Consumer medicine information

Insig

Indapamide hemihydrate

BRAND INFORMATION

Brand name

Insig

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Insig.

SUMMARY CMI

INSIG

Consumer Medicine Information (CMI) summary

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

1. Why am I taking INSIG?

INSIG contains the active ingredient indapamide hemihydrate active ingredient indapamide which belongs to a group of medicines called chlorosulfamoyl diuretics (a type of “fluid” or “water” tablet). INSIG is used to treat high blood pressure (also known as hypertension).

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

2. What should I know before I take INSIG?

Do not take if you have ever had an allergic reaction to indapamide hemihydrate 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 take INSIG? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with indapamide 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 take INSIG?

  • Swallow tablet(s) with a glass of water. Do not crush or chew the tablets.

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

5. What should I know while taking INSIG?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking this medicine.
  • If you become pregnant or start to breastfeed while taking this medicine, tell your doctor immediately.
  • Make sure you drink enough water during exercise and hot weather especially if you sweat a lot. This will help you avoid any dizziness or light-headedness caused by a sudden drop in blood pressure.
  • Tell your doctor immediately if you notice any serious side effects, especially severe nausea or vomiting or stomach pain.
Things you should not do
  • Do not give this medicine to anyone else, even if they have the same condition as you.
  • Do not take this medicine to treat other complaints unless your doctor tells you to.
  • Do not stop taking this medicine or change the dosage, without checking with your doctor.
  • Is not recommended for use in children.
Driving or using machines
  • Take care when driving or operating machinery until you know how this medicine affects you.
  • Dizziness or weakness due to low blood pressure may occur in certain patients. If you have any of these symptoms do not drive or operate machinery.
Drinking alcohol
  • Tell your doctor if you drink alcohol. Be careful when drinking alcohol while you are taking this medicine. Dizziness or light-headedness may be worse if you drink alcohol.
Looking after your medicine
  • Store below 25°C. Store in original carton. Keep your tablets in the blister pack until it is time to take them.

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

6. Are there any side effects?

There are a number of side effects associated with INSIG. It is important to be aware of them so that you can identify any symptoms if they occur.

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

INSIG

Active ingredient(s): indapamide hemihydrate

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I taking INSIG?

INSIG contains the active ingredients indapamide hemihydrate.

INSIG is used to treat high blood pressure (also known as hypertension).

Everyone has blood pressure. This pressure helps to circulate blood all around the body. Your blood pressure may be different at different times of the day, depending on how busy or stressed you are.

You have high blood pressure (hypertension) when your blood pressure stays higher than is needed, even when you are calm and relaxed.

If high blood pressure is not treated, it can lead to serious health problems. You may feel fine and have no symptoms, but eventually it can cause stroke, heart disease and kidney failure.

INSIG helps to lower your blood pressure.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed this medicine for another reason.

There is no evidence that this medicine is addictive.

2. What should I know before I take INSIG?

Warnings

Do not take INSIG if:

You have or have had any of the following medical conditions:

  • You are allergic to indapamide hemihydrate, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • Sulphonamide (sulfa) antibiotics, thiazide diuretics (a type of "fluid" or "water" tablet).
  • You are intolerant or allergic to lactose. This medicine contains lactose.
  • You have or have had any of the following medical conditions:
  • have severe kidney disease.
  • You have severe liver disease or suffer from a condition called hepatic encephalopathy (liver problems which affect the brain and central nervous system).
  • You have low potassium levels in your blood.
  • You are pregnant or trying to become pregnant. This medicine may affect your developing baby if you take it during pregnancy.
  • You are breastfeeding or intend to breastfeed. This medicine may pass into human breast milk.
  • The packaging is torn or shows signs of tampering, or the tablets do not look quite right.
  • The expiry date (EXP) on the pack has passed.

Tell your doctor straight away if:

  • You have an intolerance to lactose monohydrate.
  • You have or have had any other health problems, including:
  • High or low levels of potassium, sodium, or other problems with salt balance.
  • Gout.
  • Diabetes.
  • Increased sensitivity to sunlight (photosensitivity reactions).
  • Systemic lupus erythematosus (a disease affecting the skin, joints and kidneys).
  • Heart rhythm problems.
  • Problems with your kidneys.
  • If you experience a decrease in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye or an increase of pressure in your eye and can happen within hours to a week of taking INSIG. This can lead to permanent vision loss, if not treated. If you earlier have had a penicillin or sulfonamide allergy, you can be at higher risk of developing this.
  • You have muscle disorders including muscle pain, tenderness, weakness or cramps.
  • A test to check how well your parathyroid gland is working.
  • Athletes should be aware that this medicine contains an active ingredient, which may give a positive reaction in doping tests.
  • You are pregnant or plan to become pregnant or are breastfeeding. Do not take this medicine whilst pregnant or breastfeeding.

