Source: European Medicines Agency (EU) Revision Year: 2016 Publisher: Supplier: Micro Labs Limited, #27, Race Course Road, Bangalore 560 001, Karnataka, India, Tel: +91-80-2237 0451 to 2237 0457, Fax: +91-80-2237 0463, Email: jainethesh@microlabs.in
The use of protionamide 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 physician.
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 reported during protionamide 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, Protionamide 250mg 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 thiamide antimycobacterials including Protionamide. In some cases, these symptoms have improved with nicotinamide and pyridoxine substitution. Therefore, concurrent administration of pyridoxine is strongly recommended to prevent neurotoxic effects of protionamide.
Since protionamide treatment has been associated with hypoglycaemia, blood glucose should be determined prior to and periodically throughout therapy with Protionamide 250mg Tablets. Blood glucose control in diabetes mellitus may be more difficult during protionamide treatment, including an increased risk of hypoglycaemia (see also section 4.5.).
Periodic monitoring of thyroid function is recommended as hypothyroidism, with or without goitre, has been reported during therapy with thiamide antimycobacterials such as protionamide.
Protionamide may cause severe allergic hypersensitivity reactions with rash and fever. If this occurs, Protionamide 250mg Tablets must be discontinued.
Since protionamide may cause visual disturbances, ophthalmoscopy is recommended before and periodically during therapy with Protionamide 250mg Tablets.
Protionamide 250mg Tablets contains FD&C yellow #6/sunset yellow FCF aluminium lake, an excipient which may cause allergic reactions.
Co-administration of rifampicin and thiamide antimycobacterials such protionamide has been associated with a high frequency of hepatitis with jaundice, possibly fatal. 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.
If protionamide and isoniazid are given concomitantly, then the concentration of protionamide in the blood is raised. Therefore, the protionamide dose should be reduced (=halved and not exceed 500 mg).
Protionamide slows down the decomposition of isoniazid.
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 use of protionamide should thus be avoided.
There are no or limited amount of data from the use of protionamide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).
Protionamide 250 mg Tablets should not be used during pregnancy, unless the clinical condition of the woman requires treatment with protionamide.
Protionamide has been identified in breastfed newborns/infants of treated women. The effect of protionamide on newborns/infants is unknown. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Protionamide 250 mg Tablets therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Supplementary pyridoxine (vitamin B6) is recommended both for the breastfeeding mother and the infant.
There are no data on the effects of protionamide/metabolites on human fertility. Effects on male and female fertility have not been evaluated in animal studies.
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 Protionamide 250mg 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 protionamide 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 protionamide 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 protionamide, taking also into account their seriousness and the number of reports.
Not known: thrombocytopenia.
Not known: pellagra-like syndrome, hypothyroidism, hypoglycaemia.
Not known: depression, confusion, difficulties concentrating, psychosis, suicide attempt.
Common: headache, dizziness, drowsiness, asthenia, paresthaesia
Not known: encephalopathy, peripheral neuritis, olfactory disturbance.
Not known: postural hypotension.
Very common: taste of metal or sulphur, dry mouth, increased salivation, anorexia, nausea
Uncommon: vomiting, heartburn, abdominal pain, feeling of fullness, diarrhoea, constipation, meteorism, swelling of the parotid
Very common: elevated serum transaminases
Common: hepatitis, jaundice.
Not known: Liver failure
Not known: pellagroid reactions, photodermatoses, rhagades, stomatitis, acne, cheilitis, glossitis, alopecia
Not known: gynaecomastia, menstrual disturbance, impotence.
Not known: visual disturbances (e.g. diplopia, blurred vision, optic neuritis).
Not known: ototoxicity.
Not known: arthralgia, arthritis
Not known: Urolithiasis
Not known: haemoptysis
Not known: allergic reactions
Not applicable.
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