Date of approval.
Date of revision.
Ethambutol Hydrochloride Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Ethambutol Hydrochloride Tablets
English Name: Ethambutol Hydrochloride Tablets
Hanyu Pinyin: YanSuan Yi’AnDingChun Pian
Ingredients
The main ingredient of this product: Ethambutol Hydrochloride
Chemical name: {2R,2[S-(R*,R*)]-R}-(+)2, 2′-(1,2-ethylenediimino)-bis-1-butanol dihydrochloride
Structural formula.
Molecular formula: C10H24N2O2-2HCl
Molecular weight: 227.23
Properties
This product is a film-coated tablet, which appears white or off-white after removing the coating.
Indications
It is used in combination with other anti-tuberculosis drugs for the treatment of pulmonary tuberculosis caused by Mycobacterium tuberculosis.
It can also be used for the treatment of tuberculous meningitis and atypical mycobacterial infection.
Specification】0.25g
Dosage]
1. Common dosage for adults
In combination with other anti-tuberculosis drugs, for primary treatment of tuberculosis, 15mg/kg by body weight, once daily in a single dose; or 25-30mg/kg per oral dose, up to 2.5g (10 tablets), 3 times a week; or 50mg/kg, up to 2.5g (10 tablets), twice a week. For tuberculosis re-treatment, 25mg/kg by body weight once daily in a dose for 60 days, followed by 15mg/kg by body weight once daily in a dose. For atypical mycobacterial infection, 15-25mg/kg once daily in a single dose.
2. The dosage for children under 13 years of age should not be used; the dosage for children over 13 years of age is the same as that for adults.
Adverse reactions]
1. Ethambutol hydrochloride may cause vision loss due to optic neuritis, including irreversible blindness. Optic neuropathy caused by ethambutol includes optic neuritis, retrobulbar optic neuritis, which manifests as one or more of the following symptoms: vision loss, dark spots, color blindness, visual defects. These symptoms have also been reported in patients without a diagnosis of optic neuritis or retrobulbar optic neuritis.
Patients need to report any change in visual acuity to their physician as soon as it occurs.
Changes in visual acuity may be unilateral or bilateral, so it is important to examine each eye individually as well as both eyes simultaneously. Vision examinations should be performed prior to initiation of treatment with ethambutol hydrochloride and periodically during the administration of the drug. If the patient’s daily dose exceeds 15 mg/kg, monthly visual acuity examinations should be performed. If, after careful evaluation, the magnitude of the visual acuity change is confirmed and no other cause is found, ethambutol hydrochloride should be discontinued and the patient should be evaluated more frequently. Persistent loss of vision during treatment must be considered to be related to ethambutol.
If corrective eyeglasses were worn prior to treatment, they must be worn at the time of the vision examination. Refractive errors may occur during the 1 to 2 years of treatment, so they must be corrected to obtain accurate test results. Refractive error can be eliminated by pinhole testing of vision. Patients who develop visual abnormalities during treatment with ethambutol hydrochloride may develop subjective visual symptoms before or concurrently with the diagnosis of vision loss, so all patients treated with ethambutol hydrochloride should be questioned periodically about blurred vision and other subjective ocular symptoms.
Recovery of vision generally occurs several weeks to months after discontinuation of the drug. Some patients have taken ethambutol hydrochloride again after recovery and have not experienced further vision loss.
2. Other adverse reactions reported include: hypersensitivity reactions, allergic/allergic-like reactions, dermatitis, erythema multiforme, pruritus, arthralgia; anorexia, nausea, vomiting, gastrointestinal distress, abdominal pain; fever, general malaise, headache, dizziness; confusion, disorientation, possible hallucinations; thrombocytopenia, leukopenia, neutropenia. Numbness and tingling in the extremities caused by peripheral neuritis has been reported. Elevated serum uric acid levels and acute gout have also been reported. Pulmonary infiltrates with or without eosinophilia during ethambutol hydrochloride treatment have also been reported. Hepatotoxicity, including death, has been reported. As ethambutol hydrochloride is used in combination with one or more antituberculosis drugs, it is possible that these changes are related to the combination. Hypersensitivity syndromes include skin reactions (e.g., rash or exfoliative dermatitis), eosinophilia, and one or more of the following: hepatitis, pneumonia, nephritis, myocarditis, and pericarditis. Fever and lymph node enlargement may also occur.
