Consumer medicine information

Dapa-Tabs

Indapamide hemihydrate

BRAND INFORMATION

Brand name

Dapa-Tabs

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Dapa-Tabs.

What is in this leaflet

This leaflet answers some common questions about DAPA-TABS.

It is not to be used in relation to any other product, which may also contain the same active ingredient.

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

All medicines have benefits and risks. Your doctor has weighed the risks of you taking DAPA-TABS against the benefits expected for you.

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

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

What DAPA-TABS is used for

DAPA-TABS is used either alone or in combination with other medicines in the treatment of high blood pressure (hypertension).

DAPA-TABS contains the active ingredient indapamide hemihydrate, which belongs to a group of medicine called chlorosulphamoyl diuretics (a type of "fluid" or "water" tablet).

Why DAPA-TABS is used for high blood pressure

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 (also known as 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.

DAPA-TABS helps to lower blood pressure.

Ask your doctor if you have any questions about why DAPA-TABS has been prescribed for you. Your doctor may have prescribed DAPA-TABS for another purpose.

DAPA-TABS is not recommended for use in children, as its safety and effectiveness in children have not been established.

DAPA-TABS is available only with a doctor's prescription.

There is no evidence that DAPA-TABS is addictive.

Before you take DAPA-TABS

When you must not take it

Do not take DAPA-TABS if you have an allergy to:

  • medicines containing indapamide.
  • sulfonamide or sulfa (sulpha) antibiotics, or thiazide diuretics (a type of "fluid" or "water" tablet).
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.

Do not take DAPA-TABS if you have:

  • severe liver disease or if you suffer from a condition called hepatic encephalopathy, a liver problem which affects the brain and central nervous system.
  • severe kidney problems such as anuria or progressive and severe oliguria.
  • low potassium levels in your blood.

Do not take DAPA-TABS if you are pregnant or plan to become pregnant. There is no information on the use of DAPA-TABS in pregnancy. Therefore, DAPA-TABS is not recommended for use in pregnant women. Medicines of this type have been associated with unwanted effects in the unborn baby.

Do not take DAPA-TABS if you are breastfeeding or plan to breastfeed. DAPA-TABS is not recommended for use in breastfeeding women, as it is not known whether this medicine passes into breast milk and how it may affect your baby.

Do not take DAPA-TABS if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date, it may not work as well.

Do not take DAPA-TABS if the packaging shows signs of tampering or the tablets do not look quite right.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you have an intolerance to lactose.

Tell your doctor if you have any medical conditions, especially the following:

  • high or low levels of potassium, sodium, or other problems with salt balance
  • systemic lupus erythematosus (SLE), a disease affecting the skin, joints and kidneys
  • gout
  • diabetes
  • you have previously experienced an increased sensitivity to sunlight (photosensitivity reactions)
  • heart rhythm problems
  • kidney problems
  • liver problems.
  • 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 DAPA-TABS. This can lead to permanent vision loss, if not treated. If you have 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.

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if have done or are planning to do 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.

If you have not told your doctor about any of the above, tell them before you start taking DAPA-TABS.

Taking other medicines

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

Some medicines may be affected by DAPA-TABS, or may affect how well it works. These include:

  • lithium, a medicine used to treat mood swings and some types of depression, due to the risk of increased levels of lithium in the blood
  • medicines used to treat mental illnesses such as some medicines for epilepsy, anxiety, schizophrenia and some other antidepressants (e.g.citalopram, escitalopram. tricyclic antidepressants, antipsychotic drugs, neuroleptics such as: droperidol, haloperidol, chlorpromazine, trifluoperazine, amisulpride, sulpiride, psychoanaleptics).
  • antiparasitic medicines used to treat certain types of malaria (e.g. chloroquine phosphate).
  • other medicines used to treat high blood pressure (e.g. angiotensin converting enzyme (ACE) inhibitors), a fast or irregular heartbeat and other heart conditions.
  • other diuretics, also known as "water" or "fluid" tablets (e.g. amiloride, spironolactone, triamterene).
  • medicines used for heart rhythm problems (e.g. disopyramide, amiodarone hydrochloride, sotalol hydrochloride, flecainide acetate)
  • barbiturates, medicines used to treat epilepsy, produce calmness or to help you sleep
  • medicines used to treat Alzheimer's disease, for example, donepezil
  • non-steroidal anti-inflammatory drugs for pain relief (e.g. ibuprofen) or high doses of aspirin
  • corticosteroids, medicines used in the treatment of conditions such as allergic reactions, asthma, inflammatory and 'auto-immune' diseases
  • strong pain killers
  • 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
  • amphotericin B (amphotericin) by IV, erythromycin by IV, clarithromycin (antibiotic medicines used to treat infections)
  • medicines used to treat fungal infections, for example, fluconazole
  • medicines used during scans to see the images of your body
  • diphemanil metisulfate (used to treat excessive sweating)
  • pentamidine isetionate (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).
  • anagrelide (used to reduce elevated blood platelet counts)
  • medicines used to treat gastrointestinal problems (e.g. cisapride, papaverine hydrochloride)
  • medicines used to treat bacterial infections (e.g. Moxifloxacin, ciprofloxacin, clarithromycin, erythromycin by IV).
  • allopurinol (a medicine used to treat gout).
  • tetracosactide (tetracosactrin) (to treat Crohn’s disease)
  • methadone hydrochloride (used to treat addiction).
  • cilostazol (used to treat cramp-like pain in the legs when you walk).