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

Pregnancy and breastfeeding

Do not take this medicine if you are pregnant or plan to become pregnant.

Do not take this medicine if you are breastfeeding or plan to breastfeed.

It is important to tell your doctor if you are pregnant or intend to become pregnant, or 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.

You should not take INSIG with lithium medications (used to treat mood swings and some types of depression due to the risk of increased levels of lithium in the blood.

Some medicines may interfere with INSIG and affect how it works. These include:

  • Some steroid medicines.
  • Diuretics (sometimes called “fluid” or “water” tablets, e.g. amiloride, spironolactone, triamterene).
  • Medicines used for heart rhythm problems (e.g. disopyramide, amiodarone, sotalol, flecainide).
  • Some medications used to treat high blood pressure (e.g. angiotensin converting enzyme (ACE) inhibitors), a fast or irregular heartbeat and other heart conditions.
  • Medicines to treat mental illnesses such as some medicines for epilepsy, anxiety, schizophrenia and some antidepressants (e.g. tricyclic antidepressants, antipsychotic drugs, neuroleptics such as: droperidol, haloperidol, chlorpromazine, trifluoperazine, amisulpride, sulpiride, psychoanaleptics e.g. donepezil).
  • Antiparasitic medicines used to treat certain types of malaria (e.g. chloroquine).
  • Pentamidine (a medicine used to treat certain types of pneumonia).
  • Antihistamines used to treat allergic reactions, such as hay fever.
  • Medicines used to treat nausea and vomiting (e.g. ondansetron, domperidone).
  • Medicines used to treat cancer (e.g. vandetanib, oxaliplatin).
  • Anaesthetics (e.g. propofol, sevoflurane).
  • Anagrelide (used to reduce elevated blood platelet counts).
  • Non-steroidal anti-inflammatory drugs for pain relief (e.g. ibuprofen) or high doses of aspirin.
  • Calcium supplements.
  • Stimulant laxatives.
  • Baclofen (a medicine used to treat muscle stiffness occurring in diseases such as multiple sclerosis).
  • Metformin (a medicine used to treat diabetes).
  • Ciclosporin, tacrolimus (medicines used to treat certain problems with the immune system).
  • Medicines used to treat fungal infections (e.g. Amphotericin B (amphotericin) by IV, fluconazole).
  • Medicines used during scans to see the images of your body.
  • Medicines used to treat gastro-intestinal problems (e.g. cisapride, papaverine).
  • Medicines used to treat bacterial infections (e.g. Moxifloxacin, ciprofloxacin, clarithromycin, erythromycin by IV).
  • Allopurinol (used to treat gout).
  • Tetracosactide (tetracosactrin) (to treat Crohn's disease).
  • Methadone (used to treat addiction).
  • Cilostazol (used to treat cramp-like pain in the legs when you walk).
  • These medicines may be affected by INSIG or may affect how well it works.

If you are taking any of these, you may need a different dose, or you may need to take different medicines.

Other medicines not listed above may also interfere with INSIG.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

4. How do I take INSIG?

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

When to take INSIG

Take it at about the same time each day, preferably in the morning. Taking it at the same time each day will have the best effect and will also help you remember when to take it.

How to take INSIG

Swallow your tablet(s) with a glass of water. Do not crush or break the tablets.

If you forget to take INSIG

If your next planned dose is less than 6 hours away, leave out the dose that you missed. Take the next dose at the usual time and continue as normal.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

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

This may increase the chance of you experiencing side effects.

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

How long to take it

INSIG can help to control your blood pressure but cannot cure this condition. INSIG treatment is usually for life, so you should keep taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

If you take too much INSIG

If you think that you have taken too much INSIG, 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.

If you take too much INSIG, your blood pressure may drop (hypotension) or you may be sick, feel confused, or have kidney problems or changes in the salt and water content of your body or muscle cramps. You may require urgent medical attention.

5. What should I know while taking INSIG?

Things you should do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking this medicine.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant or start to breastfeed while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all your doctor's appointments so that your progress can be checked.

Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Make sure you drink enough water during exercise and hot weather especially if you sweat a lot. This will help you avoid any dizziness or light-headedness caused by a sudden drop in blood pressure.

Call your doctor straight away if you:

  • Notice any serious side effects, especially severe nausea or vomiting or stomach pain.

