Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: RPH Pharmaceuticals AB, Lagervägen 7, 136 50 Haninge, Sweden
Patients who are known to be hypersensitive to isoniazid or drug-induced liver disease.
All patients should have baseline liver function tests performed and repeated at regular intervals during treatment. If serum AST rises to more than three times normal, or there is any increase in bilirubin, treatment should be withdrawn. Special precautions are required in patients with impaired liver function. Any deterioration in liver function in these patients is an indication for stopping treatment.
Isoniazid should not be given to patients who have experience severe adverse reactions including drug-induced liver disease. Care should be taken in giving isoniazid to patients suffering from convulsive disorders, diabetes mellitus, chronic alcoholism, or impaired liver or kidney function or to patients taking other potentially hepatoxic agents. If symptoms of hepatitis such as malaise, fatigue, anorexia, and nausea develop isoniazid should be discontinued immediately.
Isoniazid should be used with caution in patients with a history of psychosis.
Advanced age, female gender, slow acetylators, malnutrition, HIV infection, pre-existing liver disease, and extra-pulmonary tuberculosis were identified as risk factors for isoniazid-induced hepatotoxicity.
Patients who are at risk of neuropathy or pyridoxine deficiency, including those who are diabetic, alcoholic, malnourished, uraemic, pregnant, or infected with HIV, should be given pyridoxine.
When isoniazid is given to patients who inactivate it slowly or to patients receiving paraminosalicyclic acid concurrently, tissue concentrations may be enhanced, and adverse effects are more likely to appear. There may be an increased risk of liver damage in patients receiving rifampicin and isoniazid but liver enzymes are raised only transiently.
Isoniazid can inhibit the hepatic metabolism of a number of drugs, in some cases leading to increased toxicity. These include the antiepileptics carbamazepine, primidone, and phenytoin, the benzodiazepines diazepam and triazolam, chlorzoxazone, and disulfiram.
Isoniazid is an inhibitor of monoamine oxidase (MAO) and diamine oxidase (DAO), therefore can reduce tyramine and histamine metabolism, causing symptoms such as headache, sweating, palpitations, flushing, and hypotension. Patients should be advised against ingesting foods rich in tyramine and/or histamine during treatment with isoniazid, such as cured meat, some cheeses (e.g. matured cheeses), wine, beer and some fish (e.g. tuna, mackerel, salmon).
Isoniazid has been reported to cause substantial elevations of serum concentrations of carbamazepine and symptoms of carbamazepine toxicity at isoniazid doses of 200mg daily or more. The concurrent used is not recommended unless the effects can be closely monitored and suitable downward dosage adjustments made (a reduction between one-half or one-third was reported effective).
Concomitant benzodiazepine (diazepam) and isoniazid therapy has been reported to result in an increased risk of benzodiazepine toxicity (sedation, respiratory depression).
Isoniazid may reduce the therapeutic effects of levodopa.
Concomitant administration of isoniazid with itraconazole may result in significant decreases in itraconazole serum concentrations and therapeutic failure. Co administration is not recommended.
Isoniazid may decrease ketoconazole serum levels. Concurrent use should be well monitored and dosage increases made if necessary.
Because the clearance of isoniazid was found doubled when zalcitabine was given in HIV-positive patients, concurrent use of isoniazid and zalcitabine should be monitored to ensure isoniazid effectiveness.
There may be an increased risk of distal sensory neuropathy when isoniazid is used in patients taking stavudine (d4T).
There may be a potential interaction between isoniazid and foods containing histamine or tyramine.
Isoniazid crosses the placenta. Therefore, isoniazid should only be used in pregnant women or in women of child-bearing potential if the potential benefit justifies the potential risk to the foetus. It is considered that untreated tuberculosis represents a far greater hazard to a pregnant woman and her foetus than does treatment of the disease. Pyridoxine supplementation is recommended.
Isoniazid passes into breast milk. When administered to nursing mother, breast-fed infants should be monitored for possible signs of isoniazid toxicity. Administration of pyridoxine to the breast-feeding mother and infant may be considered.
No specific statement, but unlikely to effect the ability to drive or use machinery.
Undesirable effects are listed by MedDRA System Organ Classes.
Assessment of undesirable effects is based on the following frequency groupings: Very common: ≥1/10, Common: ≥1/100 to <1/10, Uncommon: ≥1/1,000 to <1/100, Rare: ≥1/10,000 to <1/1,000, Very rare: <1/10,000, Frequency not known: cannot be estimated from the available data.
The frequency of the reactions described below cannot be determined from the data available.
Frequency not known: Agranulocytosis, Aplastic anaemia, Haemolytic anaemia
Frequency not known: Deafness, Tinnitus, Vertigo
These have been reported in patients with end stage renal impairment.
Vertigo may be troublesome with doses of 10mg per kg body weight.
Frequency not known: Constipation, Dry mouth Nausea, Pancreatitis acute, Vomiting and other gastrointestinal effects
Frequency not known: Pyrexia
Frequency uncommon: Hepatitis
Frequency not known: Acute hepatic failure, Liver injury, Jaundice
The risk of these undesirable effects increases with age, especially over the age of 35; it may be serious and sometimes fatal with the development of necrosis.
Frequency not known: Hepatic enzyme increased
Frequency not known: Acidosis, Hypoglycaemia, Nicotinic acid deficiency
Nicotinic acid deficiency may be related to an isoniazid-induced pyridoxine deficiency which affects the conversion of tryptophan to nicotinic acid.
Frequency not known: Systemic lupus erythematosus, lupus-like syndrome
Frequency not known: Neuropathy peripheral, Optic neuritis, Seizure
Hyperreflexia may be troublesome with doses of 10mg per kg body weight.
Frequency not known: Elevated mood, Psychotic disorder
Although isoniazid usually has a mood elevating effect, mental disturbances, ranging from minor personality changes to major mental derangement have been reported; these are usually reversed on withdrawal of the drug.
Frequency not known: Dysuria
Frequency not known: Gynaecomastia
Frequency not known: Interstitial lung disease
Frequency rare: Toxic epidermal necrolysis, eosinophilia systemic symptoms
Frequency not known: Erythema multiforme, Stevens-Johnson syndrome,
Frequency not known: Vasculitis
Withdrawal symptoms, which may occur on the cessation of the treatment, include headache, insomnia, excessive dreaming, irritability and nervousness.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme on the MHRA website (www.mhra.gov.uk/yellowcard).
None.
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