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking DAPA-TABS.

For older people or children

Elderly people can generally use DAPA-TABS safely. However, some older people have reduced kidney function- in which case additional care may be required.

DAPA-TABS is not recommended for use in children.

How to take DAPA-TABS

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist.

How much to take

The usual adult dose is one tablet daily, taken in the morning.

How to take DAPA-TABS

Swallow the tablets whole with a glass of water.

When to take DAPA-TABS

Take DAPA-TABS at about the same time each morning.

DAPA-TABS can be taken with or without food.

If you forget to take it

If your next dose is less than 6 hours away, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

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

If you are not sure what to do, ask your doctor or pharmacist.

How long to take it for

To properly control your blood pressure, DAPA-TABS must be taken every day.

Keep taking DAPA-TABS for as long as your doctor recommends.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much DAPA-TABS.

Do this even if there are no signs of discomfort or poisoning.

Taking too much DAPA-TABS (an overdose) may cause low blood pressure (hypotension). Other effects like sickness, cramps, sleepiness, confusion, kidney problems, salt and water disturbances are possible.

You may need urgent medical attention.

While you are taking DAPA-TABS

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking DAPA-TABS.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking DAPA-TABS.

If you become pregnant while taking DAPA-TABS, tell your doctor immediately.

Visit your doctor regularly for check-ups. Your doctor may want to check your blood pressure, kidney function, sodium levels and potassium levels while you are taking DAPA-TABS.

If you have to have any other blood tests, tell your doctor that you are taking DAPA-TABS. DAPA-TABS may affect the results of some tests.

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 straight away if you have excessive vomiting or diarrhoea while taking DAPA-TABS as these may affect how DAPA-TABS is processed by your body. If you experience any of the following symptoms, you may be dehydrated because you are losing too much water:

  • dry mouth or thirst
  • fainting
  • weakness
  • tiredness or drowsiness
  • muscle pain or cramps
  • fast heartbeat
  • passing less urine than normal

Things you must not do

Do not stop taking DAPA-TABS or change the dose without checking with your doctor.

Do not let yourself run out of DAPA-TABS over weekends or on holidays.

Do not use DAPA-TABS to treat any other conditions unless your doctor tells you to.

Do not give DAPA-TABS to anyone else, even if they have the same condition as you.

Things to be careful of

Be careful driving or operating machinery until you know how DAPA-TABS affects you. DAPA-TABS may cause tiredness, dizziness, or light-headedness in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous.

Dizziness or light-headedness may be worse if you drink alcohol, take strong pain killers, barbiturates or other medicines for high blood pressure while being treated with DAPA-TABS.

Be careful getting up from a sitting or lying position. Dizziness, light-headedness, or fainting may occur, especially when you get up quickly. Getting up slowly may help.

Make sure you drink enough water in hot weather and during exercise when you are taking DAPA-TABS, especially if you sweat a lot.

Also make sure you tell your doctor if you become sick and have severe or continuing vomiting or diarrhoea while taking DAPA-TABS.

The loss of additional water and certain salts such as potassium from the body may make you feel faint, lightheaded, weak or sick.

DAPA-TABS may cause your skin to become more sensitive to the sun. If this happens you should stop taking DAPA-TABS and contact your doctor.

If you have these symptoms and they don't get better in a short time, then talk to your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking DAPA-TABS. DAPA-TABS helps most people to lower their high blood pressure but it may have unwanted side effects in some people.