[Contraindications].
1. patients with a history of hypersensitivity to the ingredients contained in this preparation.
2. The following patients are contraindicated in principle and caution is required when using this product for special necessity.
(1) Patients with optic neuritis: may aggravate the damage to vision.
(2) Patients with diabetes mellitus, alcoholism: risk of worsening symptoms in cases that have already caused optic nerve disorders.
(3) Infants and children: Early stages of visual impairment are difficult to detect.
【Caution】.
1. This product may cause vision loss due to optic neuritis. This effect may be related to the dose administered and the time of administration. This reaction is usually reversible when administration is stopped. However, irreversible blindness has been reported. Because ethambutol may have adverse effects on vision, a physical examination should include fundoscopy, finger visual field examination, and color discrimination testing. Assessment of visual changes is more difficult in patients with visual defects such as cataracts, recurrent inflammation of the eye, optic neuritis, and diabetic retinopathy, and care should be taken to ensure that visual changes are not caused by the underlying disease. Because assessment of visual changes is more difficult in such patients, care should be taken to weigh the pros and cons of the expected benefit against possible deterioration of vision (see [Adverse Reactions]).
2. Hepatotoxicity, including death, has been reported (see [Adverse Reactions]). Baseline examination and periodic evaluation of liver function should be performed.
3. Ethambutol hydrochloride is not recommended for use in pediatric patients under 13 years of age because the safety of its use has not been established.
4. The following conditions should be used with caution: gout, hyperalgesia.
5. Given that there is no practical method for determining blood levels, doses should be calculated based on patient weight. In patients with hepatic or renal decompensation, the blood concentration of this product may be increased and the half-life prolonged. The dose should be reduced in patients with reduced renal function.
6. Baseline examination and periodic evaluation of organ system functions including kidney, liver and hematopoietic system should be performed when taking this product.
7. The use of this product may increase the measured blood uric acid concentration and cause gout attacks. Therefore, it should be measured regularly during the course of treatment.
8. If gastrointestinal irritation occurs, ethambutol may be taken with food. The effective blood concentration may not be achieved by splitting the daily dose, therefore, it is recommended to take the daily dose in one dose.
9. Ethambutol alone can rapidly develop bacterial resistance, so it must be used in combination with other anti-tuberculosis drugs. This product should be used in combination with at least one other drug when used in patients who have received anti-tuberculosis drugs.
Pregnant women and nursing mothers
Pregnancy
Teratogenic effects: Pregnancy category C.
There are no adequate and well-controlled studies in pregnant women. Ocular abnormalities have been reported in infants born to women treated with antituberculosis drugs, including ethambutol. Ethambutol hydrochloride should be used in pregnant women only after a risk-benefit assessment of the fetus.
High doses of ethambutol hydrochloride have been shown to have teratogenic effects in pregnant mice and rabbits. When pregnant mice or rabbits received high doses of ethambutol hydrochloride administration, fetal mortality was slightly but not significantly increased (P>0.05). Female rats administered ethambutol hydrochloride showed a slight but non-significant decrease in fertility and litter size (P>0.05). A lower incidence of cleft palate, dewlap malformation, and spinal malformation was observed in pups born to pregnant mice receiving high doses of ethambutol hydrochloride administration. When pregnant rats received high doses of ethambutol hydrochloride administration, minor cervical spine abnormalities were observed in the pups born. In pregnant rabbits administered high doses of ethambutol hydrochloride, two one-eyed pups were observed, one with shortened right forearm with bilateral carpal contracture and the other with cleft lip and palate.
