Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about ISONIAZID tablets.

It does not contain all of the available information about ISONIAZID tablets. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking ISONIAZID tablets against the benefits they expect it will have.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What ISONIAZID is used for

The name of your medicine is ISONIAZID tablets which contains the active ingredient isoniazid.

Isoniazid belongs to a group of medicines called tuberculostatic agents. It acts by stopping the growth of the bacteria responsible for tuberculosis.

ISONIAZID is used to treat tuberculosis in combination with other antitubercular agents.

Ask your doctor if you have any questions about why ISONIAZID has been prescribed for you. Your doctor, however, may have prescribed it for another purpose.

ISONIAZID tablets are available only with a doctor’s prescription.

Before you take it

When you must not take it

Do not take ISONIAZID if:

• you are allergic to ISONIAZID tablets or any of their ingredients listed at the end of this leaflet.
  Some of the symptoms of an allergic reaction to ISONIAZID may include red, itchy skin rashes, difficulty breathing, hay fever, swelling of the face or throat or faintness.
• you have had severe reactions to ISONIAZID, for example fever, chills or arthritis.
• you have previously experienced liver problems after taking ISONIAZID tablets or any other medicines.
• you have acute liver problems from any cause.

Do not use ISONIAZID tablets after the expiry date (EXP.) printed on the pack. If you take it after the expiry date has passed, it may have no effect at all, or worse, there may be an entirely unexpected effect.

Do not purchase or use ISONIAZID tablets if the packaging is damaged or shows signs of tampering.

Elderly patients and patients over 50 years old are more likely to develop hepatitis, a possible side effect of using ISONIAZID. Older patients should be closely monitored by their doctor whilst using this medication.

Before you start to take it

You must tell your doctor if you are:

• allergic to any other medicines or any foods, dyes or preservatives
• you have any other medical conditions/ health problems, including:
  - lung disease
  - kidney disease
  - liver disease
• you are a heavy drinker
• you are pregnant, intend to become pregnant, are breast-feeding or plan to breastfeed
• have HIV
• Suffer from seizure or fits
• Have numbness and/or tingling of arms or legs (peripheral neuropathy)

Your doctor or pharmacist will discuss the possible risks and benefits of using ISONIAZID during pregnancy and breast-feeding.

If you have not told your doctor about any of the above, tell them before you take any ISONIAZID tablets.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may interfere with ISONIAZID tablets.

These include:

• phenytoin (a medicine used to treat epilepsy)
• carbamazepine (a medicine used to treat epilepsy)
• rifampicin (a medicine used to treat tuberculosis)
• paracetamol (a medicine used to treat pain relief)
• Aluminium hydroxide gel, an antacid used to treat heart burn
• Disulfiram used to treat alcoholism
• Ketoconazole used to treat fungal infections
• Corticosteroids used to treat inflammation
• Diazepam used to treat anxiety and other mental health problems
• Blood thinners used to prevent clots
• Theophyllines used to treat breathing problems

The above medicines may either reduce the effectiveness of ISONIAZID tablets, reduce their own effectiveness and/or react with it resulting in untoward or sometimes dangerous side effects.

This list is not exhaustive. Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking ISONIAZID tablets.

To ensure that the treatment of your condition is effective your doctor will prescribe other medications to be taken over the same time period as ISONIAZID.

If you have any concerns about the interaction of these drugs you should discuss them with your doctor or pharmacist.

How to take it

How much to take

The recommended doses of ISONIAZID tablets are:

Adults: 4 to 5 mg per kg of body weight in divided doses up to a maximum of 300 mg daily. In tuberculous meningitis up to 10 mg per kg of bodyweight may be given daily for the first 1 to 2 weeks of treatment.

Children: 5 to 20 mg per kg of bodyweight daily.

Your doctor will advise you of the correct dose, depending on your weight or the weight of your child.

How to take it

The tablets should be swallowed whole with a glass of water.

How long to take it

It is very important that you continue taking ISONIAZID tablets as long as prescribed by your doctor, even after your symptoms have disappeared. If you do not do this it is very likely that your illness will return.

The treatment of tuberculosis requires long term therapy due to the nature of the bacteria responsible for the illness.

Isoniazid is administered orally.

If symptoms persist, see your doctor.

If you forget to take it

Take your dose as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the dose that you missed.

If you are unsure about whether to take your next dose, speak to your doctor or pharmacist.

Do not try to make up for missed doses by taking more than one dose at a time. This may increase the chance of you getting an unwanted effect.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to casualty at your nearest hospital, if you think that you or anyone else may have taken too much ISONIAZID. Do this even if there are no signs of discomfort or poisoning. Also report any other medicine or alcohol (including any barbiturates or narcotics) which has been taken. You may need urgent medical attention.