All medicines can 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 to answer any questions you may have.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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

  • feeling sick or stomach upset, having an uncomfortable feeling after eating, vomiting, constipation, diarrhoea, or loss of appetite
  • unusual tiredness or weakness, difficulty sleeping
  • 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
  • an increased risk of becoming dehydrated (in elderly patients and in patients with heart failure)
  • dizziness or lightheaded-ness or feeling faint, especially when getting up from a sitting or lying position
  • feeling nervous or anxious
  • headache
  • diarrhoea, constipation
  • gout
  • increased sensitivity to sunlight
  • low potassium, magnesium or chlorine levels. Symptoms of low potassium can include a number of those listed above, and very occasionally this may be severe
  • kidney disease
  • inflammation of the pancreas
  • hepatic encephalopathy (liver problems which affect the brain and the central nervous system)
  • abnormal liver function
  • if you suffer from systemic lupus erythematous (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).
  • high level of calcium in blood
  • low blood pressure, unusual heartbeat
  • 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

Most of these side effects are mild when they occur. Do not be alarmed by this list of possible side effects. You may not experience any of them. However if you do - or if you notice anything else that is making you feel unwell - you should consult your doctor or pharmacist.

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, magnesium, chloride or 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.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • signs of an allergic reaction such as skin rash, itching or hives; swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing; wheezing or shortness of breath.
  • 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.
  • 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 DAPA-TABS. This can lead to permanent vision loss, if not treated. If you have a penicillin or sulfonamide allergy, you can be at higher risk of developing this.

The side effects listed above are serious and require urgent medical attention or hospitalisation.

Tell your doctor if you notice anything that is making you feel unwell.

This is not a complete list of all possible side effects.

Other side effects not listed above may also occur in some people. Also, some of side effects can only be found when your doctor does tests from time to time to check your progress.

After using DAPA-TABS

Storage

Keep DAPA-TABS 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 your tablets in the pack until it is time to take them. If you take the tablets out of the pack they will not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store DAPA-TABS or any other medicine in the bathroom or near a sink.

Do not leave DAPA-TABS in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking DAPA-TABS, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

DAPA-TABS is a 6.5 mm, normal convex, pink, film-coated tablet debossed "IE" over "2.5" on one side and "G" on the other.

Each pack contains 90 tablets.

Ingredients

The active ingredient in DAPA-TABS is indapamide hemihydrate.

Each tablet contains 2.5 mg of indapamide hemihydrate.

The tablets also contain the following inactive ingredients:

  • lactose
  • microcrystalline cellulose
  • sodium starch glycollate
  • croscarmellose sodium
  • magnesium stearate
  • Opadry Pink OY-6953 (ARTG PI No. 3110).

DAPA-TABS tablets contain lactose and trace quantities of sulfites.

Manufacturer

DAPA-TABS is made in Australia by:

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

Australian registration number:

DAPA-TABS - AUST R 62367

This leaflet was prepared in May 2022.

DAPA-TABS® is a Viatris company trade mark.

DAPATABS_cmi\May22/00

Published by MIMS June 2022

BRAND INFORMATION

Brand name

Dapa-Tabs

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

1 Name of Medicine

Indapamide hemihydrate.

2 Qualitative and Quantitative Composition

Each Dapa-Tabs tablet contains 2.5 mg of indapamide hemihydrate as the active ingredient.

Excipients with known effect.

Lactose and trace quantities of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Dapa-Tabs (indapamide hemihydrate) 2.5 mg tablets: 6.5 mm, normal convex, pink, film coated tablet debossed "IE" over 2.5 on one side, and "G" on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of hypertension. It may be tried as a sole therapeutic agent in the treatment of hypertension. Normally indapamide is used as the initial agent in multiple drug regimens.

4.2 Dose and Method of Administration

Adults.

1 tablet (2.5 mg indapamide hemihydrate) to be taken daily, by oral route, in the morning. The action of indapamide is progressive and whilst the optimum reduction in blood pressure is usually seen after 4 weeks, a further small but useful reduction in blood pressure may be observed over the following 4 to 6 weeks. A larger dose than one tablet (2.5 mg) of Dapa-Tabs daily is not recommended as there is little additional antihypertensive effect, whilst the diuretic effect becomes more pronounced.
A single daily tablet of indapamide may effectively be combined with the following antihypertensive medicines: beta-blockers, methyldopa sesquihydrate, clonidine, prazosin and 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 1 or 2 weeks after the treatment is stopped.

4.3 Contraindications

Dapa-Tabs is contraindicated in:
severe renal failure, anuria, progressive and severe oliguria;
hepatic coma, hepatic encephalopathy or severe impairment of liver function;
known hypersensitivity to indapamide, to 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 hemihydrate is 2.5 mg administered as one tablet, since doses above 2.5 mg only increase the diuretic effect and electrolyte disturbances 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 Dapa-Tabs 2.5 mg 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 and below subheadings).

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 treatment with indapamide, and gout has been reported rarely. 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 readministration of the diuretic is deemed necessary, it is recommended that areas exposed to the sun or to an artificial UVA are protected.

Lactose intolerance.

Dapa-Tabs contain lactose.
Patients with an intolerance to lactose, rare hereditary problems of galactose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Water and electrolyte imbalance.

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 also be assessed during treatment.
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 indapamide 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 with sulfonamides. This should be considered when using indapamide.
Although a Dapa-Tabs dose of one 2.5 mg tablet/day can be used safely in patients with hypertension and renal impairment, the 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.

Dapa-Tabs 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 Dapa-Tabs when renal function is normal or only minimally impaired.
See Section 4.4 Special Warnings and Precautions for Use, Plasma sodium and Plasma potassium above.

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 pretreatment 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%.
Also see Section 4.4 Special Warnings and Precautions for Use, Athletes above.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interactions have been reported between indapamide and anticoagulants, or between indapamide and uricosurics medicines. It is recommended that indapamide not be used in combination with a diuretic since the combination may cause hypokalaemia and hyperuricaemia.

Combined use which is not recommended.

Lithium.

The combined use of indapamide 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 indapamide 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 antiarrhythmic agents (e.g. disopyramide) and class Ic antiarrhythmic agents (e.g. flecainide acetate);
class III antiarrhythmic agents (e.g. amiodarone hydrochloride, sotalol hydrochloride);
some antipsychotics: phenothiazines (e.g. chlorpromazine, trifluoperazine), benzamides (e.g. amisulpride, sulpiride) and 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 phosphate, pentamidine isetionate);
antihistamines;
antiemetics (e.g. ondansetron, domperidone);
antineoplastic and immunomodulating agents (e.g. vandetanib, oxaliplatin, anagrelide);
anaesthetics (e.g. propofol, sevoflurane);
others: diphemanil metilsulfate, methadone hydrochloride, papaverine hydrochloride, cilostazol.
This list is indicative and not exhaustive.
Monitor (using plasma electrolytes and ECG) for hypokalaemia and correct if required, before using indapamide and a Torsades de pointes inducing drug in combination.

NSAIDs (systemic route) including COX-2 selective inhibitors, high dose acetylsalicylic 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 indapamide.

Angiotensin converting enzyme (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 mineralo-corticoids (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 nonstimulant 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 coadministering potassium sparing diuretics. Plasma potassium and ECG should be monitored and, if necessary, treatment reviewed.

Metformin.

Do not coadminister 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 thrombocytopaenia 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, medicines of this type should be used with caution and at the lowest effective dose.
 Indapamide should not be used during breastfeeding. 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: hypokalaemia, hypersensitivity reactions, mainly dermatological (in subjects with a predisposition to allergic and asthmatic reactions and maculopapular rashes), asthenia, dizziness, headache, fatigue, muscle cramps and gastrointestinal disturbances. These usually occur 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 4 to 6 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 (≥ 1/1000, < 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, and not seen in the indapamide SR studies, 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 the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at 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 care. 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 1 or 2 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 medicine. 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 patients who are functionally anephric lends support to this 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 man. 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.
Indapamide is a non-thiazide indole derivative of chlorosulfonamide.

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 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 14C, 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

Sodium starch glycollate, magnesium stearate, microcrystalline cellulose, lactose, croscarmellose sodium, Opadry Pink OY-6953 (ARTG PI No. 3110).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. For further information, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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 30°C.

6.5 Nature and Contents of Container

Dapa-Tabs: PVC/PVDC/Al blister packs of 30, 60 or 90 tablets.
Some pack sizes may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 62367 - Dapa-Tabs indapamide hemihydrate 2.5 mg tablet blister pack.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Structural formula:
Chemical name: 4-chloro-N-[(2RS)-2- methyl-2,3-dihydro-1H- indol-1-yl]- 3-sulfamoylbenzamide hemihydrate.
Molecular formula: C16H16ClN3O3S.½H2O. Molecular weight: 374.85.
Indapamide 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.
Melting point is approximately 185°C.

CAS number.

26807-65-8.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes