Consumer medicine information

Indapamide Sandoz Tablets

Indapamide hemihydrate

BRAND INFORMATION

Brand name

Indapamide Sandoz Tablets

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Indapamide Sandoz Tablets.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Indapamide Sandoz.

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

All medicines have risks and benefits. Your doctor has weighed the risk of you taking this medicine against the benefits they expect it will have for you.

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

WHAT INDAPAMIDE SANDOZ IS USED FOR

You have been prescribed Indapamide Sandoz for high blood pressure.

Indapamide Sandoz contains the active ingredient indapamide hemihydrate which belongs to a group of medicines called chlorosulphamoyl diuretics (a type of "fluid" or "water").

Indapamide Sandoz is available only with a doctor's prescription.

There is no evidence that Indapamide Sandoz is addictive.

Why Indapamide Sandoz 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) which is 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.

Indapamide Sandoz helps to lower your blood pressure.

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

BEFORE YOU TAKE INDAPAMIDE SANDOZ

There are some people who should not take Indapamide Sandoz. Please read the lists below. If you think any of these situations apply to you, or you have any questions, please consult your doctor or pharmacist.

When you must not take it

Do not take Indapamide Sandoz if:

  • You are allergic to indapamide, or any of the other ingredients of Indapamide Sandoz listed at the end of this leaflet.
  • You are allergic to sulphonamide (sulpha) antibiotics, or to thiazide diuretics (a type of "fluid" or "water" tablet).
  • You are pregnant or trying to become pregnant.
  • You are breastfeeding or plan to breastfeed.
  • You 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.
  • The packaging is torn or shows signs of tampering, or the tablets do not look quite right.

Before you start to take it

Tell your doctor straight away if:

  • You have an intolerance to lactose.
  • 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.
    - 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.

Taking other medicines

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

Taking Indapamide Sandoz may change the effect of some medicines, and some medicines may affect how well Indapamide Sandoz works. You may need different amounts of your medication or to take different medicines.

You should not take Indapamide Sandoz 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.

The medicines that may interact with Indapamide Sandoz include the following:

  • Some steroid medicines.
  • Diuretics (sometimes called "fluid" or "water" tablets).
  • Some medications used to treat high blood pressure, a fast or irregular heartbeat and other heart conditions.
  • Medicines to treat mental illnesses such as some medicines for epilepsy, anxiety, schizophrenia and some other antidepressants.
  • 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).
  • Cyclosporin, tacrolimus (medicines used to treat certain problems with the immune system).
  • Amphotericin B by IV, erythromycin by IV (antibiotic medicines used to treat infections).
  • Medicines used during scans to see the images of your body.
  • Diphemanil (used to treat excessive sweating).
  • Moxifloxacin (an antibiotic medicine used to treat infections).
  • Pentamidine (a medicine used to treat certain types of pneumonia).
  • Allopurinol (a medicine used to treat gout)

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

For older people or children

  • Elderly people can generally use Indapamide Sandoz safely. However, some older people have reduced kidney function - in which case additional care may be required.
  • Indapamide Sandoz is not recommended for use in children

HOW TO TAKE INDAPAMIDE SANDOZ

Follow all directions given to you by your doctor or pharmacist carefully. If you do not understand the instructions, ask your doctor or pharmacist for help.

Your doctor will select a dose when they prescribe Indapamide Sandoz for you. The usual dose is one tablet once daily.

Swallow your tablet with water, preferably in the morning. Do not crush or break them.

How long to take Indapamide Sandoz

Indapamide Sandoz can help to control your blood pressure, but cannot cure it. Indapamide Sandoz treatment is usually for life - so you should keep taking the tablets regularly unless advised otherwise by your doctor.

If you forget to take it

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

If your next dose is more than 6 hours away, take the dose you have missed as soon as you realise. Then take the next dose at the usual time and continue as normal.

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

If you take too much (overdose)

Taking too much Indapamide Sandoz (an overdose) may cause low blood pressure (also known as hypotension). Other effects like sickness, cramps, sleepiness, confusion, kidney problems, salt and water disturbances are possible. You may require urgent medical attention.

If you think that you or anyone else may have taken too much Indapamide Sandoz then act immediately

  • Telephone your doctor or the Poisons Information Centre (13 11 26 in Australia), or go to the Accident and Emergency department at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

WHILE YOU ARE TAKING INDAPAMIDE SANDOZ

Things you must do

Take Indapamide Sandoz exactly as your doctor has prescribed. Otherwise you may not get the benefits from treatment.

Tell all doctors, dentists and pharmacists who are involved with your treatment that you are taking Indapamide Sandoz.

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 Indapamide Sandoz as these may affect how Indapamide Sandoz 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 heart beat

Things you must not do

Do not take Indapamide Sandoz 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 lower the dosage without checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how Indapamide Sandoz affects you.

You may feel light-headed or dizzy when you begin to take Indapamide Sandoz. This is because your blood pressure is falling. Symptoms are likely to be made worse if you drink alcohol or take strong pain killers.