Remind any doctor, dentist or pharmacist you visit that you are taking INSIG.

Things you should not do

  • Do not take this medicine to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking your medicine or change the dosage without checking with your doctor.

Driving or using machines

Be careful when driving or operating machinery until you know how this medicine affects you. Dizziness or weakness due to low blood pressure may occur in certain patients. If you have any of these symptoms do not drive or operate machinery.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while you are taking this medicine. Dizziness or light-headedness may be worse if you drink alcohol.

Things to be careful of

You may feel light-headed or dizzy when you begin to take this medicine. This is because your blood pressure is falling. If you have these symptoms when standing up or getting out of bed, then getting up more slowly can help. This allows your body to get used to the change in position and blood pressure. If you have these symptoms and they do not get better in a short time, then talk to your doctor.

INSIG contains a drug substance which may give a positive result in doping tests.

Looking after your medicine

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the blister pack they may not keep well. A locked cupboard at least one-and-a half meters above ground is a good place to store medicines. Heat and dampness can destroy some medicines.

Follow the instructions on the carton on how to take care of your medicine properly.

Keep your medicine in a cool dry place where the temperature will stay below 25°C. Do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

When to discard your medicine

Do not take this medicine after the expiry date.

Getting rid of any unwanted medicine

If your doctor tells you to stop taking INSIG, or the tablets have passed their expiry date, return any leftover tablets to your pharmacist for disposal.

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.

INSIG helps most people with high blood pressure, but it may sometimes have unwanted side effects in a few people. While these side effects when they occur are usually mild they can be serious.

Less serious side effects

Less serious side effectsWhat to do
  • Headache.
  • Feeling tired or as if you have less energy, difficulty sleeping.
  • Feeling faint, light-headed, or dizzy.
  • Feeling nervous or anxious.
  • Feeling sick or having an upset stomach, having an uncomfortable feeling after eating, vomiting, constipation, diarrhoea or loss of appetite.
  • Muscle weakness, pain, tenderness, back pain, joint pain, cramp or tingling or numbness of the hands or feet (and particularly if at the same time you feel unwell or have a high temperature it may be caused by an abnormal muscle breakdown (not known)).
  • Skin rashes or other allergic reactions.
  • Gout.
  • Increased sensitivity to sunlight.
  • An increased risk of becoming dehydrated (in elderly patients and in patients with heart failure).
  • Low blood levels of potassium, magnesium or chlorine.
  • Kidney disease.
  • Inflammation of the pancreas.
  • Hepatic encephalopathy (liver problems which affect the brain and central nervous system).
  • Abnormal liver function.
  • If you suffer from systemic lupus erythematosus (a type of collagen disease), this might get worse.
  • Changes in blood cells, such as thrombocytopenia (a decrease in the number of platelets which causes easy bruising and nasal bleeding), leucopoenia (a decrease of white blood cells which may cause unexplained fever, soreness of the throat or other flu-like symptoms) and anaemia (a decrease in red blood cells).
  • Low blood pressure, unusual heartbeat.
  • High level of calcium in blood.
  • Blurred or changed vision, short sightedness (myopia).
  • Decrease in vision or pain in your eyes due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye or acute angle-closure glaucoma).
  • Dry mouth.
  • Cystitis.
  • Erectile dysfunction.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • Swelling of your lips, face, mouth, tongue or throat.
  • Purple spots with occasional blisters on the front of your arms and legs and/or around your neck and ears. (A rare condition known as Stevens-Johnson Syndrome).
  • Toxic epidermal necrolysis.
  • A fast and irregular heartbeat.
  • Severe blisters, skin rash, itching or other allergic reactions.
STOP TAKING THIS MEDICINE. Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these 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.

Changes may occur in your laboratory parameters (blood tests) and your doctor may need to give you blood tests to check your condition. The following changes in laboratory tests may occur low potassium in the blood, low sodium in the blood, low sodium in the blood (that may lead to dehydration and low blood pressure), increase in uric acid (a substance which may cause or worsen gout), increase in blood glucose levels in diabetic patients, increased levels of liver enzymes.

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 INSIG contains

Active ingredient
(main ingredient)
  • Each tablet contains 2.5 mg of indapamide hemihydrate.
Other ingredients
(inactive ingredients)
  • acasia
  • calcium carbonate
  • lactose monohydrate
  • magnesium stearate
  • maize starch
  • povidone
  • purified talc
  • sucrose
  • titanium dioxide
  • OPAGLOS tablet core sealant product OPAGLOS 6000P OFF-WHITE
  • OPASEAL Pharmaceutical Enteric - Phthalavin (Pvap) Solution P-2-0300G Clear
Potential allergens
  • Lactose

This medicine is free from gluten, sucrose, tartrazine and other azo dyes.

