Source: European Medicines Agency (EU) Revision Year: 2017 Publisher: SUPPLIER: Macleods Pharmaceuticals Limited, 304, Atlanta Arcade, Marol Church road, Andheri (East), Mumbai – 400 059, India, Tel: +91-22-66762800, Fax: +91-22-28216599
Hypersensitivity to ethionamide/protionamide or to any of the excipients.
Severe hepatic impairment.
The use of ethionamide alone in the treatment of tuberculosis results in rapid development of resistance. It is essential, therefore, to co-administer suitable other antituberculous drug or drugs, the choice being based on results of susceptibility testing. However, therapy may be initiated prior to receiving the results of susceptibility tests, as deemed appropriate by the health care provider.
Toxic hepatitis, obstructive jaundice, acute hepatic necrosis, as well as modest elevations of hepatic transaminase levels, bilirubin and alkaline phosphatase with or without jaundice, have been described during ethionamide treatment. Baseline liver function tests should be performed prior to therapy, and serum transaminases should be monitored every 2-4 weeks during therapy. If transaminase levels exceed five times the ULN, with or without symptoms, or three times the ULN with jaundice and/or hepatitis symptoms, Ethionamide 125 mg Dispersible Tablets and other potentially hepatotoxic co-administered drugs should be discontinued temporarily until the laboratory abnormalities have resolved. These medications may then be reintroduced sequentially to determine which drug (or drugs) is (are) responsible for the hepatotoxicity. An increased risk of hepatotoxicity has been described in patients with diabetes mellitus.
Psychotic disturbances, encephalopathy, peripheral and optic neuritis, as well as a pellagra-like syndrome have been reported with ethionamide. In some cases, these symptoms have improved with nicotinamide and pyridoxine substitution. Therefore, concurrent administration of pyridoxine is recommended to prevent neurotoxic effects of ethionamide.
Since ethionamide treatment has been associated with hypoglycaemia, blood glucose should be determined prior to and periodically throughout therapy with Ethionamide 125 mg Dispersible Tablets. Blood glucose control in diabetes mellitus may be more difficult during ethionamide treatment, including an increased risk of hypoglycaemia.
Periodic monitoring of thyroid function is recommended as hypothyroidism, with or without goitre, has been reported with ethionamide therapy.
Ethionamide may cause severe allergic hypersensitivity reactions with rash and fever. If this occurs, Ethionamide 125 mg Dispersible Tablets must be discontinued.
Since ethionamide may cause visual disturbances, ophthalmoscopy is recommended before and periodically during therapy with Ethionamide 125 mg Dispersible Tablets
Co-administration of ethionamide and rifampicin has been associated with a high frequency of hepatitis with jaundice. In one study, hepatitis occurred in 4.5% of patients co-treated with rifampicin and ethionamide. The mortality in this subset of patients was 26%. Co-administration should be avoided unless the benefits are considered to outweigh the risks, and if so, the patient should be regularly monitored for liver function test abnormalities, as well as clinical signs and symptoms of liver dysfunction.
Co-administration of ethionamide and isoniazid increased the serum concentration of the latter in both rapid and slow acetylators. If co-administration is deemed necessary supplemental pyridoxine should be given; also monitor for adverse effects of isoniazid (peripheral neuritis, hepatotoxicity, encephalopathy).
A reversible pellagra-like encephalopathy has occurred when ethionamide and cycloserine were coadministered. This may have been caused by disturbances in pyridoxine metabolism.
Excessive use of ethanol during ethionamide therapy has been reported to precipitate a psychotic reaction and should thus be avoided.
Ethionamide has been demonstrated to have a teratogenic potential in rabbits and rats (see section 5.3). Some data indicate an excess of congenital malformations when ethionamide is given to pregnant women. Therefore ethionamide should be withheld from women who are pregnant, or are likely to become pregnant during therapy, unless the benefit is considered to outweigh the risk.
It is not known whether ethionamide is excreted into human milk. In case of breast-feeding during treatment with Ethionamide 125 mg Dispersible Tablets, the baby should be monitored for side effects of ethionamide (see section 4.8).
No data on the effect of ethionamide on fertility are available.
No studies on the effects on the ability to drive and use machines have been performed. Nevertheless, the clinical status of the patient and the adverse reaction profile of Ethionamide 125 mg Dispersible Tablets should be borne in mind when considering the patient’s ability to drive or operate machinery.
Adverse events considered to be at least possibly related to treatment with ethionamide are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000) or very rare (≤1/10,000). In addition, adverse events identified during post-approval use of ethionamide are listed (frequency category: ‘not known’). Since they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been included for their potential causal connection to ethionamide, taking also into account their seriousness and the number of reports.
Not known: thrombocytopenia.
Not known: pellagra-like syndrome, hypothyroidism, hypoglycaemia.
Not known: psychotic reactions.
Common: headache, dizziness, drowsiness, asthenia, paresthaesia
Not known: encephalopathy, peripheral neuritis, olfactory disturbance.
Not known: postural hypotension.
Very common: epigastric discomfort, abdominal pain, anorexia, nausea, vomiting, diarrhoea
Not known: metallic taste and sulphurous belching, increased salivation, taste disorders.
Very common: elevated serum transaminases
Common: hepatitis, jaundice.
Not known: rash, urticaria, acne, photosensitivity, stomatitis, alopecia, purpura.
Not known: gynaecomastia, menstrual disturbance, impotence.
Not known: visual disturbances (e.g. diplopia, blurred vision, optic neuritis).
Not known: ototoxicity.
Not known: hypersensitivity reaction (rash, fever)
Not applicable.
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