Chemical formula: C₆H₇N₃O Molecular mass: 137.139 g/mol PubChem compound: 3767
Isoniazid interacts in the following cases:
Patients with severe renal failure (glomerular filtration rate of less than 10 ml/minute) and slow acetylator status might require a dose reduction of about 100mg to maintain trough plasma levels at less than 1 mcg/ml.
Antacids containing aluminum or magnesium reduce the absorption of isoniazid.
Concomitant benzodiazepine (diazepam) and isoniazid therapy has been reported to result in an increased risk of benzodiazepine toxicity (sedation, respiratory depression).
Isoniazid has been reported to cause substantial elevations of serum concentrations of carbamazepine and symptoms of carbamazepine toxicity at isoniazid doses of 200 mg 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).
The adverse CNS effects of cycloserine are increased by isoniazid.
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.
Isoniazid may reduce the therapeutic effects of levodopa.
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.
Prednisolone can lower plasma levels of isoniazid. Where a reduced response during concurrent use is noted, dosage adjustment of isoniazid may be necessary.
Isoniazid may induce abnormalities in liver function; this may be more likely when it is administered together with rifampicin.
There may be an increased risk of liver damage in patients receiving rifampicin and isoniazid but liver enzymes are raised only transiently.
There may be an increased risk of distal sensory neuropathy when isoniazid is used in patients taking stavudine (d4T).
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.
Isonaizid is removed by both haemodialysis and peritoneal dialysis therefore isoniazid should be administered immediately after dialysis.
Isoniazid should be used with caution in patients with a history of psychosis.
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 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 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. Supplementation with pyridoxine is recommended for breast-feeding women and for breastfed infants, to minimise adverse reactions.
Isoniazid is excreted in breast milk at concentrations equivalent to those found in maternal plasma, ie. 6-12 mcg/ml. This could result in an infant ingesting up to 2 mg/kg/day.
No specific statement, but unlikely to effect the ability to drive or use machinery. Patients should be warned of the possibility of convulsions, psychosis and optic neuritis.
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.
Side-effects have been reported mainly in association with high doses or in slow acetylators who develop higher blood levels of the drug.
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, Not known cannot be estimated from the available data.
Not known: Agranulocytosis, Anaemia including haemolytic, sideroblastic and aplastic, Eosinophilia, Thrombocytopenia
Not known: Lupoid syndrome
Not known: Pellagra, Hyperglycaemia
Not known: Psychosis
Not known: Peripheral neuropathy, Optic neuritis, Convulsions
Not known: Optic atrophy
Not known: Vasculitis
Not known: Pancreatitis
Uncommon: Hepatitis
Not known: Function liver abnormal, Jaundice
Rare: Toxic epidermal necrolysis, Eosinophilia systemic symptoms
Not known: Alopecia, Allergic skin reaction (including erythema multiforme), Purpura, Rash, Exfoliative dermatitis
Not known: Gynaeco-mastia
Not known: Fever
Isoniazid, especially if given with rifampicin, may induce abnormalities in liver function, particularly in patients with pre-existing liver disorders, in the elderly, the very young and the malnourished.
Peripheral neuropathy may be preventable with pyridoxine.
Severe and sometimes fatal hepatitis may occur with isoniazid therapy.
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