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

What INSIG looks like

White, biconvex, sugar-coated tablets.

AUST R 184244.

Available in blister packs of 60 or 90 tablets.

Who distributes INSIG

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel St
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was prepared in March 2025.

Published by MIMS May 2025

BRAND INFORMATION

Brand name

Insig

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

1 Name of Medicine

Indapamide hemihydrate.

2 Qualitative and Quantitative Composition

Excipients with known effect.

Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Each tablet contains 2.5 mg indapamide hemihydrate. Insig are white, biconvex, sugar coated tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Management of essential hypertension. It may be tried as a sole therapeutic agent in the treatment of mild to moderate hypertension. Normally Insig is used as the initial agent in multiple drug regimens.

4.2 Dose and Method of Administration

Adults.

1 tablet (indapamide 2.5 mg) to be taken daily, by oral route in the morning. The action of Insig is progressive and whilst the optimum reduction in blood pressure is usually seen after four weeks, a further small but useful reduction in blood pressure may be observed over the following four to six weeks. A larger dose than 1 tablet (2.5 mg) of Insig daily is not recommended as there is little additional antihypertensive effect, whilst the diuretic effect becomes more pronounced.
A single tablet of Insig may effectively be combined with the following antihypertensive agents: β-blockers, methyldopa sesquihydrate, clonidine, prazosin and angiotensin converting enzyme (ACE) inhibitors.
Combination with a diuretic agent is not recommended as significant electrolyte disturbances may occur.
Indapamide has a slight but significant carry-over hypotensive effect lasting up to one to two weeks after treatment is stopped.

4.3 Contraindications

Severe renal failure, anuria, progressive and severe oliguria.
Hepatic coma, hepatic encephalopathy or severe impairment of liver function.
Known hypersensitivity to indapamide, other sulfonamide derivatives or any of the excipients (see Section 6.1 List of Excipients).
Hypokalaemia.

4.4 Special Warnings and Precautions for Use

Electrolyte changes observed with indapamide become more pronounced at doses above 2.5 mg/day. The daily maximum recommended dose of indapamide is 2.5 mg administered as one tablet, since doses above 2.5 mg only increase the diuretic effect and electrolyte disturbances consequent to diuresis without any further appreciable antihypertensive effect.
Hypokalaemia may occur at all doses. Symptoms of hypokalaemia include weakness, cramps, and cardiac dysrhythmias. Hypokalaemia is a particular hazard in patients treated with digoxin as; dangerous or fatal arrhythmias may be precipitated. Although Insig can be safely administered to hypertensive patients with renal impairment, caution should be observed when it is administered to patients with severe renal impairment. In this case the unchanged drug is excreted primarily by the renal route, and plasma concentrations are elevated (see Section 5.2 Pharmacokinetic Properties).

Hepatic encephalopathy.

When liver function is impaired, thiazide-related diuretics may cause, particularly in case of electrolyte imbalance, hepatic encephalopathy which can progress to hepatic coma. Administration of the diuretic must be stopped immediately if this occurs.

Uric acid.

Hyperuricaemia may occur during administration of indapamide. Rarely gout has been reported. Tendency to gout attacks may be increased in patients with hyperuricaemia.

Lithium.

Diuretics should not be given with lithium because they reduce its renal clearance and add a high risk of lithium toxicity (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Photosensitivity.

Cases of photosensitivity reactions have been reported with thiazides and thiazide-related diuretics. It is recommended to stop treatment if a photosensitivity reaction occurs during treatment. If re-administration of the diuretic is deemed necessary, it is recommended that areas exposed to the sun or to artificial UVA are protected.

Lactose intolerance.

Insig tablets contain lactose monohydrate. Patients with an intolerance to lactose, rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Water and electrolyte balance.

Patients receiving indapamide should be monitored for signs and symptoms of fluid or electrolyte imbalance; namely hyponatraemia, hypochloraemia and hypokalaemia. Blood urea, nitrogen and uric acid should be assessed during therapy.
The signs of electrolyte imbalance are dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscle fatigue, hypotension, oliguria, gastrointestinal disturbances such as nausea and vomiting, tachycardia and ECG changes.

Plasma sodium.

