Isoniazid 100 Mg Tablets

ISONIAZID 100 mg PHARMA-Q is indicated alone for the prophylaxis of tuberculosis and in conjunction with other antituberculosis medicines for the treatment of tuberculosis.

Posology

Adults

Usual dose: 100 mg three times daily without meals. Recommended dose: 3 to 5 mg per kg body mass every 24 hours in two or more doses.

Children

10 to 20 mg per kg body mass daily. Prescribers should also consult the National Anti-tuberculosis Guidelines in regard to dosages of isoniazid.

Method of administration

Oral use. It may be preferable to take ISONIAZID 100 mg PHARMA-Q without meals. If aluminium containing antacids are taken, they must be taken at least one hour after ISONIAZID 100 mg PHARMA-Q (see section 4.5). ISONIAZID 100 mg PHARMA-Q may be taken with meals if gastrointestinal irritation occurs, but oral absorption may be reduced. Patients who are slow acetylators may be more prone to adverse effects and may require lower than usual doses. Tuberculosis therapy must be continued for 6 months to 2 years, depending on the treatment given.

• Hypersensitivity to isoniazid, ethionamide, pyrazinamide, niacin, or other chemically related medicines or to any of the excipients in ISONIAZID 100 mg PHARMA-Q (see section 6.1).
• Alcoholism.
• Hepatic function impairment.
• Severe renal failure.
• Seizure disorders.
• Pregnancy and lactation (see section 4.6).

All patients should have baseline liver function tests performed and repeated at regular intervals during treatment. If serum aspartate aminotransferase (AST) rises to more than three times normal, or there is any increase in bilirubin, treatment should be withdrawn.

ISONIAZID 100 mg PHARMA-Q should not be given to patients who have experienced severe adverse reactions including medicine-induced liver disease. Care should be taken in giving ISONIAZID 100 mg PHARMA-Q to patients suffering from convulsive disorders, diabetes mellitus, or impaired kidney function or to patients taking other potentially hepatotoxic medicines. ISONIAZID 100 mg PHARMA-Q may cause severe and sometimes fatal age-related hepatitis. If symptoms of hepatitis such as malaise, fatigue, anorexia, and nausea develop, ISONIAZID 100 mg PHARMA-Q 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. Periodic eye examination during treatment is recommended.

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 100 mg PHARMA-Q, but liver enzymes are raised only transiently. Concurrent use of other hepatotoxic medicines with ISONIAZID 100 mg PHARMA-Q may increase the potential for hepatotoxicity.

Isoniazid can inhibit the hepatic metabolism of a number of medicines, in some cases leading to increased toxicity. These include the antiepileptics carbamazepine, ethosuximide, primidone, and phenytoin, the benzodiazepines diazepam and triazolam, chlorzoxazone, and disulfiram. Concomitant benzodiazepine (diazepam, triazolam) and isoniazid therapy has been reported to result in an increased risk of benzodiazepine toxicity (sedation, respiratory depression). Adverse reactions have occurred when ISONIAZID 100 mg PHARMA-Q has been given with warfarin. 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). Phenytoin dosage adjustment may be necessary during and after ISONIAZID 100 mg PHARMA-Q therapy especially in slow acetylators of isoniazid.

Isoniazid may increase renal excretion of pyridoxine; requirements for pyridoxine may be increased in patients receiving isoniazid concurrently. Concurrent use of isoniazid may reduce the metabolism of theophylline, increasing theophylline plasma concentrations. Propranolol has been reported to cause significant reduction in the clearance of concurrently administered isoniazid. Concurrent administration of ISONIAZID 100 mg PHARMA-Q with paracetamol, alcohol and rifampicin may lead to a higher incidence of hepatotoxicity. Concurrent use of cycloserine or disulfiram with isoniazid results in increased incidence of central nervous system effects such as dizziness or drowsiness, dosage adjustment may be necessary, and patients should be monitored closely for signs of central nervous system toxicity especially if performing tasks requiring alertness. ISONIAZID 100 mg PHARMA-Q may reduce the therapeutic effects of levodopa. ISONIAZID 100 mg PHARMA-Q itself may be affected by other compounds, namely alcohol, aminosalicylic acid, antacids, corticosteroids, ketoconazole, propranolol, pyridoxine and sodium and sodium salicylate. Concomitant administration of ISONIAZID 100 mg PHARMA-Q 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.

Chronic use of ISONIAZID 100 mg PHARMA-Q may decrease the plasma clearance and/or prolong the duration of action of alfentanil, warfarin, benzodiazepines, carbamazepine, phenytoin and theophylline. Aluminium containing antacids may delay and decrease absorption and serum concentrations of isoniazid, therefore, ISONIAZID 100 mg PHARMA-Q should be given at least 1 hour before the antacid. ISONIAZID 100 mg PHARMA-Q may increase the formation of potentially nephrotoxic inorganic fluoride metabolites when used concurrently with enflurane. False positive reactions with copper sulphate urine glucose tests may occur.