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.

Indapamide Sandoz may cause your skin to become more sensitive to the sun. If this happens you should stop taking Indapamide Sandoz 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 Indapamide Sandoz.

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

Indapamide Sandoz helps most people with high blood pressure, but it may sometimes have unwanted side effects. These can include:

  • 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 pain, back pain, joint pain, cramp or tingling or numbness of the hands or feet.
  • 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 potassium 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 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 heart beat.
  • Blurred or changed vision.
  • Dry mouth.
  • Cystitis

Most of these side effects are mild when they occur. Do not be alarmed by the following lists of 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.

If any of the signs below occur then tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital:

  • 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 heart beat.
  • Severe blisters, skin rash, itching or other allergic reactions.

These side effects are extremely rare but can become serious.

AFTER TAKING INDAPAMIDE SANDOZ

Storage

Keep your tablets in the pack until it is time to take them. Keep them in a cool, dry place where it stays below 25°C. Keep them where children cannot reach them.

Disposal

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

PRODUCT DESCRIPTION

What it looks like

Indapamide Sandoz 2.5mg - white, round, biconvex, sugar-coated tablets.

Available in blisters of 90 tablets.

Ingredients

Active ingredient:

  • Indapamide Sandoz 2.5mg - 2.5mg of indapamide hemihydrate.

Inactive ingredients:

  • lactose monohydrate
  • povidone
  • starch
  • maize
  • magnesium stearate
  • Opaseal clear P-2-0300G (ethyl acetate, stearic acid, polyvinyl acetate phthalate, purified water, industrial methylated spirit 74 OP)
  • purified talc
  • calcium carbonate
  • acacia
  • titanium dioxide
  • sucrose
  • Opaglos 6000P off-white (shellac, industrial methylated spirit 74 OP, beeswax white, carnuba wax).

This medicine does not contain gluten, tartrazine or any other azo food dyes.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park NSW 2113
Australia
Tel: 1800 634 500

This leaflet was revised in June 2015.

Australian Register Number
2.5mg film-coated tablet: AUST R 169291 (blister)

BRAND INFORMATION

Brand name

Indapamide Sandoz Tablets

Active ingredient

Indapamide hemihydrate

Schedule

S4

 

Name of the medicine

Indapamide hemihydrate.

Excipients.

Lactose monohydrate, maize starch, magnesium stearate, povidone, Opaseal P-2-0300G clear (ethyl acetate, stearic acid, polyvinyl acetate phthalate, purified water, industrial methylated spirit 74 OP), purified talc, calcium carbonate, acacia, titanium dioxide, sucrose and Opaglos 6000P off white (shellac, industrial methylated spirit 74 OP, beeswax white, carnauba wax).

Description

Chemical name: 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoyl benzamide hemihydrate. Melting point: approximately 185°C. Molecular formula: C16H16ClN3O3S.½H2O. CAS: 26 807-65-8. MW: 374.85.
Indapamide is a nonthiazide 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.
The excipient ingredients in Indapamide Sandoz are lactose monohydrate, maize starch, magnesium stearate, povidone, Opaseal P-2-0300G clear (ethyl acetate, stearic acid, polyvinyl acetate phthalate, purified water, industrial methylated spirit 74 OP), purified talc, calcium carbonate, acacia, titanium dioxide, sucrose and Opaglos 6000P off-white (shellac, industrial methylated spirit 74 OP, beeswax white, carnauba wax).

Pharmacology

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 functionally anephric patients 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 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.

Pharmacokinetics.

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 some 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 elimination.

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 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 5mL/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.

Indications

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

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.
Hypokalaemia.

Precautions

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 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 indapamide 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 Pharmacokinetics and Precautions).

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 Interactions with Other Medicines).

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.

Indapamide Sandoz tablets contain lactose.
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 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 Adverse Effects and Overdosage). 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. 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 adrenocorticoptropic (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.

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.
Caution should be used when treating patients with severe hepatic disease to avoid metabolic alkalosis in cases of potassium depletion which may precipitate episodes of hepatic encephalopathy. Treatment with the diuretic must be stopped immediately if this occurs.
Orthostatic hypotension may occur and may be potentiated by alcohol, barbiturates, narcotics or concurrent therapy with other antihypertensives.
When indapamide is combined with other non diuretic 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. This should be considered when using indapamide.
Although an indapamide 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.

Indapamide may give a positive reaction in doping tests.

Use in children.

Safety and effectiveness have not been established.

Use in pregnancy.

(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 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.

Use in lactation.

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 sulphonamide-derived medicines and hypokalaemia might occur.

Impairment of fertility.

A reproduction 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.

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).

Effects on the ability to drive and operate machinery.

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.

Interactions

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

Combined use that are 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 Torsade de pointes include:
class Ia antiarrhythmics (e.g. disopyramide);
class III antiarrhythmics (e.g. amiodarone, sotalol);
some antipsychotics: phenothiazines (e.g. trifluoperazine), benzamides (e.g. amisulpride, sulpiride) and butyrophenones (e.g. droperidol, haloperidol);
others: diphemanil, erythromycin IV, pentamidine, moxifloxacin.
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 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 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 (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 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.

Digoxin.

Monitoring of plasma potassium and ECG is recommended due to the increased risk of hypokalaemia following co-administration of indapamide and digoxin.

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.

Cyclosporin, tacrolimus.

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

Corticosteroids, (systemic route).

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

Effects on laboratory tests.

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%.

Adverse 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. 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 (potassium supplementation may be required in up to 25% of cases), after 4 to 6 weeks of treatment. After 12 weeks treatment, the mean fall in plasma potassium was 0.23 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 non-specific. Cutaneous rash and impotence have been occasionally reported. Percentages shown below indicate the incidence in clinical trials.
The following undesirable 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).

Blood and the lymphatic system disorders.

Very rare: thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia, haemolytic anaemia.

Metabolism and nutrition disorders.

Very rare: hypokalaemia.
Not known: potassium depletion with hypokalaemia, particularly serious in certain high risk populations (see Contraindications and Precautions sections).
Hyponatraemia+ (see Precautions section).

Nervous system disorders.

Common: dizziness, headache, fatigue, asthenia.
Uncommon: drowsiness, sleepiness, insomnia, weakness, anxiety.
Rare: vertigo, paresthesia.
Not known: syncope*.

Eye disorders.

Uncommon: visual impairment*.
Not known: myopia*, blurred vision*.

Cardiac disorders.

Very rare: arrhythmia, palpitations, chest pain.
Not known: torsade de pointes (potentially fatal) (see Precautions and Interactions with Other Medicines sections).

Gastrointestinal disorders.

Uncommon: vomiting, dyspepsia, abdominal pain.
Rare: nausea, constipation, dry mouth.
Very rare: pancreatitis.

Hepato-billiary disorders.

Very rare: abnormal hepatic function.
Not known: hepatitis*, possibility of onset of hepatic encephalopathy in case of hepatic insufficiency* (see Contraindications and Precautions).

Skin and subcutaneous tissue disorders.

Common: hypersensitivity reactions, mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions, maculopapular rashes.
Uncommon: purpura, pruritus.
Very rare: angioedema, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome (see Precautions).
Not known: possible worsening of pre-existing acute disseminated lupus erythematosus, photosensitivity reactions* (see Precautions section).

Musculoskeletal disorders.

Common: muscle cramps.

Renal and urinary disorders.

Uncommon: cystitis.
Very rare: renal failure.

Vascular disorders.

Very rare: hypotension.

Investigations.

Not known: electrocardiogram QT prolonged* (see Precautions and Interactions with Other Medicines); blood glucose increased*^; blood uric acid increased*^ (see Precautions); elevated liver enzyme levels.
+ Reported in clinical studies with the immediate release formulation of indapamide, and not seen in indapamide SR studies.
* Reported for indapamide as a Post-Marketing Adverse Effect.
^ Appropriateness of treatment with indapamide must be very carefully weighed in patients with gout or diabetes.
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.

Musculoskeletal.

Joint pain, back pain, weakness of legs.

Cardiac disorders.

Tachycardia, ECG changes (non specific 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.

Postmarketing experience, frequency unknown.

Metabolism and nutrition disorder.

Potassium depletion with hypokalaemia, particularly serious in certain high risk populations (see Contraindications and Precautions). Hyponatraemia with hypovolaemia responsible for dehydration and orthostatic hypotension. Concomitant loss of chloride ions may lead to secondary compensatory metabolic alkalosis: the incidence and degree of this effect are slight.

Nervous system disorders.

Syncope.

Eye disorders.

Myopia, blurred vision, visual impairment.

Cardiac disorders.

Torsade de pointes (potentially fatal) (see Contraindications and Interactions with Other Medicines).

Hepato-biliary disorders.

Possibility of onset of hepatic encephalopathy in case of hepatic insufficiency (see Precautions), hepatitis.

Skin and subcutaneous tissue disorders.

Possible worsening of pre-existing acute disseminated lupus erythematosus. Cases of photosensitivity reactions have been reported (see Precautions).

Investigations.

Electrocardiogram QT prolonged (see Precautions and Interactions with Other Medicines). Elevated liver enzyme levels. Blood glucose increased and blood uric acid increased during treatment: appropriateness of these diuretics must be very carefully weighed in patients with gout or diabetes.

Dosage and Administration

Adults.

One indapamide 2.5 mg tablet 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 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 one tablet (2.5 mg) of indapamide 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, 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.

Overdosage

Contact the Poisons Information Centre on 131 126 for advice on the management of overdose.
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.

Presentation

White, biconvex, sugar coated tablets, containing 2.5 mg indapamide hemihydrate. Available in blister packs of 60's* and 90's.
*Not currently marketed in Australia.

Storage

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

Poison Schedule

S4.