This must be measured before starting treatment, then subsequently at regular intervals. The decrease in plasma sodium may initially be asymptomatic. Regular monitoring is therefore essential and should be more frequent in the elderly and in patients with cirrhosis (see Section 4.8 Adverse Effects (Undesirable Effects)). Treatment with any diuretic may cause hyponatraemia, sometimes with very serious consequences. Hyponatraemia with hypovolaemia may be responsible for dehydration and orthostatic hypotension. Concomitant loss of chloride ions may lead to secondary compensatory metabolic alkalosis.

Plasma potassium.

Potassium depletion with hypokalaemia is the major risk of thiazide and related diuretics. Hypokalaemia may cause muscle disorders. Cases of rhabdomyolysis have been reported, mainly in the context of severe hypokalaemia. The risk of onset of hypokalaemia (< 3.4 mmol/L) must be prevented in certain high-risk populations, i.e. the elderly, malnourished and/or polymedicated, cirrhotic patients with oedema and ascites, and patients with coronary artery disease and/or heart failure. In these patients, hypokalaemia increases the cardiac toxicity of digitalis preparations and increases the risk of arrhythmias.
Hypokalaemia will be more common when combined with a steroid or adrenocorticotropic (ACTH) treatment and when electrolyte intake is inadequate.
Individuals with a long QT interval, whether the origin is congenital or iatrogenic, are also at increased risk as hypokalaemia and bradycardia, are predisposing factors to the onset of severe arrhythmias, in particular, potentially fatal torsades de pointes.
Plasma potassium should be measured in the first week of treatment. More frequent monitoring of plasma potassium is required in all the situations indicated above.
Hypokalaemia, if detected, should be corrected. Hypokalaemia found in association with low serum magnesium concentration can be refractory to treatment unless serum magnesium is corrected.

Plasma magnesium.

Thiazides and related diuretics have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Plasma calcium.

Diuretic treatment should be withdrawn before the investigation of parathyroid function. Thiazide and related diuretics may decrease urinary calcium excretion and cause a slight and transitory rise in calcium. Frank hypercalcaemia may be due to previously unrecognised hyperparathyroidism.
Orthostatic hypotension may occur and may be potentiated by alcohol, barbiturates, narcotics or concurrent therapy with other antihypertensives.
When Insig is combined with other nondiuretic antihypertensive medicines, the effects on blood pressure are additive.
Sulfonamide derivatives have been reported to exacerbate or activate systemic lupus erythematosus. Serious allergic skin reactions (such as Stevens-Johnson syndrome) have also occasionally been reported to be associated with sulfonamides. These possibilities should be kept in mind with the use of indapamide.
Although an Insig dose of one 2.5 mg tablet/day can be used safely in patients with hypertension and renal impairment, treatment should be discontinued if there is an increase in azotaemia and oliguria.
Studies in functionally anephric patients for one month undergoing chronic haemodialysis have not shown evidence of drug accumulation, despite the fact that indapamide is not dialysable. A study in patients with impaired renal function demonstrated that patients with severe renal impairment (creatinine clearance 11-35 mL/min) had impaired clearance of indapamide and elevated plasma levels of the drug.

Blood glucose.

Monitoring of blood glucose is important in patients with diabetes, in particular in the presence of hypokalaemia.

Athletes.

Insig contains indapamide which may give a positive reaction in doping tests.

Choroidal effusion, acute myopia and secondary angle-closure glaucoma.

Sulfonamide, or sulfonamide derivative, drugs can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue drug intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Use in the elderly.

In the elderly, the plasma creatinine must be adjusted in relation to age, weight and gender. Elderly patients can be treated with Insig when renal function is normal or only minimally impaired.

Paediatric use.

Safety and effectiveness have not been established.

Effects on laboratory tests.

Hyperuricaemia (0.4%). Hyperglycaemia (0.4%) (see Section 4.8 Adverse Effects (Undesirable Effects)).
The following values represent the maximum variations from pre-treatment values in occasional patients at some stage during, but not necessarily throughout, treatment: blood uric acid up 8.6%, blood glucose up 6%, BUN up 5.7%, blood creatinine up 3.6%.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Potential interactions may occur with lithium, digoxin, alcohol, narcotics and barbiturates; see Section 4.4 Special Warnings and Precautions for Use for further information.
No interactions have been reported between indapamide and anticoagulants, or between indapamide and uricosuric medicines.
It is recommended that the drug not be used in combination with a diuretic agent since the combination may produce hypokalaemia and hyperuricaemia.

Combined use which is not recommended.

Lithium.

The combined use of Insig and lithium may result in increased plasma lithium levels and produce symptoms of overdose (due to decreased urinary lithium excretion). If diuretics are necessary, careful monitoring of plasma lithium and dose adjustment are required.

Combined use which requires special care.

Torsades de pointes-inducing drugs.

The combined use of Insig and torsades de pointes-inducing drugs, including the following, is not recommended due to the increased risk of ventricular arrhythmias, particularly torsades de pointes (hypokalaemia is a risk factor). Medicines which induce torsades de pointes include (but are not limited to):
class Ia antiarrhythmics (e.g. disopyramide) and class Ic antiarrhythmic agents (e.g. flecainide);
class III antiarrhythmics (e.g. amiodarone, sotalol);
some antipsychotics: phenothiazines (e.g. chlorpromazine, trifluoperazine), benzamides (e.g. amisulpride, sulpiride), butyrophenones (e.g. droperidol, haloperidol) and other antipsychotics;
psychoanaleptic (e.g. donepezil);
some antidepressants (e.g. citalopram, escitalopram);
antimicrobial agents: fluoroquinolones (e.g. moxifloxacin, ciprofloxacin), macrolides (e.g. erythromycin IV, clarithromycin), azole antifungals (e.g. fluconazole);
antiparasitics (e.g. chloroquine, pentamidine);
antihistamines;
antiemetics (e.g. ondansetron, domperidone);
antineoplastic and immunomodulating agents (e.g. vandetanib, oxaliplatin, anagrelide);
anaesthetics (e.g. propofol, sevoflurane);
others: diphemanil, methadone, papaverine, cilostazol.
This list is indicative and not exhaustive.
Monitor (using plasma electrolytes and ECG) for hypokalaemia and correct, if required, before using Insig and a torsades de pointes-inducing drug in combination.

NSAIDs (systemic route) including COX-2 selective inhibitors, high dose salicylic acid (≥ 3 g/day).

Due to the risk of acute renal failure in patients with dehydration as a result of decreased glomerular filtration, it is recommended that hydration and renal function be monitored at the start of treatment. Combined use with NSAIDs may also result in a reduction in the antihypertensive effect of Insig.

ACE inhibitors.

Combined use with ACE inhibitors in the presence of pre-existing sodium depletion (particularly in patients with renal artery stenosis) may increase the risk of sudden hypotension and/or acute renal failure.
In patients with hypertension when prior diuretic treatment may have caused sodium depletion, it is necessary to either:
stop the diuretic three days before starting treatment with the ACE inhibitor, and restart a hypokalaemic diuretic if necessary; or
give low initial doses of the ACE inhibitor and increase the dose gradually.
In patients with congestive heart failure, initiation with a very low dose of ACE inhibitor, possibly after a reduction in the dose of the hypokalaemic diuretic, is recommended.
The monitoring of renal function (plasma creatinine) during the first weeks of treatment with an ACE inhibitor is recommended in all patients.

Other compounds causing hypokalaemia: amphotericin B (amphotericin) (IV), gluco- and mineralocorticoids (systemic route), stimulant laxatives.

Due to the increased risk of hypokalaemia (additive effect):
monitoring, and correction if required, of plasma potassium (especially during treatment with digoxin) is recommended;
the use of non-stimulant laxatives is recommended.

Baclofen.

Due to the increased risk of antihypertensive effects, it is recommended that hydration and renal function be monitored at the start of treatment.

Digitalis preparations.

Monitoring of plasma potassium, plasma magnesium and ECG is recommended during treatment with digitalis, and if necessary, adjust the treatment as hypokalaemia and/or hypomagnesaemia predispose to the toxic effects of digitalis.

Allopurinol.

Combined use with indapamide may increase the incidence of hypersensitivity reactions to allopurinol.

Combinations to be taken into consideration.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene).

Due to the increased risk of either hyperkalaemia or hypokalaemia (particularly in patients with renal failure or diabetes), care should be taken when co-administering potassium-sparing diuretics. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.

Metformin.

Do not co-administer with metformin when plasma creatinine exceeds 15 mg/L (135 micromol/L) in men and 12 mg/L (110 micromol/L) in women due to the increased risk of metformin induced lactic acidosis as a result of the possibility of functional renal failure associated with diuretics and more particularly with loop diuretics.

Iodinated contrast media.

Adequate hydration before administration of the iodinated compound is recommended due to an increased risk of acute renal failure resulting from dehydration, particularly when large doses of iodinated contrast media are used.

Imipramine-like antidepressants, neuroleptics.

Caution is recommended with these combinations due to an increased antihypertensive effect and increased risk of orthostatic hypotension.

Calcium (salts).

Caution is recommended with this combination due to the risk of hypercalcaemia resulting from decreased urinary elimination of calcium.

Ciclosporin, tacrolimus.

Caution is recommended with this combination due to the risk of increased plasma creatinine without any change in circulating ciclosporin levels, even in the absence of water/sodium depletion.

Corticosteroids, tetracosactide (tetracosactrin) (systemic route).

Caution is recommended with this combination due to the risk of decreased antihypertensive effect (water/sodium retention due to corticosteroids).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A reproductive toxicity study in rats showed no impairment of male or female fertility at oral indapamide doses up to 25 mg/kg/day, however, the number of implantation sites was reduced at the highest dose.
(Category C)
Indapamide should be avoided in pregnant women and should not be used to treat oedema in pregnancy. There are limited data with the use of indapamide in pregnant women. Prolonged exposure to thiazides during the third trimester of pregnancy can reduce maternal plasma volume as well as uteroplacental blood flow, which may cause foetal-placental ischaemia and growth retardation.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Thiazides, related diuretics and loop diuretics enter the foetal circulation and may cause electrolyte disturbances. Neonatal thrombocytopenia has been reported with thiazides and related diuretics. Loop diuretics like furosemide (frusemide) and bumetanide are probably also associated with this risk. During the latter part of pregnancy products of this type should only be given on sound indications, and then in the lowest effective dose.
 Indapamide should not be used during breast-feeding. Indapamide is excreted in human breast milk and the possible effect on the newborn is unknown and cannot be excluded. Indapamide is closely related to thiazide diuretics which have associated with a decrease in, or even suppression of, lactation. Hypersensitivity to sulfonamide-derived medicines and hypokalaemia might occur.

4.7 Effects on Ability to Drive and Use Machines

Indapamide does not affect vigilance but different reactions related to a decrease in blood pressure may occur in individual cases, especially at the start of treatment or when another antihypertensive agent is added. Treatment with any blood pressure lowering agent may, therefore, affect the ability to drive, cross the road safely or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

In general, most adverse effects are mild and transient. The most frequently reported are: hypersensitivity reactions, mainly dermatological (in subjects with a predisposition to allergic and asthmatic reactions and macropapular rashes), asthenia, dizziness, headache, fatigue, muscle cramps, and gastrointestinal disturbances, usually occurring within the first month of treatment.
During clinical trials, hypokalaemia (plasma potassium < 3.4 mmol/L) was seen in 25% of patients and < 3.2 mmol/L in 10% of patients after four to six weeks treatment. After 12 weeks treatment, the mean fall in plasma potassium was 0.41 mmol/L. Hypochloraemia 9.4%; hyponatraemia 3.1%.
The majority of adverse reactions concerning clinical or laboratory parameters are dose-dependent. Other adverse reactions have been nonspecific. Cutaneous rash and impotence have been occasionally reported. Percentages shown below indicate the incidence in clinical trials.
The following adverse effects have been observed with indapamide during treatment ranked according to the following frequencies: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). See Table 1.
Other adverse reactions, reported in clinical studies with the immediate release formulation of indapamide include the following:

Central nervous system.

Lethargy.

Gastrointestinal.

Anorexia, gastralgia, diarrhoea.

Metabolism and nutrition disorders.

Hypochloraemia, hyponatraemia.

Musculoskeletal.

Joint pain, back pain, weakness of legs.

Cardiac disorders.

Tachycardia, ECG changes (nonspecific ST-T changes, U waves, left ventricular strain).

Vascular disorders.

Orthostatic hypotension.

Urogenital.

Modification of libido, polyuria.

Endocrine.

Gout.

Other.

Tinnitus, malaise/fainting, sweat.

Laboratory abnormalities.

BUN increase, blood creatinine increase.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of this medicinal product is important. It allows continued monitoring of the benefit-risk balance of this medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at https://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Signs of acute poisoning at higher doses take the form of water/electrolyte disturbances (hyponatraemia, hypokalaemia) and may include the possibility of nausea, vomiting, hypotension, cramps, vertigo, drowsiness, confusion, polyuria or oliguria possibly to the point of anuria (by hypovolaemia). In patients with cirrhosis, an overdose might precipitate hepatic coma.

Treatment.

There is no specific antidote. Treatment is symptomatic and supportive. Discontinue drug; induce emesis or perform gastric lavage and/or administration of activated charcoal (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), correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Indapamide is an oral antihypertensive agent. The mechanism whereby indapamide exerts its antihypertensive action has not been completely elucidated; both vascular and renal actions have been implicated.
At a dose of 2.5 mg the renal effects of indapamide are minimal and the antihypertensive effect of indapamide has been attributed to a reduction in vascular reactivity to pressor amines. The finding that indapamide retains its antihypertensive activity in functionally anephric patients lends support to the hypothesis. The renal site of action of indapamide is the proximal segment of the distal tubule. Indapamide appears to have natriuretic properties (sodium and chloride being excreted in equivalent amounts) with less effect on kaliuresis or uric acid excretion. Only at doses greater than 2.5 mg/day is an appreciable increase in urinary volume observed in humans. No significant changes in plasma sodium levels have been observed in clinical studies. Significant hypokalaemia (plasma potassium < 3.2 mmol/L) has been reported in some 10% of patients.
Indapamide (2.5 mg daily) does not adversely affect serum triglycerides, LDL cholesterol, the LDL-HDL cholesterol ratio, or glucose tolerance.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Possibly related to its high lipid solubility, absorption of indapamide from the gastrointestinal tract is rapid (within 0.5 to 1 hour after an oral dose) and complete. Bioavailability of the tablet formulation is 100% and is virtually unchanged with food or antacids.

Distribution.

Indapamide is widely distributed throughout the body, with extensive binding to specific sites. In blood, it is highly bound to red blood cells (80%) and, more specifically, to carbonic acid anhydrase (98%) without having any significant inhibiting activity on this enzyme.
In plasma, it is relatively highly bound to plasma proteins (79%). It is also taken up to a significant degree in the vascular compartment, the drug has a relatively low apparent volume of distribution (approximately 60 L), and 40% of the dose is located in the blood one hour after administration.

Metabolism and excretion.

After a single oral dose of 2.5 mg, as well as after repeated administration of 2.5 mg daily for 15 days, plasma elimination half-life of unchanged indapamide is biphasic with half-lives of 14 and 25 hours, indicating that once daily dosing is possible and that no change in kinetics occurs after repeated dosing. Both single and multiple dose data indicate that indapamide's kinetics are linear. Steady-state plasma levels are reached within three to four days after starting treatment, and the drug does not accumulate in hypertensive patients with various degrees of renal insufficiency.
Indapamide is extensively metabolised in the liver.
Following radioactivity studies using carbon-14, the main route of elimination is the urine, but only 5% to 7% of the dose is excreted into the urine as unchanged drug; 20% to 23% of total radioactivity is eliminated into the faeces. Renal clearance of indapamide (as unchanged drug) is approximately 5 mL/minute, representing less than 10% of systemic clearance. The high lipid solubility of the indoline moiety confers to indapamide its highly localised binding to structures in the cardiovascular system.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

Carcinogenicity studies in mice and rats showed no evidence of tumourigenicity when indapamide was administered in the diet at levels up to 100 mg/kg/day.

Mutagenicity.

Indapamide was negative in mutagenicity tests in bacteria, and bone marrow micronucleus tests in mice. There was a decrease in weight gain of the F1 generation from rats treated orally at 2.5 mg/kg/day. Galactopoiesis was affected in the F1 generation from rats treated orally at 0.5 mg/kg/day and this led to increased mortality of the F2 generation during the first 48 hours of life. No embryo-foetal toxicity or teratogenic potential were seen in rats (up to 150 mg/kg/day) and in rabbits (up to 180 mg/kg/day).

6 Pharmaceutical Particulars

6.1 List of Excipients

Acacia, calcium carbonate, lactose monohydrate, magnesium stearate, maize starch, Opaglos tablet core sealant product Opaglos 6000P Off-white, Opaseal Pharmaceutical Enteric - Phthalavin (Pvap) Solution P-2-0300G clear, povidone, purified talc, sucrose, titanium dioxide.

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

Insig are available in PVC/PVDC/Aluminium blisters of 60 and 90 tablets.

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

Indapamide hemihydrate (4-chloro-N-(2-methyl-1-indolinyl)-3- sulfamoyl benzamide hemihydrate) is a non-thiazide indole derivative of chlorosulfonamide. It is a white crystalline lipophilic powder, soluble in methanol, ethanol, acetic acid and ethyl acetate; very slightly soluble in ether, chloroform and benzene and practically insoluble in water.

Chemical structure.


Chemical name: 4-chloro-N-(2-methyl-1- indolinyl)-3- sulfamoyl benzamide hemihydrate.
Molecular weight: 374.85.
Molecular formula: C16H16ClN3O3S, ½H2O.

CAS number.

26807-65-8.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes