang paling penting dari etambutol adalah neuritis optik dengan penurunan ketajaman visual, penyempitan bidang visual, scotomas pusat dan perifer, dan hilangnya diskriminasi warna merah-hijau. Tingkat toksisitas okular tampaknya berhubungan dengan dosis dan durasi terapi etambutol. Namun, keracunan seperti itu juga telah dilaporkan jarang setelah hanya beberapa hari terapi dengan obat, dan dapat mewakili reaksi istimewa. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

Dampak merugikan lainnya dari etambutol termasuk dermatitis, pruritus, sakit kepala, malaise, pusing, demam, kebingungan mental, disorientasi, halusinasi mungkin, nyeri sendi, dan reaksi anafilaktoid jarang. GI marah, sakit perut, mual, muntah, dan anoreksia juga terjadi kadang-kadang dengan ethambutol. Neuritis perifer, dengan mati rasa dan kesemutan pada ekstremitas, telah dilaporkan jarang. Konsentrasi asam urat dalam darah meningkat dan curah hujan gout akut terjadi sesekali pada pasien yang menerima etambutol dan mungkin hasil dari penurunan klirens ginjal urat. Penurunan sementara fungsi hati, seperti yang ditunjukkan oleh hasil tes fungsi hati yang abnormal, juga telah terjadi. Ikterus kolestatik, yang tampaknya disebabkan oleh ethambutol, telah dilaporkan dalam setidaknya satu pasien yang menerima obat baik sendiri maupun dalam hubungannya dengan streptomisin. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

Pengujian visual harus dilakukan sebelum memulai terapi etambutol dan kemudian secara periodik selama terapi dengan obat. Pengujian harus dilakukan setiap bulan pada pasien yang menerima lebih dari 15 mg / kg sehari. Pemeriksaan harus mencakup oftalmoskopi, jari perimetry, dan pengujian diskriminasi warna. Pasien mengembangkan efek samping okular selama terapi etambutol dapat menunjukkan gejala visual yang subjektif baik sebelum atau bersamaan dengan penurunan ketajaman visual. Semua pasien yang menerima obat harus dipertanyakan secara berkala tentang penglihatan kabur dan gejala visual yang subjektif lain dan harus diinstruksikan untuk melaporkan kepada dokter mereka setiap perubahan tersebut sesegera mereka perhatikan. Jika perubahan substansial dalam ketajaman visual terjadi, etambutol harus dihentikan segera. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

Pabrikan menyatakan bahwa etambutol tidak boleh digunakan pada anak-anak muda dari 13 tahun. The American Thoracic Society (ATS), US Centers for Disease Control dan Pencegahan (CDC), dan Infectious Diseases Society of America (IDSA) menyatakan bahwa etambutol harus digunakan dengan hati-hati pada anak-anak di antaranya mungkin sulit untuk memantau ketajaman visual (misalnya , mereka lebih muda dari 5 tahun). Para ahli menyatakan bahwa etambutol biasanya dianjurkan untuk digunakan pada anak-anak tersebut hanya ketika strain Mycobacterium tuberculosis yang terlibat diketahui atau diduga resisten terhadap isoniazid atau rifampin atau saat anak mengalami tipe dewasa (infiltrasi lobus atas, pembentukan rongga) TBC. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

Ginjal, hati, dan tes hematopoietik harus dilakukan secara periodik selama terapi etambutol jangka panjang. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

Etambutol merupakan kontraindikasi pada pasien dengan neuritis optik kecuali penilaian klinis menganggap perlu bahwa obat dapat digunakan. Etambutol juga kontraindikasi pada pasien yang diketahui hipersensitif terhadap obat tersebut. [McEvoy, G.K. (Ed.). American Hospital Layanan formularium. AHFS Informasi Obat. American Society of Health-System Apoteker, Bethesda, MD. 2007., P. 551] ** peer review **

Konsentrasi asam urat serum mungkin diperlukan selama pengobatan karena konsentrasi asam urat serum sering terjadi, mungkin pencetus gout akut. Menggigil, nyeri dan pembengkakan sendi jari kaki-terutama besar, pergelangan kaki atau lutut, tegang, kulit panas di atas sendi yang terkena menunjukkan kebutuhan untuk perhatian medis. [Thomson / Micromedex. Informasi Obat untuk Perawatan Kesehatan Profesional. Volume 1, Greenwood Village, CO 2007., P. 1336] ** peer review **

Obat ibu biasanya Kompatibel dengan Menyusui: Etambutol: Masuk dilaporkan atau gejala di Bayi atau Efek pada Laktasi: Tidak ada. / Dari Tabel 6 / [Laporan dari American Academy of Pediatrics Komite Narkoba di Pediatrics 93 (1): 141 (1994)] ** peer review **

Tuberkulosis tidak lebih sering, atau lebih serius pada ibu hamil dibandingkan wanita yang tidak hamil. Risiko bagi anak adalah tiga: dua kali lipat dalam tingkat kematian karena penyakit pada ibu jika dia tidak diobati, risiko toksisitas terkait dengan obat anti-TB dan risiko infeksi TB saat lahir. Isoniazid dan etambutol memiliki toksisitas yang lemah. Kedua antibiotik dapat diresepkan selama kehamilan (setelah mengkonfirmasi adanya Kekurangan vitamin B6 pada ibu). Pengobatan tuberkulosis pada kehamilan akan rifampisin + isoniazid + etambutol (etambutol yang sedang berhenti setelah dua bulan dan isoniazid dan rifampisin setelah 9 mo pengobatan). Pada saat persalinan, jika TB ibu dikonfirmasi bakteriologis pada saat mikroskop, kemoprofilaksis akan dimulai pada bayi yang baru lahir dengan isoniazid, sampai ibu bakteriologis negatif pada pemeriksaan mikroskopis, bayi yang baru lahir kemudian harus divaksinasi dengan BCG. Jika pengobatan ibu dengan benar ditentukan dan menyusui diikuti adalah mungkin dan tidak ada isolasi baik ibu atau anak diperlukan. Amt dari antibiotik yang lewat di susu ibu minimal dan makanan tertentu seperti tidak boleh ditiadakan jika pengobatan diperlukan. [Dautzenberg B, Grosset J, Rev Mal Pernafasan 5 (3): 279-83 (1988)] ** peer review ** PubMed Abstrak