SUMMARY CMI

ISONIAZID tablets

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ISONIAZID?

Isoniazid contains the active ingredient isoniazid. Isoniazid is used to treat tuberculosis in combination with other anti-tubercular agents.

For more information, see Section 1. Why am I using ISONIAZID? in the full CMI.

2. What should I know before I use ISONIAZID?

Do not use if you have ever had an allergic reaction to isoniazid or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Isoniazid? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Isoniazid and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ISONIAZID?

• The tablet should be swallowed whole with a glass of water.
• 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 10mg 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 body weight daily. Your doctor will advise you of the correct dose, depending on your weight or the weight of your child.

More instructions can be found in Section 4. How do I use ISONIAZID? in the full CMI.

5. What should I know while using ISONIAZID?

For more information, see Section 5. What should I know while using ISONIAZID? in the full CMI.

6. Are there any side effects?

Common side effects include jaundice, nausea, vomiting, dizziness, drowsiness, skin rashes, tiredness, fever, pain in arms or legs and enlarged breast tissue in men.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

ISONIAZID tablets

Active ingredient(s): Isoniazid

Consumer Medicine Information (CMI)

This leaflet provides important information about using Isoniazid. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Isoniazid.

Where to find information in this leaflet:

1. Why am I using Isoniazid?
2. What should I know before I use Isoniazid?
3. What if I am taking other medicines?
4. How do I use Isoniazid?
5. What should I know while using Isoniazid?
6. Are there any side effects?
7. Product details

1. Why am I using ISONIAZID?

Isoniazid contains the active ingredient isoniazid. Isoniazid belongs to a group of medicines called tuberculostatic agents.

Isoniazid is used to treat tuberculosis in combination with other anti-tubercular agents.

2. What should I know before I use ISONIAZID?

Warnings

Do not use ISONIAZID if:

• you are allergic to isoniazid or any of the ingredients listed at the end of this leaflet.
• Always check the ingredients to make sure you can use this medicine.
• 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.

Check with your doctor if you:

• have any other medical conditions.
• take any medicine for any other condition.
• 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 doctors whilst using this medication.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins, or supplements that you buy without a prescription from your 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)
• Aluminum 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.
• Theophylline 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 medication to be taken over the same time as ISONIAZID.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ISONIAZID.

4. How do I use ISONIAZID?

How much to take / use

• 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 10mg 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 body weight daily. Your doctor will advise you of the correct dose, depending on your weight or the weight of your child.
• The tablet should be swallowed whole with a glass of water.

If you forget to use ISONIAZID

ISONIAZID should be used regularly at the same time each day. If you miss your dose at the usual time, take your dose as soon as you remember, and then go back to taking it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

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

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

Do not try to make up for missed doses by taking more than one dose at a time.

This may increase the chance of getting an unwanted side effect.

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

If you use too much ISONIAZID

If you think that you have used too much ISONIAZID, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre
  (by calling 13 11 26), or
• contact your doctor, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using ISONIAZID?

Things you should do

Call your doctor straight away if you:

• 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 that you are using this medicine as isoniazid may affect the results if 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.

Remind any doctor, dentist, or pharmacist you visit that you are using ISONIAZID.

Things you should not do

• Do not take any other medicines while you are taking ISONIAZID tablets without first telling your doctor.
• Do not give this medicine to anyone else, even if his or her symptoms seem like you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ISONIAZID affects you.

ISONIAZID may cause dizziness in some people and therefore may affect alertness.

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

Drinking alcohol

Tell your doctor if you drink alcohol.

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.

Looking after your medicine

• Follow the instructions in the carton on how to take care of your medicine properly.
• Do not take ISONIAZID if the tablets do not look quite right.
• Keep ISONIAZID tablets in a cool dry place where the temperature stays below 25°C and protect from light.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

• in the bathroom or near a sink, or
• in the car or on windowsills.
• Heat and dampness can destroy medicines.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half meters above the ground is a good place to store medicines.

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

When to discard your medicine (as relevant)

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.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

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.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What ISONIAZID contains

Contains hydroxybenzoate, benzoate, sugars as lactose and gluten.

Do not take this medicine if you are allergic to any of these ingredients.

What ISONIAZID looks like

Isoniazid tablets are white scored tablets and are available in bottles of 100 tablets. (Aust R 13455).

Who distributes ISONIAZID

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne Victoria 3121

This leaflet was prepared in November 2023.

Published by MIMS December 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