Symptoms of overdose include dizziness, nausea, vomiting, sweating, mental confusion, visual disturbances and slurring of speech.

Overdose can lead to coma and seizures.

While you are taking it

Things you must do

Use ISONIAZID tablets exactly as directed or as your doctor has prescribed.

If you are about to be started on any new medicine tell your doctor and pharmacist that you are using ISONIAZID.

Tell your doctor or pharmacist immediately if you feel sick (nauseous), fatigue, tired or generally unwell or have a loss of appetite while taking ISONIAZID.

Tell your doctor if you notice any problems with your eyes while taking ISONIAZID or if you feel that ISONIAZID is not helping your condition.

If you have to have any urine tests tell your doctor you are using this medicine as isoniazid may affect the results of some laboratory tests.

See your doctor regularly. Your doctor needs to check your progress and see whether you need to keep taking ISONIAZID tablets.

Always discuss with your doctor any problems or difficulties during or after taking ISONIAZID tablets.

Things you must not do

Do not take any other medicines while you are taking ISONIAZID tablets without first telling your doctor.

Do not drive or operate machinery until you know how this medicine affects you. It may cause dizziness in some people and therefore may affect alertness.

Do not give this medicine to anyone else, even if his or her symptoms seem similar to yours.

Things to be careful of

Be careful drinking alcohol while taking ISONIAZID tablets. If you drink alcohol, it could make some of the unwanted side effects of ISONIAZID worse.

Your doctor may suggest that you avoid alcohol completely or reduce the amount of alcohol you drink while you are taking ISONIAZID tablets.

Some people may experience side effects such as nausea, vomiting, constipation, drowsiness, dizziness, which may further affect the risk when driving or using dangerous machinery.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking ISONIAZID tablets. This medicine help most people with medical conditions listed in the beginning of this leaflet, but it may have unwanted side effects in some people, especially in elderly patients or those with underlying disorders.

All medicines have side effects. Sometimes they are serious, most of the time they are not.

You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist any questions you may have.

Common side effects

Tell your doctor immediately if you notice any of the following and they worry you:

• jaundice (yellowing of skin)
• nausea (feeling sick)
• vomiting
• dizziness
• drowsiness
• skin rashes
• tiredness
• fever
• pain in arms or legs.
• Enlarged breast tissue in men

Some people may get other side effects of ISONIAZID tablets.

Check with your doctor as soon as possible if you have any problems while taking ISONIAZID tablets even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

After taking it

Storage

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep ISONIAZID tablets in a cool dry place where the temperature stays below 25°C and protect from light.

Do not store it, or any other medicines, in a bathroom or near a sink.

Do not leave it in the car or on windowsills. Heat and dampness can destroy some medicines.

Do not take ISONIAZID if the tablets do not look quite right.

Keep your tablets in the bottle they were provided in until it is time to take them.

Disposal

If your doctor tells you to stop taking this medication or it has passed the expiry date, ask your pharmacist what to do with any tablets that are left over.

Product description

What it looks like

ISONIAZID tablets are white scored tablets and are available in bottles of 100 tablets.

Ingredients

Each ISONIAZID tablet contains 100 mg of isoniazid.

They also contain the following inactive ingredients:

• cellulose-microcrystalline
• silica-colloidal anhydrous
• sodium starch glycollate
• calcium stearate
• gelatin
• propyl hydroxybenzoate
• lactose
• starch-maize
• sodium benzoate
• starch–wheat
• dextrin.

Contains hydroxybenzoate, benzoate, sugars as lactose and gluten.

Sponsor

Arrow Pharma Pty Ltd
15 – 17 Chapel Street
Cremorne Victoria 3121

Australian Registration Number: AUST R 13455.

This leaflet was revised in January 2023.

Published by MIMS March 2023

1 Name of Medicine

Isoniazid.

2 Qualitative and Quantitative Composition

Each tablet contains 100 mg of isoniazid.
Isoniazid exists as colourless, odourless crystals, or white crystalline powder. It is freely soluble in water, sparingly soluble in alcohol, slightly soluble in chloroform, very slightly soluble in ether.

List of excipients with known effect.

3 Pharmaceutical Form

Isoniazid tablets - white scored 100 mg tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of pulmonary and extrapulmonary tuberculosis in combination with other antitubercular agents.

4.2 Dose and Method of Administration

Adults.

Children.