Anti-retroviral medicines

Because the clearance of isoniazid was found doubled when zalcitabine was given in HIV-positive patients, concurrent use of ISONIAZID 100 mg PHARMA-Q and zalcitabine should be monitored to ensure isoniazid effectiveness. There may be an increased risk of distal sensory neuropathy when ISONIAZID 100 mg PHARMA-Q is used in patients taking stavudine (d4T). ISONIAZID 100 mg PHARMA-Q should be used with caution with stavudine and zalcitabine as stavudine, zalcitabine and isoniazid have been associated with causing peripheral neuropathy.

Alcohol

The metabolism of isoniazid, ISONIAZID 100 mg PHARMA-Q may be increased in chronic alcoholics. This may lead to reduced isoniazid effectiveness. These patients may also be at increased risk of developing ISONIAZID 100 mg PHARMA-Q induced peripheral neuropathies and hepatic damage.

Concurrent use of ISONIAZID 100 mg PHARMA-Q with other neurotoxic medicines may produce additive neurotoxicity. ISONIAZID 100 mg PHARMA-Q may cause niacin deficiency by inhibiting niacin incorporation into nicotinamide adenine dinucleotide.

Food interactions

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).

Pregnancy

Isoniazid, as in ISONIAZID 100 mg PHARMA-Q, crosses the placenta. ISONIAZID 100 mg PHARMA-Q should be avoided during pregnancy (see section 4.3).

Breastfeeding

Isoniazid passes into breast milk. Women on treatment with ISONIAZID 100 mg PHARMA-Q should not breastfeed their infants.

ISONIAZID 100 mg PHARMA-Q may cause dizziness, impaired concentration, and/or drowsiness. Patients should be instructed that if they experience these symptoms, they should avoid potentially hazardous tasks such as driving or operate machinery.

a. Summary of the safety profile

Undesirable effects are listed by MedDRA System Organ Classes and frequency: Frequent, Less frequent, Frequency unknown (cannot be estimated from the available data).

b. Tabulated summary of adverse reactions

MedDRA system organ class Frequency Adverse reactions

Blood and lymphatic system disorders Less frequent Haematological effects (various anaemias, agranulocytosis, thrombocytopenia and eosinophilia).

Immune system disorders Less frequent Hypersensitivity reactions (fever, skin rashes, joint pain) Frequency unknown Lymphadenopathy

Metabolism and nutrition disorders Less frequent Hyperglycaemia, metabolic acidosis, hypoglycaemia Frequency unknown Pellagra (nicotinic acid deficiency). Nicotinic acid deficiency may be related to an isoniazid-induced pyridoxine deficiency which effects the conversion of tryptophan to nicotinic acid.

Psychiatric disorders Less frequent Neurotoxicity (psychotic reactions) Frequency unknown Psychotic disorder; euphoria. 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 medicine.

Nervous system disorders Frequent Peripheral neuritis Less frequent Convulsions, hyperreflexia Frequency unknown Peripheral neuropathy, seizure, optic neuritis

Eye disorders Less frequent Optic neuritis

Ear and labyrinth disorders Less frequent Vertigo Frequency unknown Deafness, tinnitus. These have been reported in patients with end stage renal impairment. Vertigo may be troublesome with doses of 10 mg per kg body weight.

Vascular disorders Frequency unknown Vasculitis

Respiratory, thoracic and mediastinal disorders Frequency unknown Interstitial lung disease

Gastrointestinal disorders Frequent Nasea, vomiting, constipation, dry mouth, gastrointestinal irritation Frequency unknown Pancreatitis and other gastrointestinal effects

Hepato-biliary disorders Frequent Hepatitis, hepatitis prodromal symptoms (loss of appetite, nausea or vomiting, unusual tiredness or weakness), transient increases in liver enzymes Frequency unknown 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.

Skin and subcutaneous tissue disorders Less frequent Skin reactions such as purpura, acneform syndrome, lupus erythematosus-like syndrome, exfoliative dermatitis, pellagra, alopecia, urticaria, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS). Frequency unknown Erythema multiforme, Stevens-Johnson syndrome

Musculoskeletal and connective tissue disorders Frequency unknown Systemic lupus erythematosus, Lupus-like syndrome, rheumatoid syndrome

Renal and urinary disorders Less frequent Urinary retention Frequency unknown Dysuria

Reproductive system and breast disorders Less frequent Gynaecomastia

General disorders and administration site conditions Frequency unknown Pyrexia

Investigations Frequency unknown Increased hepatic enzymes

c. Description of selected adverse reactions

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

Symptoms

Patients may be asymptomatic for 30 minutes to 2 hours after an acute overdose. Early symptoms include, nausea, vomiting, dizziness, slurred speech, lethargy, disorientation and hyper-reflexia. Seizure usually occurs within 1 to 3 hours after ingestion and are often repetitive and refractory to usual anticonvulsants. Metabolic acidosis occurs within a few hours. Hyperglycaemia, glycosuria and ketonuria have been reported.

Treatment

Treatment for overdosage is symptomatic and supportive therapy. Including the control of convulsions by diazepam given intravenously, together with large doses of pyridoxine. Metabolic acidosis is corrected with sodium bicarbonate.