Isoniazid

Isoniazid Chemical Structure : Isoniazid in Kenya:

ISONIAZID MODE OF ACTION:

Isoniazid inhibits the synthesis of mycolic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.

Drug Label Information | Brands:

Brands of Isoniazid in Kenya

Bitub®, Yuria Pharma Limited
Isoniazid, Macleods Pharmaceuticals Limited
Isoniazid, Cosmos Limited
Isozide® , Nabiqasim Industries (Pvt). Ltd.

ISONIAZID INDICATIONS:

Isoniazid is indicated in the treatment of all forms of pulmonary and extra-pulmonary tuberculosis.

However, active tuberculosis must be treated with multiple concomitant antituberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculosis with isoniazid, or any other medication, is inadequate therapy.

DOSAGE AND ADMINISTRATION:

Adults

The dose of isoniazid for the treatment of tuberculosis is commonly 4 to 5mg per kilogram body-weight daily given by mouth in single or divided doses up to a maximum of 300mg daily. Up to 10mg per kilogram body-weight daily may be given particularly during the first 1 to 2 weeks of treatment of tuberculous meningitis. A dose of 15mg per kilogram has been given two or three times weekly in intermittent treatment regimens.

Elderly

No dosage reduction is necessary in the elderly, but caution should be exercised due to the possible decrease in renal and hepatic function.

Paediatric population

The usual daily dose for children aged three months and above is from 10 up to 15mg per kilogram body-weight daily in single or divided doses.

Isoniazid should not be used in children aged 0 to 3 months because of the lack of specific data.

CONTRAINDICATIONS:

Patients who are known to be hypersensitive to isoniazid or drug-induced liver disease

DRUG INTERACTIONS:

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).

Pyridoxine is the naturally occurring form of vitamin B6. Following absorption from the gastrointestinal tract, it is converted in the liver to a coenzyme, pyridoxal phosphate, that is involved in many metabolic processes. Isoniazid interferes competitively with pyridoxine metabolism by inhibiting the formation of the active form of the vitamin, and hence often results in peripheral neuropathy.

There may be a potential interaction between isoniazid and foods containing histamine or tyramine.

ADVERSE DRUG REACTIONS:

Blood and lymphatic system disorders

Frequency not known: Agranulocytosis, Aplastic anaemia, Haemolytic anaemia

Ear and labyrinth disorders

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

Gastrointestinal disorders

Frequency not known: Constipation, Dry mouth Nausea, Pancreatitis acute, Vomiting and other gastrointestinal effects

General disorders and administration site conditions

Frequency not known: Pyrexia

Hepatobiliary disorders

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.

Investigations

Frequency not known: Hepatic enzyme increased

Metabolism and nutrition disorders

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.

Musculoskeletal and connective tissue disorders

Frequency not known: Systemic lupus erythematosus, lupus-like syndrome

Nervous system disorders

Frequency not known: Neuropathy peripheral, Optic neuritis, Seizure

Hyperreflexia may be troublesome with doses of 10mg per kg body weight

Psychiatric disorders

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

Renal and urinary disorders

Frequency not known: Dysuria

Reproductive system and breast disorders

Frequency not known: Gynaecomastia

Respiratory, thoracic and mediastinal disorders

Frequency not known: Interstitial lung disease

Skin and subcutaneous tissue disorders

Frequency rare: Toxic epidermal necrolysis, eosinophilia systemic symptoms, Frequency not known: Erythema multiforme, Stevens-Johnson syndrome,

Vascular disorders

Frequency not known: Vasculitis

Miscellaneous

Withdrawal symptoms, which may occur on the cessation of the treatment, include headache, insomnia, excessive dreaming, irritability and nervousness.

ISONIAZID OVERDOSE (Toxicity)

The most commonly reported adverse events associated with isoniazid overdose are nausea, vomiting and central nervous system toxicity such as vertigo, seizures and coma.

Treatment of overdosage consists of gastric lavage following intubation and the control of convulsions by anti-convulsants given intravenously as well as the intravenous injection of large doses of pyridoxine. Any acidosis is corrected with sodium bicarbonate. Forced diuresis may be tried and haemodialysis or peritoneal dialysis has been used.