Lactating women
Ethambutol hydrochloride can be distributed to breast milk. Consider using ethambutol hydrochloride only if the current expected benefit to the nursing woman outweighs the potential risk to the infant.
Pediatric Dosage]
Ethambutol hydrochloride is not recommended for use in pediatric patients under 13 years of age because the safety of its use has not been established.
Geriatric Use]
Information on the use of ethambutol hydrochloride in the elderly is limited.
A study of multiple anti-tuberculosis drug regimens was conducted in 101 patients 65 years of age and older, 94 of whom were given ethambutol. No differences in safety or tolerability were observed in these patients compared with those reported in adults in general. Other reported clinical trials have not found differences in response between older and younger patients, but a higher sensitivity in some older adults cannot be ruled out.
Generally, elderly patients are more physically impaired and should reduce the dose as appropriate when first starting the drug. The elderly are often associated with physiologically reduced renal function, so the dosage should be adjusted according to renal function. Elderly patients are prone to visual impairment and should undergo regular vision examinations and pay close attention to the patient’s status while taking the drug.
Drug Interactions
1. Combined with ethylthioisonicotinamide may increase adverse reactions.
2. Combined with aluminum hydroxide can reduce the absorption of this product.
3. Combined with neurotoxic drugs may increase the neurotoxicity of this product, such as optic neuritis or peripheral neuritis. 4.
4. Combination with rifampicin may aggravate the adverse effects of visual impairment.
5. Serious liver damage may occur when combined with other anti-tuberculosis drugs (e.g. isoniazid, rifampicin, etc.) and regular liver function tests are required.
[Drug overdose].
Not yet known.
Pharmacology and Toxicology
This product is a synthetic antibacterial anti-tuberculosis drug. The mechanism of action has not been fully elucidated. It can penetrate into mycobacteria and interfere with RNA synthesis, thus inhibiting the reproduction of bacteria. So far, no cross-resistance between this product and other anti-tuberculosis drugs has been found.
Pharmacokinetics
1. Blood concentration
The maximum blood concentration (Cmax) of ethambutol hydrochloride 0.5g (4 tablets containing 125mg of ethambutol each) was 1.7μg/mL (in plasma) and the time to peak (Tmax) was 2.8 hours after oral administration on an empty stomach in healthy adult males.
In vitro studies have shown that ethambutol hydrochloride hardly binds to plasma proteins.
In patients with pulmonary tuberculosis, oral administration of 250 mg of ethambutol hydrochloride resulted in higher intra-erythrocyte concentrations than intra-serum concentrations.
2. Distribution
After oral administration of 0.5 g of ethambutol hydrochloride to patients with pulmonary tuberculosis, the drug concentration in lung tissue was not lower than the plasma drug concentration.
Higher concentrations of ethambutol hydrochloride were found in sputum after oral administration of 25 mg/kg of ethambutol hydrochloride in patients with pulmonary tuberculosis.
3. Metabolic excretion
The cumulative excretion rate of 14C-ethambutol hydrochloride was 54-61% in the urine after 24 h and 60-67% after 48 h. The excretion rate in the stool was 12-19% after 48 h in patients with pulmonary tuberculosis who received 25 mg/kg of 14C-ethambutol hydrochloride orally. Most of the urinary excretion is the prototype drug, and part of it is aldehyde or acid metabolite.
Storage
Storage】Store under shade and seal.
Package
Package】Packaged in aluminum-plastic blister, 100 tablets/box; 10 tablets/plate. Expiration date】18 months
Execution Standard
Approval Number】State Drug Administration H33021602
[Drug Marketing Licensee
Hangzhou Minsheng Pharmaceutical Co.
Manufacturer
Company Name: Hangzhou Minsheng Pharmaceutical Co.
Production Address: No. 36, Linping Avenue, Yuhang Economic and Technological Development Zone, Hangzhou
Postcode: 311100
Tel: 0571-88085858
Fax: 0571-88072129
Web address: www.mspharm.com