4.3 Contraindications

Patients who develop severe hypersensitivity reactions, including drug induced hepatitis. Previous isoniazid associated hepatic injury; severe adverse reactions to isoniazid, such as drug fever, chills and arthritis; acute hepatic disease of any aetiology. Patients with known hypersensitivity to isoniazid or any of the excipients listed under Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is increased with pre-existing liver disease, age related and concurrent use of other hepatotoxic medications. Approximate case rates by age are: 0/1,000 for people under 20 years of age, 3/1,000 for people in the 20 to 34 year age group, 12/1,000 for people in the 35 to 49 year age group, 23/1,000 for people in the 50 to 64 year age group, and 8/1,000 for people over 65 years of age. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid related hepatitis are not available; however, in a US Public Health Service Surveillance Study of 13,838 people taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Therefore, patients given isoniazid should be carefully monitored and have baseline liver function tests performed and interviewed at monthly intervals. Serum transaminase concentration becomes elevated in about 10 to 20% of patients, usually during the first few months of therapy, but it can occur at any time. Usually, enzyme levels return to normal despite continuance of the drug, but in some cases progressive hepatic dysfunction occurs. Patients should be instructed to report immediately any of the prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since continued use of the drug in these cases has been reported to cause a more severe form of hepatic damage. Patients with tuberculosis should be given appropriate treatment with alternative drugs. If isoniazid must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent hepatic involvement. Preventive treatment should be deferred in people with acute hepatic diseases.
All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If isoniazid therapy must be reinstituted, the drug should be given only after symptoms have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of a recurrent hypersensitivity reaction.
Isoniazid should not be given to patients who have experienced severe adverse reactions including drug-induced liver disease. Care should be taken in giving isoniazid to patients suffering from convulsive disorders, diabetes mellitus and other potentially hepatoxic agents.
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.
Use of isoniazid should be carefully monitored in patients who are receiving phenytoin or carbamazepine concurrently and in patients who are daily users of alcohol (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Susceptibility/ resistance.

Development of drug resistant bacteria.

Ophthalmological examinations.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Since the chemotherapy of tuberculosis involves the use of at least 2 drugs, the possible adverse reactions of each drug should be borne in mind as well as a possible interaction when used concomitantly.
When isoniazid is given to patients who inactivate it slowly or to patients receiving para-aminosalicylic acid concurrently, tissue concentrations may be enhanced, and adverse effects are more likely to appear.
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).

Phenytoin.

Carbamazepine.

Aluminum hydroxide gel.

Cycloserine.

Disulfiram.

Alcohol.

Rifampicin.

Ketoconazole.

Paracetamol.

Benzodiazepines.

Levodopa.

Itraconazole.

Zalcitabine.

Stavudine.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

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.

Nervous system.

Gastrointestinal.

Hepatic*.

Haematological.

Hypersensitivity.

Metabolic and endocrine.

Systemic.

Musculoskeletal and connective tissue disorders.

Psychiatric disorders.

Renal and urinary disorders.

Reproductive system and breast disorders.

Respiratory, thoracic and mediastinal disorders.

Skin and subcutaneous tissue disorders.

Vascular disorders.

Ear and labyrinth disorders.

General disorders and administration site conditions.

Investigations.

Metabolism and nutrition disorders.

Miscellaneous.

Reporting suspected adverse effects.

4.9 Overdose

For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision and visual hallucinations (including bright colours and strange designs) are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe intractable seizures. Severe metabolic acidosis, acetonuria and hyperglycaemia are typical laboratory findings.
Untreated or inadequately treated cases of gross isoniazid overdosage can be fatal. Prompt treatment within the first few hours after drug ingestion has been associated with a good response. The mainstay of treatment is supportive and symptomatic care. Secure the airway and establish adequate respiratory exchange. To control convulsions, administer intravenous short acting barbiturates and intravenous pyridoxine (usually 1 mg/1 mg isoniazid ingested).
Activated charcoal may reduce absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
Obtain blood samples for immediate determination of gases, electrolytes, serum urea, glucose, etc.; type and crossmatch blood in preparation for possible haemodialysis. Rapid control of metabolic acidosis is fundamental to management. Give intravenous sodium bicarbonate at once and repeat as needed, adjusting subsequent dosage on the basis of laboratory findings (i.e. serum sodium, pH, etc.). Forced osmotic diuresis must be started early and should be continued for some hours after clinical improvement to hasten renal clearance of the drug and help prevent relapse; monitor fluid intake and output.
Haemodialysis is advised for severe cases; if this is not available, peritoneal dialysis can be used along with forced diuresis. Along with measures based on initial and repeated determination of blood gases, and on other laboratory tests as needed, utilise meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration pneumonitis, etc.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

The inactive ingredients are: Microcrystalline cellulose, colloidal anhydrous silica, sodium starch glycollate, gelatin, propyl hydroxybenzoate, lactose monohydrate, calcium stearate, maize starch, sodium benzoate, wheat starch, and dextrin.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf-life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light and moisture.

6.5 Nature and Contents of Container

Available in glass bottle of 100's.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Molecular formula: C₆H₇N₃O.
Molecular weight: 137.1.

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes